Laurence Albiges, MD, PhD, on Renal Cell Carcinoma: New Phase II Data on Cabozantinib and Checkpoint Inhibitor Therapy
2023 ASCO Genitourinary Cancers Symposium
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).
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
Standard of care for renal cell carcinoma is combination therapy, meaning in patients with clear cell RCC, we have access either to a combination of doublet IO, namely nivolumab plus ipilimumab, or a combination of VGF targeting plus an immune checkpoint, such as axitinib, pembrolizumab, cabozantinib, nivolumab, or lenvatinib, pembrolizumab as well. Right now, what we don't know is what we should do in patient who failed first line therapy, meaning having disease progression under first line therapy. The purpose of CaboPoint study that has been presented at ASCO GU meeting 2023 is to investigate cabozantinib activity after first line combination failure.
The study has been designed to assess activity and safety of cabozantinib single agent, so it's a Phase II, a non-randomized Phase II with two cohorts. Cohort A, patient who had failed nivolumab plus ipilimumab and Cohort B, patient who had failed VGF plus TKI regimen. What has been presented at this meeting is the interim analysis of CaboPoint study. This pre-plan analysis was designed to be performed when 80% of cohort bay had been enrolled and for which we had more than three months follow-up. So 88 patients are part of this analysis.
Primary endpoint is response rate, and the key message is that with cabozantinib single agent, we are able to reach a response rate of almost 30% divided in 32% in Cohort A and 25% in Cohort B. Of course, there was no new safety signal with cabozantinib single agent. This study is important because it is the first time we have cabozantinib pure second-line data after a doublet with an IO-based first-line regimen. What is needed now is to know with further follow-up the PFS and overall survival within this study, and that will be the subject of further analysis.
What we also would like to know, is there anything we should add on top of cabozantinib? And that's the topic of the CONTACT-03 study that is still pending to know if there is an added value of sustained PD-L1 inhibition, for instance. So to summarize, CaboPoint is the first prospective study of cabozantinib as a pure second line after combination therapy in first line, showing you response rates of 30% for a single-agent TKI. And it means our patient, including those who did progress under first line, should be offered a second line therapy.
Matt D. Galsky, MD, of the Icahn School of Medicine at Mount Sinai and Tisch Cancer Institute, discusses results from CheckMate 274, which investigated nivolumab compared with placebo in patients with bladder or upper urinary tract cancer, following radical surgery to remove invasive disease. (Abstract LBA443).
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).
Thomas Powles, MD, PhD, of Barts Health NHS Trust, Queen Mary University of London, discusses new data from the COSMIC-313 study of patients with advanced renal cell carcinoma of IMDC (International Metastatic RCC Database Consortium) intermediate or poor risk. Those who received cabozantinib instead of placebo with nivolumab and ipilimumab as first-line treatment seemed to experience improved progression-free survival. A subgroup analysis suggested the benefit was primarily in patients with an intermediate risk. Follow-up for overall survival is ongoing. (Abstract 605).
Sumanta K. Pal, MD, introduces his City of Hope colleagues, Hedyeh Ebrahimi, MD, MPH, who discusses the prevalence of dietary modification and supplement use in patients with metastatic renal cell carcinoma, and Daniela Castro, MSc, who discusses expanding eligibility criteria in kidney, prostate, and urothelial cancer trials to more accurately reflect the real-world population and reducing exclusion criteria. (Abstract 662, 612, 34, 453)
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).