Thank you so much for this information that is very helpful. Today, January 27, 2023, was my first time meeting you during my appointment. I sincerely hope you will be able to help me with my prostate issue. Thanks again.
Thanks so much for these lectures, Dr. Kim! As a PA-C who is new to the specialty of oncology, these are so helpful in getting acclimated to my new specialty! Your work on these lectures and your willingness to share your expertise are deeply appreciated!
Hi Dr Kim This was a wonderful and very informative presentation. I wish I could print a copy of all this ,like in PDf format to read. As one can not remember by just watching video. Is there a way get a print copy . thanks
On March 23, 2022, the Food and Drug Administration approved Pluvicto (lutetium Lu 177 vipivotide tetraxetan, Advanced Accelerator Applications USA, Inc., a Novartis company) for the treatment of adult patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor (AR) pathway inhibition and taxane-based chemotherapy. On the same day, the FDA approved Locametz (gallium Ga 68 gozetotide), a radioactive diagnostic agent for positron emission tomography (PET) of PSMA-positive lesions, including selection of patients with metastatic prostate cancer for whom lutetium Lu 177 vipivotide tetraxetan PSMA-directed therapy is indicated. Locametz is the first radioactive diagnostic agent approved for patient selection in the use of a radioligand therapeutic agent. Patients with previously treated mCRPC should be selected for treatment with Pluvicto using Locametz or another approved PSMA-11 imaging agent based on PSMA expression in tumors. PSMA-positive mCRPC was defined as having at least one tumor lesion with gallium Ga 68 gozetotide uptake greater than normal liver. Patients were excluded from enrollment if any lesions exceeding certain size criteria in the short axis had uptake less than or equal to uptake in normal liver (See full prescribing information, section 14). Efficacy was evaluated in VISION (NCT03511664), a randomized (2:1), multicenter, open-label trial that evaluated Pluvicto plus best standard of care (BSoC) (n=551) or BSoC alone (n=280) in men with progressive, PSMA-positive mCRPC. All patients received a GnRH analog or had prior bilateral orchiectomy. Patients were required to have received at least one AR pathway inhibitor, and 1 or 2 prior taxane-based chemotherapy regimens. Patients received Pluvicto 7.4 GBq (200 mCi) every 6 weeks for up to a total of 6 doses plus BSoC or BSoC alone. The trial demonstrated a statistically significant improvement in the primary endpoints of overall survival (OS) and radiographic progression-free survival (rPFS). Hazard ratio (HR) for OS was 0.62 (95% CI: 0.52, 0.74; p
With just five fractions of stereotactic body radiation therapy (SBRT), men with low- or intermediate-risk prostate cancer can have 5-year disease control as good as that provided by conventional external-beam radiation therapy delivered at higher doses in 20-39 fractions, according to new data from the phase 3 randomized PACE-B trial. Overall, the 5-year event-free survival rates were 95.8% among patients who received SBRT and 94.6% among those who had conventional radiation. The incidence of adverse events was also low in both groups, with no significant differences observed between the trial arms. The similar event-free survival and toxicity profiles in both groups provide more support for SBRT, which treats prostate cancer with larger radiation fractions over a shorter time period.
A large study from U.K. showed that 15- yr- survival rates of prostate cancer diagnosed by PSA screening at 15-yr were not different among active surveillance without treatment, surgery and radiation therapy group regardless of the baseline PSA level, grade, stage or risk stratification scores. Does it mean that early therapy may not be necessary even for high risk patients? www.nejm.org/doi/full/10.1056/NEJMoa2214122
Under your chart HORMONE THERAPY - ANTIANDROGENS You have an error You list Abiraterone as Zytiga ..and.. Apaludamide as Zytiga These are not the same drugs, and Apaludamide IS NOT ZYTIGA, it is ERLEADA Please correct this error as it is dangerously misleading
Docetaxel (Taxol) is used for castration resistant metastatic prostate cancer.And FDA approved cabazitxe for docetaxel-resistant or intolerable patients as the original study was designed that way. However, in my clinical practice, I preferred cabazitxel over docetaxel because of less fatigue, less hair loss, and less body aches. And often insurance companies approved cabazitxel. Now, a recent study (European Urology Mar. 2022) confirmed that Patients have better quality of life with cabazitxel over docetaxel (Taxol). www.sciencedirect.com/science/article/abs/pii/S0302283821021175?via%3Dihub
The US Food and Drug Administration (FDA) has added a boxed warning to the label of the osteoporosis drug denosumab (Prolia) about increased risk for severe hypocalcemia in patients with advanced chronic kidney disease (CKD). Denosumab is a monoclonal antibody, indicated for the treatment of postmenopausal women with osteoporosis who are at increased risk for fracture for whom other treatments aren't effective or can't be tolerated. It's also indicated to increase bone mass in men with osteoporosis at high risk for fracture, treat glucocorticoid-induced osteoporosis in men and women at high risk for fracture, increase bone mass in men at high risk for fracture receiving androgen-deprivation therapy for nonmetastatic prostate cancer, and increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer. This new warning updates a November 2022 alert based on preliminary evidence for a "substantial risk" for hypocalcemia in patients with CKD on dialysis.
Stampede platform protocol for non-metastatic high risk prostate cancer: Published in Lancet Dec.2021 As I mentioned, patients with non-metastatic high risk prostate cancer are treated with radiation therapy (often including regional LNs) concurrently with ADT. ADT continues for 3 years. Now the randomized study confirmed combining abiraterine 100mg/d and prednisone 5 mg/d for 2 years to 3 years of ADT improves metastasis-free survival at 6 years (median not reached with combined hormone Tx vs. 86 months with ADT alone). However the median overall survival rates in both groups did not reach by 6 years. Adding enzalutamide to aboraterone did not benefit when compared with aboraterone. www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02437-5/fulltext
The US Food and Drug Administration (FDA) has approved niraparib and abiraterone acetate (Akeega, Janssen Pharmaceuticals) to treat BRCA-positive, metastatic castration-resistant prostate cancer in adult patients with deleterious or suspected deleterious disease, as determined by an FDA-approved test. The FDA's approval was based on findings from the phase 3 MAGNITUDE precision medicine study, a randomized, placebo-controlled trial with 423 patients, 225 (53%) of whom had BRCA gene mutations as determined using a tissue assay such as FoundationOne CDx. Among the subgroup with a BRCA mutation, radiographic progression-free survival was a median of 16.6 months vs 10.9 months (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.36 - 0.79; P = .0014). In this subgroup, an exploratory overall survival analysis demonstrated a median of 30.4 months vs 28.6 months (HR, 0.79; 95% CI, 0.55 - 1.12), favoring the treatment arm. Although the overall cohort (those with and without BRCA mutations) demonstrated a significant improvement in radiographic progression-free survival, the subgroup with non-BRCA homologous recombination repair mutations did not demonstrate a significant improvement in radiographic progression-free survival, which indicates that the benefit observed was "primarily attributed" to the results in the subgroup of patients with BRCA mutations, according to the FDA.
Amazing study result: no difference in mortality rate between no treatment vs surgery vs radiation therapy for early prostate cancer. - NEJM March 2023 Fifteen-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer March 11, 2023 DOI: 10.1056/NEJMoa2214122 Abstract BACKGROUND Between 1999 and 2009 in the United Kingdom, 82,429 men between 50 and 69 years of age received a prostate-specific antigen (PSA) test. Localized prostate cancer was diagnosed in 2664 men. Of these men, 1643 were enrolled in a trial to evaluate the effectiveness of treatments, with 545 randomly assigned to receive active monitoring, 553 to undergo prostatectomy, and 545 to undergo radiotherapy. METHODS At a median follow-up of 15 years (range, 11 to 21), we compared the results in this population with respect to death from prostate cancer (the primary outcome) and death from any cause, metastases, disease progression, and initiation of long-term androgen-deprivation therapy (secondary outcomes). RESULTS Follow-up was complete for 1610 patients (98%). A risk-stratification analysis showed that more than one third of the men had intermediate or high-risk disease at diagnosis. Death from prostate cancer occurred in 45 men (2.7%): 17 (3.1%) in the active-monitoring group, 12 (2.2%) in the prostatectomy group, and 16 (2.9%) in the radiotherapy group (P=0.53 for the overall comparison). Death from any cause occurred in 356 men (21.7%), with similar numbers in all three groups. Metastases developed in 51 men (9.4%) in the active-monitoring group, in 26 (4.7%) in the prostatectomy group, and in 27 (5.0%) in the radiotherapy group. Long-term androgen-deprivation therapy was initiated in 69 men (12.7%), 40 (7.2%), and 42 (7.7%), respectively; clinical progression occurred in 141 men (25.9%), 58 (10.5%), and 60 (11.0%), respectively. In the active-monitoring group, 133 men (24.4%) were alive without any prostate cancer treatment at the end of follow-up. No differential effects on cancer-specific mortality were noted in relation to the baseline PSA level, tumor stage or grade, or risk-stratification score. No treatment complications were reported after the 10-year analysis. CONCLUSIONS After 15 years of follow-up, prostate cancer-specific mortality was low regardless of the treatment assigned. Thus, the choice of therapy involves weighing trade-offs between benefits and harms associated with treatments for localized prostate cancer.
Docitsxil or carbaxitaxil are the chemo drugs used for harmone resistant prostate cancer or in combination with ADT in high grade or high tumor burden cancer ( high risk).
Bone modifying agent, eg, denosumab (Xgeva) or zoledronc acid (Zometa) is not recommended for castration sensitive metastatic prostate cancer. It simply increases toxicity and raises health care expense without benefits. But it is recommended for castration resistant metastatic prostate cancer. ascopubs.org/doi/10.1200/OP.23.00602
For new metastatic prostate cancer, adding darolutamide to docetaxel and ADT improved survival. So FDA approved darolutamide in August 2022 for this occasion. www.nejm.org/doi/10.1056/NEJMoa2119115?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed. It caused seizure in 0.6% of patients participated. However, earlier study with enzalutamide in addition to docetaxel and ADT didn’t show benefits. Abiraterone helped just for patients with high risk high tumor burden only.
Hello doctor..my father had diagnosed locally advanced metastatic prostate cancer Gleason score 9, 4 months ago.his psa level was 46. The urologist treated him with TURP and bilateral orchiectomy.now his psa level is 0.29.. doctor prescribed for zoledronic acid injection for 6 moths and some calcium and vitamin d tablets and also Tabi 50 tablet.He is now fit and fine and joined his work place..what is the next step doctor? Please reply..Will he continue the Tabi 50 tablet??
The treatments your father received ate somewhat different from those being done in the US. Nevertheless, bilateral orchiectomy is a good choice in this circumstance. I would just follow up with periodic office visits and PSA. I wish the best results for your dad.
Thank you, Dr. Kim. My husband is going to have High intensity focused ultrasound (HIFU ) treatment in Second week of April. His 62 years old. His left lateral mid Adenocarcinoma, Gleason 3+3= 6 core involvement 5% (0.5mm) and lef Mid 3+3 =6 20% (2mm). My husband and I decided to do this procedure. Do you think we made the right decision for him? Or do you have any suggestions for us? I’m very worried for my husband. Please help us. Thank you!
I am sorry that your husband was diagnosed prostate cancer. However, it appears to be the best kind of prostate cancer: Very low risk Stage 1 prostate cancer. He can be treated with active surveillance or other eg, HIFU. Either way, he will have the best prognosis!
Abiraterone. or Zytiga is referred to as IRREVERSIBLE Does that mean that once a patient is given Abiraterone, his testosterone will never recover? Does that mean Abiraterone results in permanent CASTRATION??????
No, it means the drug binds the receptor irreversibly. But frequently cancer cells find other mechanism to grow. But surely Zytiga is a potent anti-testosterone.
Thank you so much for this information that is very helpful. Today, January 27, 2023, was my first time meeting you during my appointment. I sincerely hope you will be able to help me with my prostate issue. Thanks again.
Thanks so much for these lectures, Dr. Kim! As a PA-C who is new to the specialty of oncology, these are so helpful in getting acclimated to my new specialty! Your work on these lectures and your willingness to share your expertise are deeply appreciated!
Thank you and congratulations for your new endeavor!
At 10:04, Apalutamide (Zytiga) is an error: It should be Abiraterone (Zytiga).
i want zytiga please help me if you can
Hi Dr Kim This was a wonderful and very informative presentation. I wish I could print a copy of all this ,like in PDf format to read. As one can not remember by just watching video. Is there a way get a print copy .
thanks
I thank Dr Kim for this useful lecture.
You’re welcome!
On March 23, 2022, the Food and Drug Administration approved Pluvicto (lutetium Lu 177 vipivotide tetraxetan, Advanced Accelerator Applications USA, Inc., a Novartis company) for the treatment of adult patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor (AR) pathway inhibition and taxane-based chemotherapy.
On the same day, the FDA approved Locametz (gallium Ga 68 gozetotide), a radioactive diagnostic agent for positron emission tomography (PET) of PSMA-positive lesions, including selection of patients with metastatic prostate cancer for whom lutetium Lu 177 vipivotide tetraxetan PSMA-directed therapy is indicated. Locametz is the first radioactive diagnostic agent approved for patient selection in the use of a radioligand therapeutic agent.
Patients with previously treated mCRPC should be selected for treatment with Pluvicto using Locametz or another approved PSMA-11 imaging agent based on PSMA expression in tumors. PSMA-positive mCRPC was defined as having at least one tumor lesion with gallium Ga 68 gozetotide uptake greater than normal liver. Patients were excluded from enrollment if any lesions exceeding certain size criteria in the short axis had uptake less than or equal to uptake in normal liver (See full prescribing information, section 14).
Efficacy was evaluated in VISION (NCT03511664), a randomized (2:1), multicenter, open-label trial that evaluated Pluvicto plus best standard of care (BSoC) (n=551) or BSoC alone (n=280) in men with progressive, PSMA-positive mCRPC. All patients received a GnRH analog or had prior bilateral orchiectomy. Patients were required to have received at least one AR pathway inhibitor, and 1 or 2 prior taxane-based chemotherapy regimens. Patients received Pluvicto 7.4 GBq (200 mCi) every 6 weeks for up to a total of 6 doses plus BSoC or BSoC alone.
The trial demonstrated a statistically significant improvement in the primary endpoints of overall survival (OS) and radiographic progression-free survival (rPFS). Hazard ratio (HR) for OS was 0.62 (95% CI: 0.52, 0.74; p
With just five fractions of stereotactic body radiation therapy (SBRT), men with low- or intermediate-risk prostate cancer can have 5-year disease control as good as that provided by conventional external-beam radiation therapy delivered at higher doses in 20-39 fractions, according to new data from the phase 3 randomized PACE-B trial.
Overall, the 5-year event-free survival rates were 95.8% among patients who received SBRT and 94.6% among those who had conventional radiation. The incidence of adverse events was also low in both groups, with no significant differences observed between the trial arms.
The similar event-free survival and toxicity profiles in both groups provide more support for SBRT, which treats prostate cancer with larger radiation fractions over a shorter time period.
A large study from U.K. showed that 15- yr- survival rates of prostate cancer diagnosed by PSA screening at 15-yr were not different among active surveillance without treatment, surgery and radiation therapy group regardless of the baseline PSA level, grade, stage or risk stratification scores.
Does it mean that early therapy may not be necessary even for high risk patients?
www.nejm.org/doi/full/10.1056/NEJMoa2214122
Under your chart
HORMONE THERAPY -
ANTIANDROGENS
You have an error
You list Abiraterone as Zytiga ..and..
Apaludamide as Zytiga
These are not the same drugs, and Apaludamide IS NOT ZYTIGA, it is ERLEADA
Please correct this error as it is dangerously misleading
Docetaxel (Taxol) is used for castration resistant metastatic prostate cancer.And FDA approved cabazitxe for docetaxel-resistant or intolerable patients as the original study was designed that way.
However, in my clinical practice, I preferred cabazitxel over docetaxel because of less fatigue, less hair loss, and less body aches. And often insurance companies approved cabazitxel.
Now, a recent study (European Urology Mar. 2022) confirmed that Patients have better quality of life with cabazitxel over docetaxel (Taxol).
www.sciencedirect.com/science/article/abs/pii/S0302283821021175?via%3Dihub
thank you doctor kim.
The US Food and Drug Administration (FDA) has added a boxed warning to the label of the osteoporosis drug denosumab (Prolia) about increased risk for severe hypocalcemia in patients with advanced chronic kidney disease (CKD).
Denosumab is a monoclonal antibody, indicated for the treatment of postmenopausal women with osteoporosis who are at increased risk for fracture for whom other treatments aren't effective or can't be tolerated. It's also indicated to increase bone mass in men with osteoporosis at high risk for fracture, treat glucocorticoid-induced osteoporosis in men and women at high risk for fracture, increase bone mass in men at high risk for fracture receiving androgen-deprivation therapy for nonmetastatic prostate cancer, and increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer.
This new warning updates a November 2022 alert based on preliminary evidence for a "substantial risk" for hypocalcemia in patients with CKD on dialysis.
Stampede platform protocol for non-metastatic high risk prostate cancer: Published in Lancet Dec.2021
As I mentioned, patients with non-metastatic high risk prostate cancer are treated with radiation therapy (often including regional LNs) concurrently with ADT. ADT continues for 3 years.
Now the randomized study confirmed combining abiraterine 100mg/d and prednisone 5 mg/d for 2 years to 3 years of ADT improves metastasis-free survival at 6 years (median not reached with combined hormone Tx vs. 86 months with ADT alone). However the median overall survival rates in both groups did not reach by 6 years.
Adding enzalutamide to aboraterone did not benefit when compared with aboraterone.
www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02437-5/fulltext
The US Food and Drug Administration (FDA) has approved niraparib and abiraterone acetate (Akeega, Janssen Pharmaceuticals) to treat BRCA-positive, metastatic castration-resistant prostate cancer in adult patients with deleterious or suspected deleterious disease, as determined by an FDA-approved test.
The FDA's approval was based on findings from the phase 3 MAGNITUDE precision medicine study, a randomized, placebo-controlled trial with 423 patients, 225 (53%) of whom had BRCA gene mutations as determined using a tissue assay such as FoundationOne CDx.
Among the subgroup with a BRCA mutation, radiographic progression-free survival was a median of 16.6 months vs 10.9 months (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.36 - 0.79; P = .0014). In this subgroup, an exploratory overall survival analysis demonstrated a median of 30.4 months vs 28.6 months (HR, 0.79; 95% CI, 0.55 - 1.12), favoring the treatment arm.
Although the overall cohort (those with and without BRCA mutations) demonstrated a significant improvement in radiographic progression-free survival, the subgroup with non-BRCA homologous recombination repair mutations did not demonstrate a significant improvement in radiographic progression-free survival, which indicates that the benefit observed was "primarily attributed" to the results in the subgroup of patients with BRCA mutations, according to the FDA.
Amazing study result: no difference in mortality rate between no treatment vs surgery vs radiation therapy for early prostate cancer.
- NEJM March 2023
Fifteen-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer
March 11, 2023 DOI: 10.1056/NEJMoa2214122
Abstract
BACKGROUND
Between 1999 and 2009 in the United Kingdom, 82,429 men between 50 and 69 years of age received a prostate-specific antigen (PSA) test. Localized prostate cancer was diagnosed in 2664 men. Of these men, 1643 were enrolled in a trial to evaluate the effectiveness of treatments, with 545 randomly assigned to receive active monitoring, 553 to undergo prostatectomy, and 545 to undergo radiotherapy.
METHODS
At a median follow-up of 15 years (range, 11 to 21), we compared the results in this population with respect to death from prostate cancer (the primary outcome) and death from any cause, metastases, disease progression, and initiation of long-term androgen-deprivation therapy (secondary outcomes).
RESULTS
Follow-up was complete for 1610 patients (98%). A risk-stratification analysis showed that more than one third of the men had intermediate or high-risk disease at diagnosis. Death from prostate cancer occurred in 45 men (2.7%): 17 (3.1%) in the active-monitoring group, 12 (2.2%) in the prostatectomy group, and 16 (2.9%) in the radiotherapy group (P=0.53 for the overall comparison). Death from any cause occurred in 356 men (21.7%), with similar numbers in all three groups. Metastases developed in 51 men (9.4%) in the active-monitoring group, in 26 (4.7%) in the prostatectomy group, and in 27 (5.0%) in the radiotherapy group. Long-term androgen-deprivation therapy was initiated in 69 men (12.7%), 40 (7.2%), and 42 (7.7%), respectively; clinical progression occurred in 141 men (25.9%), 58 (10.5%), and 60 (11.0%), respectively. In the active-monitoring group, 133 men (24.4%) were alive without any prostate cancer treatment at the end of follow-up. No differential effects on cancer-specific mortality were noted in relation to the baseline PSA level, tumor stage or grade, or risk-stratification score. No treatment complications were reported after the 10-year analysis.
CONCLUSIONS
After 15 years of follow-up, prostate cancer-specific mortality was low regardless of the treatment assigned. Thus, the choice of therapy involves weighing trade-offs between benefits and harms associated with treatments for localized prostate cancer.
Docitsxil or carbaxitaxil are the chemo drugs used for harmone resistant prostate cancer or in combination with ADT in high grade or high tumor burden cancer ( high risk).
Bone modifying agent, eg, denosumab (Xgeva) or zoledronc acid (Zometa) is not recommended for castration sensitive metastatic prostate cancer. It simply increases toxicity and raises health care expense without benefits. But it is recommended for castration resistant metastatic prostate cancer.
ascopubs.org/doi/10.1200/OP.23.00602
Why didn’t you mention HIFU as a treatment? Or is this an infomercial…
It is used for early stage or as a salvage therapy
Excellent
For new metastatic prostate cancer, adding darolutamide to docetaxel and ADT improved survival.
So FDA approved darolutamide in August 2022 for this occasion.
www.nejm.org/doi/10.1056/NEJMoa2119115?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed.
It caused seizure in 0.6% of patients participated.
However, earlier study with enzalutamide in addition to docetaxel and ADT didn’t show benefits.
Abiraterone helped just for patients with high risk high tumor burden only.
Hello doctor..my father had diagnosed locally advanced metastatic prostate cancer Gleason score 9, 4 months ago.his psa level was 46. The urologist treated him with TURP and bilateral orchiectomy.now his psa level is 0.29.. doctor prescribed for zoledronic acid injection for 6 moths and some calcium and vitamin d tablets and also Tabi 50 tablet.He is now fit and fine and joined his work place..what is the next step doctor? Please reply..Will he continue the Tabi 50 tablet??
The treatments your father received ate somewhat different from those being done in the US.
Nevertheless, bilateral orchiectomy is a good choice in this circumstance. I would just follow up with periodic office visits and PSA. I wish the best results for your dad.
Thank you, Dr. Kim. My husband is going to have High intensity focused ultrasound (HIFU ) treatment in Second week of April. His 62 years old. His left lateral mid Adenocarcinoma, Gleason 3+3= 6 core involvement 5% (0.5mm) and lef Mid 3+3 =6 20% (2mm). My husband and I decided to do this procedure. Do you think we made the right decision for him? Or do you have any suggestions for us? I’m very worried for my husband. Please help us. Thank you!
I am sorry that your husband was diagnosed prostate cancer. However, it appears to be the best kind of prostate cancer: Very low risk Stage 1 prostate cancer.
He can be treated with active surveillance or other eg, HIFU.
Either way, he will have the best prognosis!
@@stanleykim1924 Thank you, Dr Kim! With HIFU treatment how likely is it that the cancer may return?
The reference study of lutatium 177 PSMA molecular therapy.
www.nejm.org/doi/full/10.1056/nejmoa2107322
Abiraterone. or Zytiga is referred to as IRREVERSIBLE
Does that mean that once a patient is given Abiraterone, his testosterone will never recover? Does that mean Abiraterone results in permanent CASTRATION??????
No, it means the drug binds the receptor irreversibly. But frequently cancer cells find other mechanism to grow. But surely Zytiga is a potent anti-testosterone.