Tremendous new development and changes are seen in the lung cancer treatment for the past 2-3 years. This lecture covers the most updated information and treatment of lung cancer.
Thank you so much igho for your full dedication am very happy and proud to come across your TH-cam channel. Your medications is indeed incomparable, my four years cancer disappeared completely within 15 days of usage and without any side effects, keep saving lives doctor.
I have stage 4 nsclc. I was dx December 2019. Exactly 4 years ago. First 6 treatments Keytruda/carbo/alimta (spelling is bad lol). Then went to Keytruda/alimta til August 2021. Keytruda affected my adrenal gland and thyroid. But doing well. I have just ended alimta lady month due to neurological and other side effects. But, I am still here, working and figuring out my new normal. Just did the blood work for Signatera and waiting results. My scans show only scaring now. Mets to adrenal gland is stable, Mets lymph nodes all around neck and obstruction to trechea and chest , ned😁. Thanks for your video! Very interesting. I am very curious to what the new stats show for survival. I believe it will show a huge difference.
Hello , My Father has Stage 4 a lung cancer with local lung metastasis. Currently have started carboplatin and pemetrexed. Awaiting results pf Genome reports . But he is very healthy and active even after one cycle of chemo , (touch wood) but I am very much terrified. Please pray for him and give me some hope to stay positive as he is my only reason for my survival 😭
For EGFR (+) non small cell lung cancer, anti-EGFR TKI drugs such as gefitinib (but osimertinib is more preferred) are used alone without chemotherapy. But some studies showed combination of anti-EGFR TKI and chemotherapy may be effective. Good luck and God bless the patient!
In October of 2023I was diagnosed with nsc stage 4 lung cancer which spread to the brain. I was in the hospital for three weeks and had ten rounds on brain radiation. In December i started chemo and immunotherapy. I just finished my sixth treatment last week. I'm taking Keytruda, Alimta and Carboplatin. I went for a MRI and CT scan in February and the oncologist had good news for me. Everything is shrinking and there is no new growth and nothing is spreading. Now I'm taking Keytruda and Alimta for the next 12 months after that it will just be Keytruda for the next 12 months after that. I've had no major side effects other than slight change in taste and slight appetite change. I'm still eating but not the same foods as before. I'm hoping for continued success with this treatment. The nodule they originally found on my right lung in October was 1.5cm.
I hope your treatments continue to work. You are very brave to fight so hard. I have stage 3B large cell neuroendocrine lung cancer and have finished all possible chemo and rads to try to stop it.. Hoping very hard for slow spread.... (good response but not remission of course with this cancer). Very best to you in your fight. I think there are many of us together in this.
Victor. Your story is similar to mine. I am taking Zepzelca chemo once a month at the lowest dose. I’m only taking it as a precaution for no reoccurrence even though I could quit all together as I’m cancer free . You won’t believe me .. but my cancer went dormant as soon as I started taking Fenbendezol. It’s a dog dewormer. Crazy I know. But I was given 6 months and I’m here 3 years later. Joe Tippens Protocol. If treatment fails for you.. look it up. Good luck!
The US Food and Drug Administration has granted accelerated approval to tarlatamab-dlle (Imdelltra, Amgen) for extensive-stage small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy. Tarlatamab is a first-in-class bispecific T-cell engager (BiTE) that binds delta-like ligand 3 on the surface of cells, including tumor cells, and CD3 expressed on the surface of T-cells. It causes T-cell activation, release of inflammatory cytokines, and lysis of DLL3-expressing cells, according to labeling. Approval was based on data from 99 patients in DeLLphi-301 trial with relapsed/refractory extensive-stage SCLC who had progressed after platinum-based chemotherapy Patients with symptomatic brain metastases, interstitial lung disease, noninfectious pneumonitis, and active immunodeficiency were excluded. The overall response rate was 40%, and median duration of response 9.7 months. The overall response rate was 52% in 27 patients with platinum-resistant SCLC and 31% in 42 with platinum-sensitive disease. Continued approval may depend on verification of clinical benefit in a confirmatory trial. Labeling includes a box warning of serious or life-threatening cytokine release syndrome and neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome. The most common adverse events, occurring in 20% or more of patients, were cytokine release syndrome, fatigue, pyrexia, dysgeusia, decreased appetite, musculoskeletal pain, constipation, anemia, and nausea. The most common grade 3 or 4 laboratory abnormalities included decreased lymphocytes, decreased sodium, increased uric acid, decreased total neutrophils, decreased hemoglobin, increased activated partial thromboplastin time, and decreased potassium. The starting dose is 1 mg given intravenously over 1 hour on the first day of the first cycle followed by 10 mg on day 8 and day 15 of the first cycle, then every 2 weeks until disease progression or unacceptable toxicity.
New bispecific T cell Engager (BiTE) for SCLC In May 2024, the FDA has granted accelerated approval to tarlatamab-dlle (Imdelltra, Amgen) for extensive-stage small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy. Tarlatamab is a first-in-class bispecific T-cell engager (BiTE) that binds delta-like ligand 3 on the surface of cells, including tumor cells, and CD3 expressed on the surface of T-cells. It causes T-cell activation, release of inflammatory cytokines, and lysis of DLL3-expressing cells. Approval was based on data from 99 patients in DeLLphi-301 trial with relapsed/refractory extensive-stage SCLC who had progressed after platinum-based chemotherapy Patients with symptomatic brain metastases, interstitial lung disease, noninfectious pneumonitis, and active immunodeficiency were excluded. The overall response rate was 40%, and median duration of response 9.7 months. The overall response rate was 52% in 27 patients with platinum-resistant SCLC and 31% in 42 with platinum-sensitive disease. Continued approval may depend on verification of clinical benefit in a confirmatory trial. Labeling includes a box warning of serious or life-threatening cytokine release syndrome and neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome. The most common adverse events, occurring in 20% or more of patients, were cytokine release syndrome, fatigue, pyrexia, dysgeusia, decreased appetite, musculoskeletal pain, constipation, anemia, and nausea. The most common grade 3 or 4 laboratory abnormalities included decreased lymphocytes, decreased sodium, increased uric acid, decreased total neutrophils, decreased hemoglobin, increased activated partial thromboplastin time, and decreased potassium. The starting dose is 1 mg given intravenously over 1 hour on the first day of the first cycle followed by 10 mg on day 8 and day 15 of the first cycle, then every 2 weeks until disease progression or unacceptable toxicity.
EGFR 20 mutated NSCLC can be treated with afatinib. Recent FDA approval of 2 other drugs include: Mobocertinib - is a single molecule that binds to the EGFR protein within Exon 20 cancer cells and blocks growth signaling within the cell. Amivantamab - is a monoclonal anti-body that binds on the EGFR protein and blocks signaling to the protein in Exon 20 cells and calls in the body’s immune system for additional support.
Mobocertinib was withdrawn from the market as of October 2023 as it did not fulfill the goal as a mono therapy for EGFR axon 20 insertion mutation: no benefit in overall survival.
Thanks for reaching for help I from Cape town South Africa my husband died November 2023 he was diagnosed with COVID pneumonia reading his biopsy results he had lung cancer he was diagnosed by pulmonigist at a private hospital he smoke and his parents died of lung cancer his Dr refuse to show me his full blood count results and diff count results I am a medical results officer 28 years don't know treatment but can read results I would like to to get closer for our children he lived on oxygen private hospital and Dr's don't know how hard it is family I expect it but not the children how many private hospital and Dr's pulmonigist take a a oath for granted bless you
New NCCN guidelines were added for NSCLC 2023 But these are already discussed in my presentation. In fact, these NCCN guidelines have been approved by FDA before. So it seems that the NCCN is following the FDA not preceding. Nevertheless the new NCCN guidelines have a few important points which were explained in detail. 1. Neoadjuvant immunochemothetapy: For the 2023 update (Version 1.2023), the NCCN panel added a recommendation that patients should be evaluated for perioperative (neoadjuvant or adjuvant) therapy before surgery. The panel recommends nivolumab + platinum-doublet chemotherapy as a neoadjuvant systemic therapy option for eligible patients with resectable (tumors ≥4 cm or node-positive) NSCLC based on clinical trial data and the FDA approval (see NSCL-E 1 of 3, page 349).20-22 For the 2023 update (Version 1.2023), the panel added a recommendation that all patients should be evaluated for neoadjuvant therapy, with strong consideration for patients with node-positive disease or tumors ≥4 cm and who have no contraindications for ICIs. Neoadjuvant therapy should not be used to attempt to induce resectability in patients who do not already meet criteria for resectability on initial evaluation. 2. Adjuvant targeted therapy: The NCCN panel recommends osimertinib as an adjuvant therapy option for eligible patients with completely resected (R0) stage IB (only T = 4 cm) to IIIA and stage IIIB (only T3N2)***EGFR mutation-positive ****NSCLC who have previously received adjuvant chemotherapy or are ineligible to receive platinum-based chemotherapy based on clinical trial data and the FDA approval. 3. Adjuvant immunotherapy after complete surgical resection: (1) Atezolizumab: The panel recommends atezolizumab as an adjuvant therapy option for eligible patients with PD-L1 levels ≥1% and completely resected stage IIB-IIIA, stage IIIB (only T3N2)***, or high-risk stage*IIA NSCLC who have previously received adjuvant chemotherapy based on clinical trial data and the FDA approval (1) Pembrolizumab** For the 2023 update (Version 2.2023), the panel added a recommendation for adjuvant pembrolizumab for eligible patients with completely resected (R0) stage IIB-IIIA, stage IIIB (only T3N2)***, or high-risk*stage IIA NSCLC who are negative for EGFR exon 19 deletions, EGFR exon 21 L858R mutations, or ALK fusions****and who have previously received adjuvant chemotherapy based on clinical trial data and the FDA approval. * High-risk factors may include poorly differentiated tumors, vascular invasion, wedge resection, visceral pleural involvement, and unknown lymph node status (Nx). **The panel added a caveat**that the benefit of adjuvant pembrolizumab is unclear for patients with PD-L1 levels
Your yellow highlighting during the lecture to tracks from your presentation because it's not clear if you can find out some way to highlight and yellow where it's clear where you can still read through the Highlight then it might be beneficial
Durvalumab (Imfinzi) administered sequentially as an adjuvant immunotherapy after platinum-based concurrent chemo radiation therapy (CRT) is already an established standard of care for the treatment of that type of lung cancer. But the so-called "PACIFIC-2 Phase 3" trial for durvalumab concurrently administered with CRT aimed to address patients who progress or discontinue treatment during CRT did not achieve statistical significance for progression-free survival versus CRT alone. The drug company (AstroZeneca) also said that there was an increased rate of infection during the concurrent treatment period in the experimental arm.
In August 2023, NCCN issued new guidelines regarding adjuvant therapy (immuno and targeted) for NSCLC. I must tell you that these recommendations have been presented in this TH-cam lecture already! The National Comprehensive Cancer Network (NCCN) issued new guidelines for the treatment and management of patients with non-small cell lung cancer. Published in the Journal of the National Comprehensive Cancer Network, the document concentrates on treatment options for patients with resectable disease in the neoadjuvant and adjuvant settings. In recent years, multiple new treatment options have become available for patients with NSCLC, corresponding to improvements in survival. The NCCN annually updates its guidelines for treatment to reflect advances in the field. The NCCN convened a panel of lung cancer experts to evaluate clinical data and offer up-to-date recommendations based on the best available evidence. In the neoadjuvant setting, the expert panel recommended that systemic therapy may be offered following surgical evaluation to patients who are likely to receive perioperative chemotherapy. Based on data from the CheckMate 816 study, they recommended treatment with nivolumab and platinum-doublet chemotherapy for patients with resectable NSCLC and no PD-L/PD-L1 contraindications. All patients should be evaluated to determine whether neoadjuvant therapy is an appropriate choice, according to the authors, although neoadjuvant therapy should not be used to prompt resectability in patients with unresectable tumors. Patients with node-positive disease and tumors 4 cm or greater in size should especially be considered for neoadjuvant therapy. Because treatment with immune checkpoint inhibitors carries the risk for severe immune-mediated adverse events, health care providers should be trained to recognize the onset of these conditions. Patients should discontinue nivolumab at the onset of severe or life-threatening pneumonitis. Based on data from the phase 3 ADAURA study, the experts recommended osimertinib as adjuvant systemic therapy for patients with complete resected stage IB-IIIA and stage IIIB (T3N2 only) EGFR-positive NSCLC who have received previous adjuvant chemotherapy or are ineligible for platinum-based chemotherapy. “Although it is technically easier to use a resected specimen for molecular testing, it is also acceptable to use initial diagnostic biopsy specimens,” the authors wrote. “However, plasma cell-free/circulating tumor DNA testing is not recommended in this setting, because tissue is available and it is difficult to detect mutations in peripheral blood in patients with early-stage disease. The NCCN Guidelines include a caveat that if patients have oncogenic driver mutations and high PD-L1 levels, they should receive appropriate targeted therapy, such as osimertinib, and not immune checkpoint inhibitors and not both.” Regarding immunotherapy, the panel endorsed atezolizumab as adjuvant therapy for patients with PD-L1 expression of 1% or greater and completely resected stage IIB-IIIA disease; completely resected stage IIIB disease (T3N2 only); or high-risk stage IIA disease with no EGFR exon 19 deletions, or exon 21 L858R mutations, or ALK fusions. For eligible patients with the same characteristics, the panel also recommended adjuvant pembrolizumab, based on data from the PEARLS/KEYNOTE 091 clinical trial. The panelists defined high-risk characteristics as poorly differentiated tumors, vascular invasion, wedge resection, visceral pleural involvement, and unknown lymph node status. They cautioned that data from the trial left unclear the benefit of pembrolizumab in patients with a PD-L1 expression below 1%. “Patients with ALK fusions, EGFR exon 19 deletions, or EGFR exon 21 L858R mutations have less benefit from immune checkpoint inhibitors,” the authors wrote. “Testing for PD-L1 status, EGFR mutations, and ALK fusions is recommended before administering atezolizumab or pembrolizumab as adjuvant therapy. For the 2023 update, the panel expanded the molecular testing criteria to include ALK fusions. Although it is technically easier to use a resected specimen for molecular testing, it is also acceptable to use initial diagnostic biopsy specimens.”
Neoadjuvant therapy with duevalumab and chemotherapy also showed improvement of event free survival. The pathological complete remission was also compatible with those with pembrolizumab (17%). NEJM published the final result in November 2033. I have described it in this lecture. www.nejm.org/doi/full/10.1056/NEJMoa2304875
New data showed that the bispecific antibody amivantamab (Rybrevant) combined with chemotherapy was better than chemotherapy alone in EGFR-mutated (axon 20 insertion) advanced non-small cell lung cancer (NSCLC). www.nejm.org/doi/pdf/10.1056/NEJMoa2306441 patients with EGFR exon 20 insertion-mutated advanced NSCLC. These patients, who represent about 2% to 3% of NSCLC cases, have "historically poor" outcomes, with a 5-year overall survival rate of just 8%. The FDA approved amivantamab in 2021 for EGFR exon 20 insertion-mutated advanced NSCLC after progression on platinum-based chemotherapy, but the PAPILLON trial explored whether combining the two therapies upfront would provide a more meaningful benefit. In the trial, 308 treatment-naïve patients with locally advanced or metastatic NSCLC and documented exon 20 insertions were randomly assigned to amivantamab plus chemotherapy or chemotherapy alone. The median age was about 62 years, approximately half were female, and just over 60% were Asian - a similar patient profile as MARIPOSA and MARIPOSA-2. It showed that amivantamab plus chemotherapy significantly increased progression-free survival (PFS). More specifically, after a median follow-up of 14.9 months, patients receiving the combination had a median PFS of 11.4 months vs 5.7 months with chemotherapy alone (hazard ratio [HR], 0.395; P < .0001). This benefit consistently occurred across predefined subgroups. Amivantamab plus chemotherapy was associated with a lower risk of a second progression, with the median not reached vs 17.2 months with chemotherapy alone (HR, 0.493; P = .001). A higher proportion of patients receiving the combination had an objective response -73% vs 47% - and these patients had a longer duration of response as well - 9.7 months vs 4.4 months. The overall survival data were immature but showed a trend toward a reduced risk of death for those on the combination (HR, 0.675; P = .106). The rates of grade ≥ 3 adverse events were 75% with amivantamab plus chemotherapy and 54% with chemotherapy alone, and adverse events leading to discontinuation of amivantamab occurred in 7% of patients. Pneumonitis/interstitial lung disease (ILD) was reported in 3% of patients in the combination therapy arm.
Thank you for this wonderful video. Would you be able to tell me if immunotherapy would be an option for a late stage cancer patient with an autoimmune disease (colitis)? If so what precautions would need to be taken and what symptoms would need to be looked out for?
Yes, you may. However, the side effects from the immunotherapy may be severe. Please watch my lecture “immunotherapy side effects. “posted on TH-cam. I wish you the best results and a quick recovery.
Dear Dr. Kim, I have stage 3B large cell neuroendocrine lung cancer. I finished chemo (5 rounds etoposide and carboplatin) and 6 weeks of concurrent radiation. I had good response to this but of course not total remission. Now the only thing I am being offered next is Imfinzi. I did not have any PD-L1 expression found on my tumor sample. I am told that I do not have any mutations or markers found for targeted therapy or immunotherapy. Do you think that Imfinzi makes any sense for me? I am of course desperate to do something besides waiting for my cancer to grow back and spread to other areas of my body. Thank you for your information here and any opinion you have for me.
I understand your question. Usually immunotherapy is effective for PD-L1 positive tumors. However, not always. For instance, small cell lung cancer responds better with combination of Imfinzi and chemotherapy even in PD-L1 negative small cell cancer. Imfinzi is well tolerated drug (pneumonitis can be serious side effect), and is used in a clinical trial, so I would not reject your oncologist’s suggestion. I sincerely hope your quick recovery.
@@stanleykim1924 Thank you so much for your reply. I do not want to risk the serious side effects if there is no hope of a response - but from all I have read it seems impossible to know. I still do not know what to do but I sincerely appreciate you taking the time to reply to me and I respect your answer. God bless you.
New Guidelines by ACS for lung cancer screening issued in November 2023: The new guidelines lowered the age for annual lung cancer screening among asymptomatic former or current smokers from 55-74 years to 50-80 years. The update also now considers a high-risk person anyone with a 20-pack-year history, down from a 30-pack-year history, and removes the requirement that former smokers must have quit within 15 years to be eligible for screening.
Hello, thank you for the extremely informative video. My husband has stsge 4 ALK postive. He has been taking steroids, and Alecensa for 6wks. Initially 2pills xtwice daily as he was so late to be diagnosed due to multiple false diagnosing then a very long waitfor pathology results. The oncologist thought he was too ill to cope with 3 pills as he was immobile due to extreme weight loss, agonising spinal pain, and low appetite. She had written him off. He has been on 3pills xtwice daily for 10days now with no side effects...so far. Hes becoming mobile again, albeit slow and with a stick. He is pain free due to pain relief patches and the steroids, and is gaining weight. Am i correct in reading/hearing that you said this treatment is 80% successful? Does this mean successful cure? Thank you Gill
80% response rate, not cure. But many patients who responded targeted therapy continue in remission many years. Also check for PD-L1 score. I wish him the best results and a long survival with you.
May I ask what kind of cancer you have? I have grown married girls and grandkids, I have put off telling them, I think they know just by guessing. I had stage 1 non small cell but it has went to stage 2 or 3 will know for sure in a few days. I have always said I did not want to make it to 80 years of age and I truly do not, I know sounds weird what can I say LOL. I have told my doctors I will NOT take chemo and I will not for any reason as my husband,2 brothers, Dad, Mom, Grand Parents, nephew have all passed with cancer and I will not go through what they did. I took care of my husband till he passed and made sure he had the very best of treatments and I did research 7 days a week and anytime I could but I will not go through what he did, he was a lot stronger than I am. As far as my kids are concerned they have not been to my house in over a year and I sure do not want them here now.
@@stanleykim1924. I have 🥶Stage 4 non 🥶Small Cell Adenocarcinoma 🥶lung cancer 🥶I am on immuno therapy only edit shrunk. My question is please God answer please please answer because I’ve asked for seven whole months and no one will answer me. Can it shrink and then come back and is stage four dogs leg cancer is it curable and about how what’s the average people live with it and I would love for you to tell me the truth because I know that you love us and we have a right to know if you know about how long we have because we have children to think about we love your videos, we pray for your wonderful family and thank you for saving many lives. Thank you so much for all you do. We love you please write back. Thank you.🥶 oh and is that a high-grade type of cancer or medium grade or low grade cancer Owen has anybody ever been cured of stage four lung cancer? Oh I’m sorry to bother you.
@@stanleykim1924 I’m 🩷using 🩷immunotherapy 🩷only 🩷with non-small cell ADENOCARCINOMA CARCINOMA, LUNG CANCER, AND UPPER LEFT LOBE AND BOTH LOWER LOBES . IT SHRINK JUST IN THE UPPER LEFT LOBE BUT NO CHANGES IN BOTH OF THE LOWER LUNG LOBES. MY QUESTION IS RESPECTIVELY. HOW LONG DO I GET TO LIVE PLEASE PLEASE GOD ANSWER PLEASE ANSWER. PLEASE TELL ME THE TRUTH AND THANK YOU SO MUCH WE LOVE YOU VERY MUCH AND WE TRUST YOU.
After ICPi was discontinued for severe irAEs, can the ICPi be resumed after patient recovered? A recent article suggested ‘watchful waiting’ instead of resuming ICPi especially when patient had response because about 40% continued in remission and 23% developed oligometastasis which could be controlled with radiation therapy. www.sciencedirect.com/science/article/pii/S2666364322001655
Dear Doctor, My mum’s main tumor (adenocarcinoma 1,575 inches large) is located in her right lower lobe and suspicious lesions were detected in her left lung. To date, she has undergone two cycles of chemo (carboplatine and pemetrexed) combined with immunotherapy (ipilimumab and nivolumab), two cycles of immunotherapy alone and one session of radiosurgery for her four brain metastases. Her main tumor shrank to 1,181 inches. Her doctor suggested that she quickly undergoes a lobectomy of her right lower lobe in order to reduce her tumor load. According to the new treatment standards, does surgery represent an adequate and beneficial treatment, even for a person with stage IV lung cancer, compared to radiotherapy? I thank you so much in advance for your precious reply.
In general, lobectomy to remove the primary tumor in stage IV adenocarcinoma is no a standard therapy unless all other metastatic tumors other than lung are complete eradicated. The brain metastasis may be under control with radio surgery, but it takes time to evaluate the accurate response. If the primary lung tumor has to be removed, stereotactic body radiotherapy may be less invasive than lobectomy. However, as I mentioned in the lecture, she must have biomarker tests with the tumor specimen for EGFR, ALK, ROS1, MET, RET, NTRK, KRASG12C, BRAF, or NRG1, etc. If any of the above turned out positive, targeted therapy should be given first. If all are negative, check for PD-L1 TPS number. But I am sure the treating oncologist did it all the above.
@@stanleykim1924 Dear Doctor, I thank you so much for your reply. My mother had a biomarker test which has not revealed the presence of any type of mutations. She is unfortunately not a candidate for targeted therapy. The level of PD-L1 in her tumor cells is inferior to 1%. Her four brain metastases have been successfully removed with radiosurgery but three new brain metastases have just appeared. Despite these data, we hope that lobectomy (if confirmed by pulmonary and cardiological tests) will be beneficial.
@@stanleykim1924 Dear Doctor, thank you very much for your reply. My mother had a biomarker test which did not reveal the presence of any type of mutation. Unfortunately, she is not a candidate for targeted therapy. The level of PD-L1 in his tumor cells is less than 1%. Here four brain metastases have been successfully removed by radiosurgery (Gamma Knife), but three new brain metastases have just appeared :( . Despite these results, we hope that a lobectomy (if confirmed by pulmonary and cardiological examinations) will be beneficial. My mother's oncologist is of the opinion that a surgery could allow further analysis of the tumor and lymph nodes, compared to body radiotherapy. All we have to do is pray that everything goes well.
Are you talking about EGFR exon 20 mutation? Mobocertinib - is a single molecule that binds to the EGFR protein within Exon 20 cancer cells and blocks growth signaling within the cell. Amivantamab - is a monoclonal anti-body that binds on the EGFR protein and blocks signaling to the protein in Exon 20 cells and calls in the body’s immune system for additional support.
FDA Approves New Therapies for Patients with NSCLC 1. Repotrectinib for ROS1 mutation. For patients with locally advanced or metastatic ROS1-positive NSCLC, repotrectinib became the first FDA-approved therapy for ROS1-positive patients who have received a prior ROS1 TKI or are TKI naive. This decision was based on data from the TRIDENT-1 study, which evaluated repotrectinib in a cohort of TKI-naive patients who had received up to one prior line of platinum-based chemotherapy or immunotherapy (n = 71) and patients with prior exposure to a ROS1 TKI without chemotherapy (n = 56). The confirmed overall response rate (ORR) was 79% (95% CI, 68-88) for TKI-naive patients and 38% (95% CI, 25-52) for patients with prior TKI exposure. The median durations of response were 34.1 months (95% CI, 25.6-not estimable) and 14.8 months (95% CI, 7.6-not estimable), respectively. Researchers noted that patients with measurable central nervous system metastases and resistance mutations after TKI therapy achieved responses. The FDA approved repotrectinib at a recommended daily dose of 160 mg orally for the first 14 days of treatment, increasing to 160 mg twice-daily until disease progression or unacceptable toxicity. www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-repotrectinib-ros1-positive-non-small-cell-lung-cancer 2. Pembrolizumab as a neoadjuvant with platinum based chemotherapy and adjuvant therapy KEYNOTE-671 (NCT03425643), a multicenter, randomized, double-blind, placebo-controlled trial in 797 patients with previously untreated and resectable Stage II, IIIA, or IIIB (N2) NSCLC by AJCC 8th edition. Patients were randomized (1:1) to either pembrolizumab or placebo, with platinum-based chemotherapy, every 3 weeks for 4 cycles (neoadjuvant treatment) followed by either continued single-agent pembrolizumab or placebo, every 3 weeks for up to 13 cycles (adjuvant treatment). Chemotherapy details and surgical window are provided in the above drug label link. The major efficacy outcome measures were overall survival (OS) and investigator-assessed event-free survival (EFS). Median OS was not reached in the pembrolizumab arm (95% CI: not estimable [NE], NE) and 52.4 months for those receiving placebo (95% CI: 45.7, NE) (hazard ratio [HR] 0.72 [95% CI: 0.56, 0.93]; p-value=0.0103). Median EFS was not reached in the pembrolizumab arm (95% CI: 34.1 months, NE) and 17 months in the placebo arm (95% CI: 14.3, 22.0) (HR 0.58 [95% CI: 0.46, 0.72]; p-value=
Neoadjuvant immunochemotherapy with durvalumab x 4 cycles before surgery for NasCLC stages II-IIIB showed improved complete pathological response and disease free survival. This is similar to nivolumab study I described in the lecture above. But the cPR rate of 17% appears slightly lower than that of nivolumab. www.nejm.org/doi/full/10.1056/NEJMoa2304875
Sotorasib adverse effect, especially liver dysfunction Patients who received anti-PD-L1 therapies within 12 weeks of initiating sotorasib were significantly more likely to develop these adverse events (P < .001) and to discontinue treatment (P = .014). ascopubs.org/doi/10.1200/PO.23.00030
A new study confirms that patients who developed immune related adverse effects with ICP inhibitors had improved survivals by more than a year: jamanetwork.com/journals/jamanetworkopen/fullarticle/2814052?PDF&PDFlink&PDF&.2023.52302
Sotorasib ( Lumakras) may not receive the final FDA approval due to no overall survival benefit: October 2023: Reuters) - Advisers to the U.S. Food and Drug Administration on Thursday found that data from a late-stage trial of Amgen's Lumakras could not be relied on, raising questions about the agency's upcoming decision on whether to grant traditional approval of the drug for a type of advanced lung cancer. The drug was approved by the FDA in 2021 under an accelerated pathway, with confirmatory data a condition for gaining traditional approval. The main goal of the confirmatory study was progression-free survival (PFS), or how long before the disease begins to worsen, but the FDA questioned some methods used in conducting the trial. An FDA spokesperson said the agency cannot comment on its next steps but it intends to keep the drug available for patients for now. "It is under accelerated approval and there are multiple pathways available to us. We are not making this move to withdraw the drug from the market," said Harpreet Singh of the FDA oncology division. The FDA's expert advisers voted 10 to 2 that the main goal of the late-stage confirmatory study could not be relied upon to assess the benefits of the drug, although several panel members noted that the voting question was very narrowly framed. Much of the committee's discussion centered on concerns that trial investigators allowed too many patients to switch between the treatment and control arms of the study. Data from the confirmatory study showed that Lumakras reduced the risk of disease progression in patients with advanced lung cancer by 34% compared with chemotherapy. Lumakras showed no significant difference in overall survival - the gold standard for cancer drugs - but Amgen said the study was not designed to demonstrate a survival benefit. The panel's decision was in line with an assessment from FDA staff reviewers, who suggested earlier this week that the trial data may be biased and may not be sufficient to confirm the benefits of Lumakras. They flagged several issues with the trial, including the way the study was conducted and loss of follow-up data from patients who withdrew consent. Lumakras is approved to treat advanced lung cancer in patients with mutations of the KRAS gene whose disease has worsened after chemotherapy or other treatments. The FDA grants accelerated approval where there is an unmet need and data demonstrating a drug is likely to work. It requires confirmatory trials be conducted to prove safety and efficacy in order to receive traditional approval. Lumakras is an oral drug designed to target a mutated form of a gene known as KRAS that occurs in about 13% of non-small cell lung cancers (NSCLC), the most common type of lung cancer, and less frequently in some other solid tumors. The FDA, which generally follows the advice of its expert panels but is not bound to do so, is expected to make a decision on the traditional approval for Amgen's drug by Dec. 24.
Sotorasib is not very effective as I explained above. But it’s case by case. In your case, sotorasib must have been working because your doctor continued for 12 months. Although its response amc effectiveness are generally not high, it has been effective to you. So congratulations!
Immunotherapy May be discontinued after 2 years of therapy if disease is progression free. A retrospective study showed no difference in survival whether immunotherapy is continued or discontinued after 2 years. However it is not a prospective study. jamanetwork.com/journals/jamaoncology/fullarticle/2805798
Sotorasib, the KRAS G12C inhibitor May increase toxicity, especially hepatotoxicity, when used within 30 days of the last Immunotherapy with ICIs. www.sciencedirect.com/science/article/abs/pii/S1556086423005725
Please see the comments I made on 11/27/23: Hepatotoxicity is more common when ICI immunotherapy was used within 3 months before starting date of Sotorasib, not 30 days as below: Sotorasib adverse effect, especially liver dysfunction Patients who received anti-PD-L1 therapies within 12 weeks of initiating sotorasib were significantly more likely to develop these adverse events (P < .001) and to discontinue treatment (P = .014). ascopubs.org/doi/10.1200/PO.23.00030
Dear Dr.Stanley Kim, My mom was diagnosed with stage 4 metastatic non-small cell lung cancer NSCLC back in August 2020. Today, it's been 11 months since she started with Tagrisso. My question is, What's after Tagrisso? Is there any news on this matter? Any insights from you would be appreciated.
If your mother has been taking it for 11 months, it is a good sign because if it had not worked, it would have stopped already. I hope she continues respond.
![ช้างศึกสู้ต่อไป!! พาเปียโน ดูบอลไทยครั้งแรก ตกรอบแบบโคตรเสียดาย!! l [Nickynachat]](http://i.ytimg.com/vi/4WloIH645Lg/mqdefault.jpg)
This video has given me some hope ! My dad has just been told he has tours in his lung and liver ! I am praying they can do something for him. 😢🙏🏻
Tours?
I think it is a good news of a great development and fortune for the patients being suffered for a long time.
Thank you so much igho for your full dedication am very happy and proud to come across your TH-cam channel. Your medications is indeed incomparable, my four years cancer disappeared completely within 15 days of usage and without any side effects, keep saving lives doctor.
At 5:18, I mistakenly said combined squamous cell carcinoma-> should have said ‘Combined small cell carcinoma’
I have stage 4 nsclc. I was dx December 2019. Exactly 4 years ago. First 6 treatments Keytruda/carbo/alimta (spelling is bad lol). Then went to Keytruda/alimta til August 2021. Keytruda affected my adrenal gland and thyroid. But doing well. I have just ended alimta lady month due to neurological and other side effects. But, I am still here, working and figuring out my new normal. Just did the blood work for Signatera and waiting results. My scans show only scaring now. Mets to adrenal gland is stable, Mets lymph nodes all around neck and obstruction to trechea and chest , ned😁. Thanks for your video! Very interesting. I am very curious to what the new stats show for survival. I believe it will show a huge difference.
Congratulations, and wish you the best!
Very informative video for the latest development of this field!
You are amazing. Thank you Sir for this clarity.
Dr. Kim, thank you very much for the lecture, how can we obtain your slides?
@stanleykim can you please make a lecture on TKi, PARP Inhibitors.
thank you
What about THIO-101?
Targeting Telomeres to Clear Cancer -
Short vs Long Telomerase | Aubrey De Grey
Hello , My Father has Stage 4 a lung cancer with local lung metastasis. Currently have started carboplatin and pemetrexed. Awaiting results pf Genome reports . But he is very healthy and active even after one cycle of chemo , (touch wood) but I am very much terrified. Please pray for him and give me some hope to stay positive as he is my only reason for my survival 😭
With new treatments, your father will have much better prognosis.
Thank you so much
It is positive for egfr and currently treated with geftinib and chemotherapy. Hoping for a miracle . Please bless us
For EGFR (+) non small cell lung cancer, anti-EGFR TKI drugs such as gefitinib (but osimertinib is more preferred) are used alone without chemotherapy. But some studies showed combination of anti-EGFR TKI and chemotherapy may be effective.
Good luck and God bless the patient!
Thanks a ton …… Is there any chance of surgery for stage 4 cancer spread only to right lung ? Like atleast surgery or radiation ????
Thank you 🙏
You’re welcome!
In October of 2023I was diagnosed with nsc stage 4 lung cancer which spread to the brain. I was in the hospital for three weeks and had ten rounds on brain radiation. In December i started chemo and immunotherapy. I just finished my sixth treatment last week. I'm taking Keytruda, Alimta and Carboplatin. I went for a MRI and CT scan in February and the oncologist had good news for me. Everything is shrinking and there is no new growth and nothing is spreading. Now I'm taking Keytruda and Alimta for the next 12 months after that it will just be Keytruda for the next 12 months after that. I've had no major side effects other than slight change in taste and slight appetite change. I'm still eating but not the same foods as before. I'm hoping for continued success with this treatment. The nodule they originally found on my right lung in October was 1.5cm.
I hope your treatments continue to work. You are very brave to fight so hard. I have stage 3B large cell neuroendocrine lung cancer and have finished all possible chemo and rads to try to stop it.. Hoping very hard for slow spread.... (good response but not remission of course with this cancer).
Very best to you in your fight. I think there are many of us together in this.
Victor. Your story is similar to mine. I am taking Zepzelca chemo once a month at the lowest dose. I’m only taking it as a precaution for no reoccurrence even though I could quit all together as I’m cancer free . You won’t believe me .. but my cancer went dormant as soon as I started taking Fenbendezol. It’s a dog dewormer. Crazy I know. But I was given 6 months and I’m here 3 years later. Joe Tippens Protocol. If treatment fails for you.. look it up. Good luck!
Dear doctor, what's the tratament for Nsclc stage 4 egfr + exxon 19 del after progression on Tagrisso?
The US Food and Drug Administration has granted accelerated approval to tarlatamab-dlle (Imdelltra, Amgen) for extensive-stage small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy.
Tarlatamab is a first-in-class bispecific T-cell engager (BiTE) that binds delta-like ligand 3 on the surface of cells, including tumor cells, and CD3 expressed on the surface of T-cells. It causes T-cell activation, release of inflammatory cytokines, and lysis of DLL3-expressing cells, according to labeling.
Approval was based on data from 99 patients in DeLLphi-301 trial with relapsed/refractory extensive-stage SCLC who had progressed after platinum-based chemotherapy Patients with symptomatic brain metastases, interstitial lung disease, noninfectious pneumonitis, and active immunodeficiency were excluded.
The overall response rate was 40%, and median duration of response 9.7 months. The overall response rate was 52% in 27 patients with platinum-resistant SCLC and 31% in 42 with platinum-sensitive disease.
Continued approval may depend on verification of clinical benefit in a confirmatory trial.
Labeling includes a box warning of serious or life-threatening cytokine release syndrome and neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome.
The most common adverse events, occurring in 20% or more of patients, were cytokine release syndrome, fatigue, pyrexia, dysgeusia, decreased appetite, musculoskeletal pain, constipation, anemia, and nausea.
The most common grade 3 or 4 laboratory abnormalities included decreased lymphocytes, decreased sodium, increased uric acid, decreased total neutrophils, decreased hemoglobin, increased activated partial thromboplastin time, and decreased potassium.
The starting dose is 1 mg given intravenously over 1 hour on the first day of the first cycle followed by 10 mg on day 8 and day 15 of the first cycle, then every 2 weeks until disease progression or unacceptable toxicity.
New bispecific T cell Engager (BiTE) for SCLC
In May 2024, the FDA has granted accelerated approval to tarlatamab-dlle (Imdelltra, Amgen) for extensive-stage small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy.
Tarlatamab is a first-in-class bispecific T-cell engager (BiTE) that binds delta-like ligand 3 on the surface of cells, including tumor cells, and CD3 expressed on the surface of T-cells. It causes T-cell activation, release of inflammatory cytokines, and lysis of DLL3-expressing cells.
Approval was based on data from 99 patients in DeLLphi-301 trial with relapsed/refractory extensive-stage SCLC who had progressed after platinum-based chemotherapy Patients with symptomatic brain metastases, interstitial lung disease, noninfectious pneumonitis, and active immunodeficiency were excluded.
The overall response rate was 40%, and median duration of response 9.7 months. The overall response rate was 52% in 27 patients with platinum-resistant SCLC and 31% in 42 with platinum-sensitive disease.
Continued approval may depend on verification of clinical benefit in a confirmatory trial.
Labeling includes a box warning of serious or life-threatening cytokine release syndrome and neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome.
The most common adverse events, occurring in 20% or more of patients, were cytokine release syndrome, fatigue, pyrexia, dysgeusia, decreased appetite, musculoskeletal pain, constipation, anemia, and nausea.
The most common grade 3 or 4 laboratory abnormalities included decreased lymphocytes, decreased sodium, increased uric acid, decreased total neutrophils, decreased hemoglobin, increased activated partial thromboplastin time, and decreased potassium.
The starting dose is 1 mg given intravenously over 1 hour on the first day of the first cycle followed by 10 mg on day 8 and day 15 of the first cycle, then every 2 weeks until disease progression or unacceptable toxicity.
EGFR 20 mutated NSCLC can be treated with afatinib.
Recent FDA approval of 2 other drugs include:
Mobocertinib - is a single molecule that binds to the EGFR protein within Exon 20 cancer cells and blocks growth signaling within the cell.
Amivantamab - is a monoclonal anti-body that binds on the EGFR protein and blocks signaling to the protein in Exon 20 cells and calls in the body’s immune system for additional support.
Mobocertinib was withdrawn from the market as of October 2023 as it did not fulfill the goal as a mono therapy for EGFR axon 20 insertion mutation: no benefit in overall survival.
Thanks for reaching for help I from Cape town South Africa my husband died November 2023 he was diagnosed with COVID pneumonia reading his biopsy results he had lung cancer he was diagnosed by pulmonigist at a private hospital he smoke and his parents died of lung cancer his Dr refuse to show me his full blood count results and diff count results I am a medical results officer 28 years don't know treatment but can read results I would like to to get closer for our children he lived on oxygen private hospital and Dr's don't know how hard it is family I expect it but not the children how many private hospital and Dr's pulmonigist take a a oath for granted bless you
New NCCN guidelines were added for NSCLC 2023
But these are already discussed in my presentation. In fact, these NCCN guidelines have been approved by FDA before. So it seems that the NCCN is following the FDA not preceding. Nevertheless the new NCCN guidelines have a few important points which were explained in detail.
1. Neoadjuvant immunochemothetapy: For the 2023 update (Version 1.2023), the NCCN panel added a recommendation that patients should be evaluated for perioperative (neoadjuvant or adjuvant) therapy before surgery. The panel recommends nivolumab + platinum-doublet chemotherapy as a neoadjuvant systemic therapy option for eligible patients with resectable (tumors ≥4 cm or node-positive) NSCLC based on clinical trial data and the FDA approval (see NSCL-E 1 of 3, page 349).20-22 For the 2023 update (Version 1.2023), the panel added a recommendation that all patients should be evaluated for neoadjuvant therapy, with strong consideration for patients with node-positive disease or tumors ≥4 cm and who have no contraindications for ICIs. Neoadjuvant therapy should not be used to attempt to induce resectability in patients who do not already meet criteria for resectability on initial evaluation.
2. Adjuvant targeted therapy: The NCCN panel recommends osimertinib as an adjuvant therapy option for eligible patients with completely resected (R0) stage IB (only T = 4 cm) to IIIA and stage IIIB (only T3N2)***EGFR mutation-positive ****NSCLC who have previously received adjuvant chemotherapy or are ineligible to receive platinum-based chemotherapy based on clinical trial data and the FDA approval.
3. Adjuvant immunotherapy after complete surgical resection: (1) Atezolizumab: The panel recommends atezolizumab as an adjuvant therapy option for eligible patients with PD-L1 levels ≥1% and completely resected stage IIB-IIIA, stage IIIB (only T3N2)***, or high-risk stage*IIA NSCLC who have previously received adjuvant chemotherapy based on clinical trial data and the FDA approval
(1) Pembrolizumab** For the 2023 update (Version 2.2023), the panel added a recommendation for adjuvant pembrolizumab for eligible patients with completely resected (R0) stage IIB-IIIA, stage IIIB (only T3N2)***, or high-risk*stage IIA NSCLC who are negative for EGFR exon 19 deletions, EGFR exon 21 L858R mutations, or ALK fusions****and who have previously received adjuvant chemotherapy based on clinical trial data and the FDA approval. * High-risk factors may include poorly differentiated tumors, vascular invasion, wedge resection, visceral pleural involvement, and unknown lymph node status (Nx).
**The panel added a caveat**that the benefit of adjuvant pembrolizumab is unclear for patients with PD-L1 levels
Thank you for the updates, Dr Kim. Happy New Year!
Your yellow highlighting during the lecture to tracks from your presentation because it's not clear if you can find out some way to highlight and yellow where it's clear where you can still read through the Highlight then it might be beneficial
Durvalumab (Imfinzi) administered sequentially as an adjuvant immunotherapy after platinum-based concurrent chemo radiation therapy (CRT) is already an established standard of care for the treatment of that type of lung cancer.
But the so-called "PACIFIC-2 Phase 3" trial for durvalumab concurrently administered with CRT aimed to address patients who progress or discontinue treatment during CRT did not achieve statistical significance for progression-free survival versus CRT alone. The drug company (AstroZeneca) also said that there was an increased rate of infection during the concurrent treatment period in the experimental arm.
In August 2023, NCCN issued new guidelines regarding adjuvant therapy (immuno and targeted) for NSCLC.
I must tell you that these recommendations have been presented in this TH-cam lecture already!
The National Comprehensive Cancer Network (NCCN) issued new guidelines for the treatment and management of patients with non-small cell lung cancer. Published in the Journal of the National Comprehensive Cancer Network, the document concentrates on treatment options for patients with resectable disease in the neoadjuvant and adjuvant settings.
In recent years, multiple new treatment options have become available for patients with NSCLC, corresponding to improvements in survival. The NCCN annually updates its guidelines for treatment to reflect advances in the field. The NCCN convened a panel of lung cancer experts to evaluate clinical data and offer up-to-date recommendations based on the best available evidence.
In the neoadjuvant setting, the expert panel recommended that systemic therapy may be offered following surgical evaluation to patients who are likely to receive perioperative chemotherapy. Based on data from the CheckMate 816 study, they recommended treatment with nivolumab and platinum-doublet chemotherapy for patients with resectable NSCLC and no PD-L/PD-L1 contraindications.
All patients should be evaluated to determine whether neoadjuvant therapy is an appropriate choice, according to the authors, although neoadjuvant therapy should not be used to prompt resectability in patients with unresectable tumors. Patients with node-positive disease and tumors 4 cm or greater in size should especially be considered for neoadjuvant therapy.
Because treatment with immune checkpoint inhibitors carries the risk for severe immune-mediated adverse events, health care providers should be trained to recognize the onset of these conditions. Patients should discontinue nivolumab at the onset of severe or life-threatening pneumonitis.
Based on data from the phase 3 ADAURA study, the experts recommended osimertinib as adjuvant systemic therapy for patients with complete resected stage IB-IIIA and stage IIIB (T3N2 only) EGFR-positive NSCLC who have received previous adjuvant chemotherapy or are ineligible for platinum-based chemotherapy.
“Although it is technically easier to use a resected specimen for molecular testing, it is also acceptable to use initial diagnostic biopsy specimens,” the authors wrote. “However, plasma cell-free/circulating tumor DNA testing is not recommended in this setting, because tissue is available and it is difficult to detect mutations in peripheral blood in patients with early-stage disease. The NCCN Guidelines include a caveat that if patients have oncogenic driver mutations and high PD-L1 levels, they should receive appropriate targeted therapy, such as osimertinib, and not immune checkpoint inhibitors and not both.”
Regarding immunotherapy, the panel endorsed atezolizumab as adjuvant therapy for patients with PD-L1 expression of 1% or greater and completely resected stage IIB-IIIA disease; completely resected stage IIIB disease (T3N2 only); or high-risk stage IIA disease with no EGFR exon 19 deletions, or exon 21 L858R mutations, or ALK fusions.
For eligible patients with the same characteristics, the panel also recommended adjuvant pembrolizumab, based on data from the PEARLS/KEYNOTE 091 clinical trial. The panelists defined high-risk characteristics as poorly differentiated tumors, vascular invasion, wedge resection, visceral pleural involvement, and unknown lymph node status. They cautioned that data from the trial left unclear the benefit of pembrolizumab in patients with a PD-L1 expression below 1%.
“Patients with ALK fusions, EGFR exon 19 deletions, or EGFR exon 21 L858R mutations have less benefit from immune checkpoint inhibitors,” the authors wrote. “Testing for PD-L1 status, EGFR mutations, and ALK fusions is recommended before administering atezolizumab or pembrolizumab as adjuvant therapy. For the 2023 update, the panel expanded the molecular testing criteria to include ALK fusions. Although it is technically easier to use a resected specimen for molecular testing, it is also acceptable to use initial diagnostic biopsy specimens.”
Neoadjuvant therapy with duevalumab and chemotherapy also showed improvement of event free survival. The pathological complete remission was also compatible with those with pembrolizumab (17%).
NEJM published the final result in November 2033. I have described it in this lecture.
www.nejm.org/doi/full/10.1056/NEJMoa2304875
New data showed that the bispecific antibody amivantamab (Rybrevant) combined with chemotherapy was better than chemotherapy alone in EGFR-mutated (axon 20 insertion) advanced non-small cell lung cancer (NSCLC).
www.nejm.org/doi/pdf/10.1056/NEJMoa2306441
patients with EGFR exon 20 insertion-mutated advanced NSCLC. These patients, who represent about 2% to 3% of NSCLC cases, have "historically poor" outcomes, with a 5-year overall survival rate of just 8%.
The FDA approved amivantamab in 2021 for EGFR exon 20 insertion-mutated advanced NSCLC after progression on platinum-based chemotherapy, but the PAPILLON trial explored whether combining the two therapies upfront would provide a more meaningful benefit.
In the trial, 308 treatment-naïve patients with locally advanced or metastatic NSCLC and documented exon 20 insertions were randomly assigned to amivantamab plus chemotherapy or chemotherapy alone. The median age was about 62 years, approximately half were female, and just over 60% were Asian - a similar patient profile as MARIPOSA and MARIPOSA-2.
It showed that amivantamab plus chemotherapy significantly increased progression-free survival (PFS). More specifically, after a median follow-up of 14.9 months, patients receiving the combination had a median PFS of 11.4 months vs 5.7 months with chemotherapy alone (hazard ratio [HR], 0.395; P < .0001). This benefit consistently occurred across predefined subgroups.
Amivantamab plus chemotherapy was associated with a lower risk of a second progression, with the median not reached vs 17.2 months with chemotherapy alone (HR, 0.493; P = .001).
A higher proportion of patients receiving the combination had an objective response -73% vs 47% - and these patients had a longer duration of response as well - 9.7 months vs 4.4 months.
The overall survival data were immature but showed a trend toward a reduced risk of death for those on the combination (HR, 0.675; P = .106).
The rates of grade ≥ 3 adverse events were 75% with amivantamab plus chemotherapy and 54% with chemotherapy alone, and adverse events leading to discontinuation of amivantamab occurred in 7% of patients. Pneumonitis/interstitial lung disease (ILD) was reported in 3% of patients in the combination therapy arm.
Thank you for this wonderful video. Would you be able to tell me if immunotherapy would be an option for a late stage cancer patient with an autoimmune disease (colitis)? If so what precautions would need to be taken and what symptoms would need to be looked out for?
Yes, you may. However, the side effects from the immunotherapy may be severe.
Please watch my lecture “immunotherapy side effects. “posted on TH-cam.
I wish you the best results and a quick recovery.
Will do, thank you
Hi, are there any targeted therapies in the pipeline for:
APC G1357*
EP300 EP300-EP300 deletion
ERRFI1 W34*
FUBP1 E169*
KEAP1 R413fs*45
MLL2 E856*
NOTCH2 N552fs*64
TP53 C277F
Dear Dr. Kim,
I have stage 3B large cell neuroendocrine lung cancer. I finished chemo (5 rounds etoposide and carboplatin) and 6 weeks of concurrent radiation. I had good response to this but of course not total remission. Now the only thing I am being offered next is Imfinzi. I did not have any PD-L1 expression found on my tumor sample. I am told that I do not have any mutations or markers found for targeted therapy or immunotherapy. Do you think that Imfinzi makes any sense for me? I am of course desperate to do something besides waiting for my cancer to grow back and spread to other areas of my body.
Thank you for your information here and any opinion you have for me.
I understand your question.
Usually immunotherapy is effective for PD-L1 positive tumors. However, not always. For instance, small cell lung cancer responds better with combination of Imfinzi and chemotherapy even in PD-L1 negative small cell cancer. Imfinzi is well tolerated drug (pneumonitis can be serious side effect), and is used in a clinical trial, so I would not reject your oncologist’s suggestion.
I sincerely hope your quick recovery.
@@stanleykim1924 Thank you so much for your reply. I do not want to risk the serious side effects if there is no hope of a response - but from all I have read it seems impossible to know. I still do not know what to do but I sincerely appreciate you taking the time to reply to me and I respect your answer.
God bless you.
New Guidelines by ACS for lung cancer screening issued in November 2023:
The new guidelines lowered the age for annual lung cancer screening among asymptomatic former or current smokers from 55-74 years to 50-80 years. The update also now considers a high-risk person anyone with a 20-pack-year history, down from a 30-pack-year history, and removes the requirement that former smokers must have quit within 15 years to be eligible for screening.
Hello, thank you for the extremely informative video. My husband has stsge 4 ALK postive. He has been taking steroids, and Alecensa for 6wks. Initially 2pills xtwice daily as he was so late to be diagnosed due to multiple false diagnosing then a very long waitfor pathology results. The oncologist thought he was too ill to cope with 3 pills as he was immobile due to extreme weight loss, agonising spinal pain, and low appetite. She had written him off. He has been on 3pills xtwice daily for 10days now with no side effects...so far. Hes becoming mobile again, albeit slow and with a stick. He is pain free due to pain relief patches and the steroids, and is gaining weight.
Am i correct in reading/hearing that you said this treatment is 80% successful? Does this mean successful cure?
Thank you
Gill
80% response rate, not cure.
But many patients who responded targeted therapy continue in remission many years.
Also check for PD-L1 score.
I wish him the best results and a long survival with you.
Does this involve fenbendozle and ivermectin? Many successful videos of people curing themselves!!!
I was diagnosed with Lung 🫁 cancer 06/23/23.
I’m @ peace with my diagnosis but my children are having a hard time dealing with it. 😢😢😢
You are very much loved by your children. Love can do many things: you will have encouragement and reason to fight cancer for cure or long survival.
May I ask what kind of cancer you have? I have grown married girls and grandkids, I have put off telling them, I think they know just by guessing. I had stage 1 non small cell but it has went to stage 2 or 3 will know for sure in a few days. I have always said I did not want to make it to 80 years of age and I truly do not, I know sounds weird what can I say LOL. I have told my doctors I will NOT take chemo and I will not for any reason as my husband,2 brothers, Dad, Mom, Grand Parents, nephew have all passed with cancer and I will not go through what they did. I took care of my husband till he passed and made sure he had the very best of treatments and I did research 7 days a week and anytime I could but I will not go through what he did, he was a lot stronger than I am. As far as my kids are concerned they have not been to my house in over a year and I sure do not want them here now.
@@stanleykim1924. I have 🥶Stage 4 non 🥶Small Cell Adenocarcinoma 🥶lung cancer 🥶I am on immuno therapy only edit shrunk. My question is please God answer please please answer because I’ve asked for seven whole months and no one will answer me. Can it shrink and then come back and is stage four dogs leg cancer is it curable and about how what’s the average people live with it and I would love for you to tell me the truth because I know that you love us and we have a right to know if you know about how long we have because we have children to think about we love your videos, we pray for your wonderful family and thank you for saving many lives. Thank you so much for all you do. We love you please write back. Thank you.🥶 oh and is that a high-grade type of cancer or medium grade or low grade cancer Owen has anybody ever been cured of stage four lung cancer? Oh I’m sorry to bother you.
@@stanleykim1924 I’m 🩷using 🩷immunotherapy 🩷only 🩷with non-small cell ADENOCARCINOMA CARCINOMA, LUNG CANCER, AND UPPER LEFT LOBE AND BOTH LOWER LOBES . IT SHRINK JUST IN THE UPPER LEFT LOBE BUT NO CHANGES IN BOTH OF THE LOWER LUNG LOBES. MY QUESTION IS RESPECTIVELY. HOW LONG DO I GET TO LIVE PLEASE PLEASE GOD ANSWER PLEASE ANSWER. PLEASE TELL ME THE TRUTH AND THANK YOU SO MUCH WE LOVE YOU VERY MUCH AND WE TRUST YOU.
Same here hard telling family 😢
Is NSCLC squamous cell HPV+ second primary tumor in both lungs and mediastinum curable ?
After ICPi was discontinued for severe irAEs, can the ICPi be resumed after patient recovered?
A recent article suggested ‘watchful waiting’ instead of resuming ICPi especially when patient had response because about 40% continued in remission and 23% developed oligometastasis which could be controlled with radiation therapy.
www.sciencedirect.com/science/article/pii/S2666364322001655
Dear Doctor,
My mum’s main tumor (adenocarcinoma 1,575 inches large) is located in her right lower lobe and suspicious lesions were detected in her left lung.
To date, she has undergone two cycles of chemo (carboplatine and pemetrexed) combined with immunotherapy (ipilimumab and nivolumab), two cycles of immunotherapy alone and one session of radiosurgery for her four brain metastases. Her main tumor shrank to 1,181 inches.
Her doctor suggested that she quickly undergoes a lobectomy of her right lower lobe in order to reduce her tumor load. According to the new treatment standards, does surgery represent an adequate and beneficial treatment, even for a person with stage IV lung cancer, compared to radiotherapy?
I thank you so much in advance for your precious reply.
In general, lobectomy to remove the primary tumor in stage IV adenocarcinoma is no a standard therapy unless all other metastatic tumors other than lung are complete eradicated.
The brain metastasis may be under control with radio surgery, but it takes time to evaluate the accurate response. If the primary lung tumor has to be removed, stereotactic body radiotherapy may be less invasive than lobectomy.
However, as I mentioned in the lecture, she must have biomarker tests with the tumor specimen for EGFR, ALK, ROS1, MET, RET, NTRK, KRASG12C, BRAF, or NRG1, etc.
If any of the above turned out positive, targeted therapy should be given first. If all are negative, check for PD-L1 TPS number. But I am sure the treating oncologist did it all the above.
@@stanleykim1924 Dear Doctor, I thank you so much for your reply. My mother had a biomarker test which has not revealed the presence of any type of mutations. She is unfortunately not a candidate for targeted therapy. The level of PD-L1 in her tumor cells is inferior to 1%. Her four brain metastases have been successfully removed with radiosurgery but three new brain metastases have just appeared. Despite these data, we hope that lobectomy (if confirmed by pulmonary and cardiological tests) will be beneficial.
@@stanleykim1924 Dear Doctor, thank you very much for your reply. My mother had a biomarker test which did not reveal the presence of any type of mutation. Unfortunately, she is not a candidate for targeted therapy. The level of PD-L1 in his tumor cells is less than 1%. Here four brain metastases have been successfully removed by radiosurgery (Gamma Knife), but three new brain metastases have just appeared :( . Despite these results, we hope that a lobectomy (if confirmed by pulmonary and cardiological examinations) will be beneficial. My mother's oncologist is of the opinion that a surgery could allow further analysis of the tumor and lymph nodes, compared to body radiotherapy. All we have to do is pray that everything goes well.
Hello sir
Any information about treatment of lung cancer with eGFR-19 mutation? Appreciate very much
Are you talking about EGFR exon 20 mutation?
Mobocertinib - is a single molecule that binds to the EGFR protein within Exon 20 cancer cells and blocks growth signaling within the cell.
Amivantamab - is a monoclonal anti-body that binds on the EGFR protein and blocks signaling to the protein in Exon 20 cells and calls in the body’s immune system for additional support.
But monocertinib was withdrawn from the market as it did not meet the goal: no overall survival benefit.
FDA Approves New Therapies for Patients with NSCLC
1. Repotrectinib for ROS1 mutation.
For patients with locally advanced or metastatic ROS1-positive NSCLC, repotrectinib became the first FDA-approved therapy for ROS1-positive patients who have received a prior ROS1 TKI or are TKI naive. This decision was based on data from the TRIDENT-1 study, which evaluated repotrectinib in a cohort of TKI-naive patients who had received up to one prior line of platinum-based chemotherapy or immunotherapy (n = 71) and patients with prior exposure to a ROS1 TKI without chemotherapy (n = 56).
The confirmed overall response rate (ORR) was 79% (95% CI, 68-88) for TKI-naive patients and 38% (95% CI, 25-52) for patients with prior TKI exposure. The median durations of response were 34.1 months (95% CI, 25.6-not estimable) and 14.8 months (95% CI, 7.6-not estimable), respectively.
Researchers noted that patients with measurable central nervous system metastases and resistance mutations after TKI therapy achieved responses. The FDA approved repotrectinib at a recommended daily dose of 160 mg orally for the first 14 days of treatment, increasing to 160 mg twice-daily until disease progression or unacceptable toxicity.
www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-repotrectinib-ros1-positive-non-small-cell-lung-cancer
2. Pembrolizumab as a neoadjuvant with platinum based chemotherapy and adjuvant therapy
KEYNOTE-671 (NCT03425643), a multicenter, randomized, double-blind, placebo-controlled trial in 797 patients with previously untreated and resectable Stage II, IIIA, or IIIB (N2) NSCLC by AJCC 8th edition. Patients were randomized (1:1) to either pembrolizumab or placebo, with platinum-based chemotherapy, every 3 weeks for 4 cycles (neoadjuvant treatment) followed by either continued single-agent pembrolizumab or placebo, every 3 weeks for up to 13 cycles (adjuvant treatment). Chemotherapy details and surgical window are provided in the above drug label link.
The major efficacy outcome measures were overall survival (OS) and investigator-assessed event-free survival (EFS). Median OS was not reached in the pembrolizumab arm (95% CI: not estimable [NE], NE) and 52.4 months for those receiving placebo (95% CI: 45.7, NE) (hazard ratio [HR] 0.72 [95% CI: 0.56, 0.93]; p-value=0.0103). Median EFS was not reached in the pembrolizumab arm (95% CI: 34.1 months, NE) and 17 months in the placebo arm (95% CI: 14.3, 22.0) (HR 0.58 [95% CI: 0.46, 0.72]; p-value=
Neoadjuvant immunochemotherapy with durvalumab x 4 cycles before surgery for NasCLC stages II-IIIB showed improved complete pathological response and disease free survival.
This is similar to nivolumab study I described in the lecture above. But the cPR rate of 17% appears slightly lower than that of nivolumab.
www.nejm.org/doi/full/10.1056/NEJMoa2304875
Sotorasib adverse effect, especially liver dysfunction
Patients who received anti-PD-L1 therapies within 12 weeks of initiating sotorasib were significantly more likely to develop these adverse events (P < .001) and to discontinue treatment (P = .014).
ascopubs.org/doi/10.1200/PO.23.00030
A new study confirms that patients who developed immune related adverse effects with ICP inhibitors had improved survivals by more than a year:
jamanetwork.com/journals/jamanetworkopen/fullarticle/2814052?PDF&PDFlink&PDF&.2023.52302
Sotorasib ( Lumakras) may not receive the final FDA approval due to no overall survival benefit:
October 2023:
Reuters) - Advisers to the U.S. Food and Drug Administration on Thursday found that data from a late-stage trial of Amgen's Lumakras could not be relied on, raising questions about the agency's upcoming decision on whether to grant traditional approval of the drug for a type of advanced lung cancer.
The drug was approved by the FDA in 2021 under an accelerated pathway, with confirmatory data a condition for gaining traditional approval.
The main goal of the confirmatory study was progression-free survival (PFS), or how long before the disease begins to worsen, but the FDA questioned some methods used in conducting the trial.
An FDA spokesperson said the agency cannot comment on its next steps but it intends to keep the drug available for patients for now.
"It is under accelerated approval and there are multiple pathways available to us. We are not making this move to withdraw the drug from the market," said Harpreet Singh of the FDA oncology division.
The FDA's expert advisers voted 10 to 2 that the main goal of the late-stage confirmatory study could not be relied upon to assess the benefits of the drug, although several panel members noted that the voting question was very narrowly framed.
Much of the committee's discussion centered on concerns that trial investigators allowed too many patients to switch between the treatment and control arms of the study.
Data from the confirmatory study showed that Lumakras reduced the risk of disease progression in patients with advanced lung cancer by 34% compared with chemotherapy.
Lumakras showed no significant difference in overall survival - the gold standard for cancer drugs - but Amgen said the study was not designed to demonstrate a survival benefit.
The panel's decision was in line with an assessment from FDA staff reviewers, who suggested earlier this week that the trial data may be biased and may not be sufficient to confirm the benefits of Lumakras.
They flagged several issues with the trial, including the way the study was conducted and loss of follow-up data from patients who withdrew consent.
Lumakras is approved to treat advanced lung cancer in patients with mutations of the KRAS gene whose disease has worsened after chemotherapy or other treatments.
The FDA grants accelerated approval where there is an unmet need and data demonstrating a drug is likely to work. It requires confirmatory trials be conducted to prove safety and efficacy in order to receive traditional approval.
Lumakras is an oral drug designed to target a mutated form of a gene known as KRAS that occurs in about 13% of non-small cell lung cancers (NSCLC), the most common type of lung cancer, and less frequently in some other solid tumors.
The FDA, which generally follows the advice of its expert panels but is not bound to do so, is expected to make a decision on the traditional approval for Amgen's drug by Dec. 24.
Could you please explain? I am in the UK and have been taking Sotorasib for 12 months.
Sotorasib is not very effective as I explained above. But it’s case by case. In your case, sotorasib must have been working because your doctor continued for 12 months.
Although its response amc effectiveness are generally not high, it has been effective to you. So congratulations!
Immunotherapy May be discontinued after 2 years of therapy if disease is progression free. A retrospective study showed no difference in survival whether immunotherapy is continued or discontinued after 2 years.
However it is not a prospective study.
jamanetwork.com/journals/jamaoncology/fullarticle/2805798
Sotorasib, the KRAS G12C inhibitor May increase toxicity, especially hepatotoxicity, when used within 30 days of the last Immunotherapy with ICIs.
www.sciencedirect.com/science/article/abs/pii/S1556086423005725
Please see the comments I made on 11/27/23:
Hepatotoxicity is more common when ICI immunotherapy was used within 3 months before starting date of Sotorasib, not 30 days as below:
Sotorasib adverse effect, especially liver dysfunction
Patients who received anti-PD-L1 therapies within 12 weeks of initiating sotorasib were significantly more likely to develop these adverse events (P < .001) and to discontinue treatment (P = .014).
ascopubs.org/doi/10.1200/PO.23.00030
Dear Dr.Stanley Kim,
My mom was diagnosed with stage 4 metastatic non-small cell lung cancer NSCLC back in August 2020. Today, it's been 11 months since she started with Tagrisso.
My question is, What's after Tagrisso? Is there any news on this matter? Any insights from you would be appreciated.
If your mother has been taking it for 11 months, it is a good sign because if it had not worked, it would have stopped already.
I hope she continues respond.
@@stanleykim1924 Thank you 🙏