Daniel P. Petrylak, MD, on Prostate Cancer: Latest Data on Pembrolizumab Plus Docetaxel
2023 ASCO Genitourinary Cancers Symposium
Daniel P. Petrylak, MD, of the Yale Cancer Center, discusses phase III findings from the KEYNOTE-921 study, which was designed to assess the combination of pembrolizumab and docetaxel in the treatment of patients with metastatic castration-resistant prostate cancer. They had not received chemotherapy, but their disease progressed on the next-generation hormonal agent, or they could not tolerate the agent. (Abstract 19).
Transcript
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
The keynote study in metastatic prostate cancer was designed to ask the question as to whether immune therapy improved the survival and their radiographic progression-free survival of patients treated with Docetaxel with castrate resistant prostate cancer. The median survival of patients with Docetaxel is generally about 19 months. However, other studies have demonstrated that when Docetaxel is administered after next generation anti-androgens, the survival is somewhat lower, about 13 months. So, in a phase two trial, it was determined that the median survival of Docetaxel combined with Pembrolizumab was approximately 19 months, and this was the impetus for going fourth with a phase three trial comparing Docetaxel plus Pembrolizumab to the standard of care Docetaxel. In both arms, prednisone was administered at five milligrams BID. Unfortunately, the results of the study demonstrated that there was no improvement in radiographic progression-free survival or overall survival. The implications of this are that, at least from this particular standpoint, immune checkpoint therapy does not change the standard of care for chemotherapy for metastatic castration resistant prostate cancer.
What we need to do is to move forward and look at the different molecular markers. We've collected tissue as part of this particular trial, it was a requirement to see those patients who've responded to Docetaxel if there is any molecular signature that we can use. We know that Pembrolizumab is FDA approved in those patients who have microsatellite instability with metastatic prostate cancer, but that only represents 2% of the population, and there have been responses observed with Pembrolizumab in those patients who do not have microsatellite instability. We have to understand, of course, what the proper signature is for that. So, the future trials will not be looking at simple checkpoint therapy combined with chemotherapy in this particular setting, but will focus on looking at molecular signatures that may improve the response rates to immune therapy and to chemotherapy, and potentially combine the two of them together.
The ASCO Post Staff
Michael B. Atkins, MD, of Georgetown Lombardi Comprehensive Cancer Center, discusses treatment-free survival outcomes from the HCRN GU16-260-Cohort A study of patients with previously untreated advanced clear cell renal cell carcinoma who received nivolumab and salvage nivolumab plus ipilimumab. The regimen appears to result in substantial treatment-free survival with few treatment-related adverse events. (Abstract 604).
The ASCO Post Staff
Matt D. Galsky, MD, of the Icahn School of Medicine at Mount Sinai and Tisch Cancer Institute, discusses final overall survival data from the phase III IMvigor130 study, which compared atezolizumab versus placebo, both of which were paired with platinum and gemcitabine in the first-line treatment of patients with locally advanced or metastatic urothelial carcinoma. (Abstract LBA440).
The ASCO Post Staff
Laurence Albiges, MD, PhD, of France’s Gustave Roussy Cancer Centre, discusses interim results from the CaboPoint study, which evaluated cabozantinib as second-line treatment in patients with unresectable, locally advanced or metastatic renal cell carcinoma with a clear cell component. Disease in the study participants had progressed after prior treatment with ipilimumab and nivolumab in combination or combined with VEGF-targeted therapy. (Abstract 606).
The ASCO Post Staff
Alan H. Bryce, MD, of the Mayo Clinic, discusses the final results of the primary endpoint of rPFS and interim results on overall survival among patients with chemotherapy-naive metastatic castration-resistant prostate cancer. The data showed that rucaparib improved radiographic progression-free survival compared with either docetaxel or abiraterone and enzalutamide in disease with BRCA1/2 alterations. (Abstract 18).
The ASCO Post Staff
Paul L. Nguyen, MD, of Dana-Farber Cancer Institute and Harvard Medical School, discusses results from the FORMULA-509 study, which compared postoperative salvage radiotherapy and 6 months of GnRH agonist with or without abiraterone acetate/prednisone (AAP) and apalutamide, after radical prostatectomy. The study suggested that adding AAP and apalutamide to salvage radiotherapy, plus 6 months of androgen-deprivation therapy, may improve outcomes, particularly in the subgroup of patients with a prostate-specific antigen level higher than 0.5 ng/mL. (Abstract 303).