Advertisement


Alan H. Bryce, MD, on Prostate Cancer: Phase III Results on Rucaparib, Docetaxel, and Androgen Pathway Inhibitor Therapy

2023 ASCO Genitourinary Cancers Symposium

Advertisement

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).



Transcript

Disclaimer: This video transcript has not been proofread or edited and may contain errors.
This is a Phase III registrational study which tested whether Rucaparib could improve radiographic progression-free survival in patients with BRCA1, BRCA2, or ATM-altered metastatic, castration-resistant prostate cancer. To be eligible for the study, the patient had to have a qualifying pathogenic alteration in one of those three genes, and they had to be previously treated with at least one androgen receptor pathway inhibitor. Importantly, docetaxel could not have been used in the castration resistance setting, so this is really a pre-docetaxel clinical trial for CRPC. But the patients could have received docetaxel in the hormone sensitive setting, which was given in just over 20% of patients. At GU ASCO23, we presented the final analysis of the primary endpoint of radiographic progression-free survival, which indeed showed that Rucaparib is superior to standard of care physician's choice therapy. Importantly, the physician's choice therapy in this study included docetaxel, abiraterone, and enzalutamide. So really it was meant to reflect real world practice where the treating physician had the liberty to choose whatever they felt was the best possible treatment for the patient. Rucaparib was superior to that panel of options with a 50% improvement in RPFS or death. So this was statistically significant with a median RPFS of 11 months versus six. And importantly in the subgroup analysis, Rucaparib was superior to docetaxel and to either abiraterone or enzalutamide. As it turned out, of the patients on the control arm, 55% were treated with docetaxel and we presented those results here at ASCO. This is the first time after 30 years of doing clinical trials, trying to beat docetaxel, that any agent has beaten a docetaxel containing control arm in an mCRPC study. It's the only PARP inhibitor to have done that. We really accomplished two main things here. One is the current label for rucaparib as in the post-docetaxel setting, so now we can comfortably say that rucaparib is appropriate in the pre-docetaxel setting, and we've demonstrated the superiority of rucaparib over docetaxel, which, as we saw in the study, is felt by most investigators to be the most appropriate alternative therapy for these patients. So the clinical implications are certainly that rucaparib monotherapy can be applied earlier in the disease course than the current approved indication. Of course, that's pending regulatory determination and review of the results. This becomes a very attractive option then for patients who have BRCA1 or 2 mutations and who have progressed after at least one ARPI. An important piece and data that we did discuss was the fact that the benefit is really in the BRCA subgroup and not in the ATM subgroup. That's not surprising data. It's consistent with prior clinical trials, but I do think in clinical application, it's something we want to emphasize. So for next steps, certainly the first question is going to be FDA acceptance of the results. Will they give an expanded label indication to move Rucaparib earlier? Of course, that's necessary before clinicians in the United States can use Rucaparib in an earlier line setting. We will look at secondary analyses then, right? We'll look at the quality of life data, we'll look at analyses by further subsets, and I think this will be important for the treating clinician, right, to optimize use of the drug.

Related Videos

Kidney Cancer

Michael B. Atkins, MD, on Renal Cell Carcinoma: Phase II Findings on Nivolumab and Ipilimumab

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).

Bladder Cancer

Andrea Necchi, MD, on Bladder Cancer: Phase II Results With Pembrolizumab Monotherapy

Andrea Necchi, MD, of Italy’s Vita-Salute San Raffaele University and the IRCCS San Raffaele Hospital and Scientific Institute, discusses new data from the KEYNOTE-057 trial on a novel systemic therapy for papillary high-risk non–muscle-invasive bladder cancer. The findings suggest that patients whose disease does not respond to bacillus Calmette-Guérin or who declined or were ineligible for a radical cystectomy may benefit from pembrolizumab monotherapy. (Abstract LBA442).

Kidney Cancer

Toni K. Choueiri, MD, on Renal Cell Carcinoma: Potential Predictive Biomarkers of Treatment Efficacy

Toni K. Choueiri, MD, of Dana-Farber Cancer Institute, discusses a biomarker analysis from the phase III CheckMate 9ER trial of nivolumab plus cabozantinib vs sunitinib for the treatment of patients with advanced renal cell carcinoma. The ongoing study aims to identify a predictive biomarker that may potentially guide therapeutic choices. (Abstract 608).

Bladder Cancer

Daniel P. Petrylak, MD, on Urothelial Cancer: Phase II Trial Analysis of Sacituzumab Govitecan-hziy in Metastatic Disease

Daniel P. Petrylak, MD, of the Yale Cancer Center, discusses a primary phase II analysis of the TROPHY-U-01 study, cohort 2, which evaluated sacituzumab govitecan-hziy in platinum-ineligible patients with metastatic urothelial cancer that progressed after prior checkpoint inhibitor therapy. (Abstract 520).

Prostate Cancer

Daniel P. Petrylak, MD, on Prostate Cancer: Latest Data on Pembrolizumab Plus Docetaxel

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).

Advertisement

Advertisement




Advertisement