Sumanta Pal, MD
Sumanta Pal, MD, of City of Hope, Duarte, California, praised the authors for the conduct of the study, but stopped short of endorsing nivolumab as standard of care.
“The phase III CheckMate 274 trial evaluated adjuvant nivolumab vs placebo in patients with high-risk, resected, muscle-invasive bladder cancer. Until now, there has been no obvious standard of care in the setting; multiple trials have assessed adjuvant chemotherapy but have suffered from poor accrual or pathologic issues. The investigator should be congratulated for completing a study in this setting, but adjuvant nivolumab should not necessarily pivot immediately to a standard of care,” he stated.
“The investigative community must consider the fact that there is a negative phase III trial in the same setting, the IMvigor010 study, which compared atezolizumab against observation with similar entry criteria. In that study, no benefit in disease-free survival or overall survival was observed.1 Furthermore, we still await overall survival data from CheckMate 274,” Dr. Pal continued.
Dr. Pal pointed out that within CheckMate 274, certain subsets appeared to drive the disease-free survival benefit. “This includes those patients who are PD-L1–positive. In addition, a close look at the forest plot suggests that patients with upper-tract disease may benefit to a lesser extent,” he noted.
“How can we potentially advance checkpoint inhibition within the field? First, we can look towards a tiebreaker study. The phase III Alliance AMBASSADOR study [ClinicalTrials.gov identifier NCT03244384] will explore adjuvant pembrolizumab vs observation in patients with high-risk muscle-invasive bladder cancer, a population similar to that in CheckMate 274. Another option, particularly in the face of perhaps less impressive data in the setting of upper-tract disease, is the PROOF 302 study [NCT04197986]. This is a phase III study comparing infigratinib, an FGFR3 inhibitor, to placebo in patients with relevant mutations,” Dr. Pal commented.
DISCLOSURE: Dr. Pal has served in a consulting or advisory role for Astellas Pharma, Aveo, Bristol Myers Squibb, Eisai, Exelixis, Genentech, Ipsen, Myriad Pharmaceuticals, Novartis, and Pfizer.
1. Bellmunt J, Hussain M, Gschwend JE: Adjuvant atezolizumab versus observation in muscle-invasive urothelial carcinoma (IMvigor010): A multicentre, open-label, randomized, phase 3 trial. Lancet Oncol. March 12, 2021 (early release online).
Adjuvant therapy with nivolumab, an anti–PD-1 immune checkpoint inhibitor, after radical surgery improved disease-free survival in high-risk muscle-invasive urothelial cancer regardless of PD-L1 status, according to the results of the CheckMate 274 randomized phase III trial presented at the 2021...