Survival outcomes in POD1UM-303/InterAACT-2: a phase III study of retifanlimab plus carboplatin-paclitaxel in first-line advanced squamous anal cancer.

In the primary analysis of the POD1UM-303/InterAACT 2 trial, median progression-free survival (PFS) was significantly longer with retifanlimab plus carboplatin-paclitaxel than with placebo plus carboplatin-paclitaxel in adult, systemic treatment-naïve patients with advanced/metastatic squamous cell carcinoma of the anal canal (SCAC). In this article, the final overall survival (OS) data from PODIUM-303/InterAACT 2, along with subgroup and exploratory analyses, are presented. POD1UM-303/InterAACT-2 was a phase III, randomized, double-blind, controlled, multicenter trial with an optional crossover period undertaken in Europe, Australia, Japan, the UK, and the United States. The primary endpoint was PFS, and OS was the key secondary endpoint.

Other endpoints included response, safety, and exploratory subgroup analyses. A total of 308 patients were randomly assigned (n = 154 for each of the retifanlimab plus carboplatin-paclitaxel and placebo plus carboplatin-paclitaxel groups), and 77 patients in the placebo plus carboplatin-paclitaxel group crossed over to receive retifanlimab monotherapy. When retifanlimab plus carboplatin-paclitaxel was compared with placebo plus carboplatin-paclitaxel in the updated efficacy analysis, there was a continued PFS benefit [hazard ratio (HR) 0.62, 95% confidence interval (CI) 0.47-0.81, nominal P = 0.0002] and a consistent and clinically meaningful improvement in OS (HR 0.75, 95% CI 0.55-1.01, P = 0.0305); median OS was 32.8 versus 22.2 months. Overall response rate was 56.5% versus 44.8%, and disease control rates were 87.7% versus 80.5%.

The results of the crossover-adjusted analysis were consistent with the main analysis, and there was a consistent OS benefit in favor of retifanlimab plus carboplatin-paclitaxel in all subgroups analyzed. No new safety signals or trends were reported. This final analysis confirms the benefits of retifanlimab plus chemotherapy in SCAC.

The results suggest that retifanlimab represents a new reference treatment and standard of care for patients with inoperable, locally recurrent, or metastatic SCAC.