key papersKey paper

POD1UM-303/InterAACT-2: retifanlimab with carboplatin and paclitaxel for locally recurrent or metastatic anal squamous cell carcinoma

Adding the PD-1 antibody retifanlimab to first-line carboplatin and paclitaxel for advanced anal cancer lengthened the time before the cancer progressed from 7.4 to 9.3 months and cut the risk of progression by 37 percent, with manageable extra toxicity.

Global double-blind randomised phase 3 trial: 308 patients with untreated inoperable locally recurrent or metastatic anal squamous cell carcinoma were randomised to carboplatin-paclitaxel with retifanlimab (154) or placebo (154).

Median progression-free survival was 9.3 months with retifanlimab against 7.4 months with placebo (hazard ratio 0.63, one-sided p 0.0006). Serious adverse events (47.4 against 38.8 percent) and grade 3 or worse adverse events (83.1 against 75.0 percent) were more frequent with retifanlimab; neutropenia and anaemia were the most common. One treatment-related fatal event (pancytopenia) occurred in the retifanlimab group.

Randomised controlled trialChanged practice308 participants

Authors

Rao S, Samalin-Scalzi E, Evesque L, et al.

Published

The Lancet, 2025

Full text

doi:10.1016/S0140-6736(25)00631-2 PubMed 40517007

Findings

Median progression-free survival 9.3 months (95% CI 7.5 to 11.3) versus 7.4 months (7.1 to 7.7); hazard ratio 0.63 (0.47 to 0.84), one-sided p 0.0006.
Serious adverse events 47.4 versus 38.8 percent; grade 3 or worse adverse events 83.1 versus 75.0 percent.
Grade 3 or worse neutropenia 35.1 versus 29.6 percent; anaemia 19.5 versus 20.4 percent.

What it means

Retifanlimab with carboplatin-paclitaxel is the new first-line standard for advanced anal squamous cell carcinoma; approved in the United States in May 2025.

Caveats