Daniel P. Petrylak, MD, on Urothelial Cancer: Phase II Trial Analysis of Sacituzumab Govitecan-hziy in Metastatic Disease
2023 ASCO Genitourinary Cancers Symposium
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).
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
The treatment of metastatic urothelial carcinoma has evolved over the past 10 years and really has come a long way. Around 2010, if a patient had metastatic bladder cancer, there were two options for platinum eligible patients, those included the MVAC chemotherapy regimen as well as gemcitabine and cisplatinum. Carboplatinum and gemcitabine was considered a standard of care for those patients who were not eligible to receive cisplatin based chemotherapy. Unfortunately, once a patient progressed after any of these regimens, the median survival was about six months. With the use of checkpoint inhibition therapy, as well as the ADCs or the antibody drug conjugates that are showing significant activity in urothelial carcinoma, we've been able to treat patients that have been otherwise refractory to treatment. So we do need more treatments for the treatment of refractory urothelial carcinoma, as well as platinum ineligible urothelial carcinoma. And that was the point of the second group of the TROPHY study.
So we took patients who were ineligible to receive cisplatinum and treated those patients with Sacituzumab govitecan. We found that the response rate was 32% in all patients treated. Additionally, we found that in those patients who did not receive either prior chemotherapy or enfortumab vedotin, that the response rate was more than 50%. The toxicities that we observed with this study included neutropenia as well as diarrhea, and these were consistent with what was reported with the first cohort of the TROPHY study. So in summary, Sacituzumab govitecan has activity in platinum ineligible urothelial carcinoma, and further studies are being performed to look at the combination of Sacituzumab with checkpoint inhibition therapy. Additionally, there are studies that are ongoing with Sacituzumab combined with cisplatin in cisplatinum eligible patients. So this drug can form the core for the development of future therapies for refractory, as well as first line urothelial carcinoma.
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).
Scott T. Tagawa, MD, of Weill Cornell Medicine, NewYork-Presbyterian Hospital, discusses study results showing that, the anti-PSMA (prostate-specific membrane antigen) monoclonal antibody J591 with ketoconazole and hydrocortisone, when radiolabeled with lutetium-177, leads to improved 18-month metastasis-free survival vs radiolabeling with indium-111 in patients with nonmetastatic (M0) castration-resistant prostate cancer. This supports the development of anti-PSMA radioimmunotherapy, although the optimal radionuclide and targeting agent are unknown. (Abstract LBA21).
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).
Neeraj Agarwal, MD, of the Huntsman Cancer Institute, University of Utah, discusses phase III results from the TALAPRO-2 study, which suggested an improvement in radiographic progression-free survival with the combination of talazoparib and enzalutamide over standard-of-care enzalutamide alone as first-line treatment in patients with metastatic castration-resistant prostate cancer. The improvement was seen regardless of homologous recombination repair gene mutations. The combination regimen delayed the time to chemotherapy and worsening in global health status and quality of life. (Abstract LBA17).
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).