Background
Phase III randomized, double-blind, placebo-controlled trial with an optional crossover, N=308 systemic-treatment-naive adults with advanced or metastatic squamous-cell carcinoma of the anal canal (SCAC). Conducted in Europe, Australia, Japan, the UK and the US. The primary analysis established a PFS advantage; this is the final overall-survival analysis with crossover-adjusted, subgroup, and exploratory data.
Interventions and follow up
Arm A (n=154): Retifanlimab + carboplatin-paclitaxel
Arm B (n=154): Placebo + carboplatin-paclitaxel; 77 patients crossed over to retifanlimab monotherapy at progression
Primary endpoint: Progression-free survival; Key secondary endpoint: Overall survival
Median follow up: NR in abstract
Arm B (n=154): Placebo + carboplatin-paclitaxel; 77 patients crossed over to retifanlimab monotherapy at progression
Primary endpoint: Progression-free survival; Key secondary endpoint: Overall survival
Median follow up: NR in abstract
Results
Progression-free survival (updated): HR 0.62, 95% CI 0.47-0.81, nominal P=.0002
Overall survival: Median 32.8 vs 22.2 months, HR 0.75, 95% CI 0.55-1.01, P=.0305
Overall response rate: 56.5% vs 44.8%
Disease-control rate: 87.7% vs 80.5%
Crossover-adjusted OS: Consistent with the unadjusted analysis
Subgroups: Consistent OS benefit across all prespecified subgroups
Overall survival: Median 32.8 vs 22.2 months, HR 0.75, 95% CI 0.55-1.01, P=.0305
Overall response rate: 56.5% vs 44.8%
Disease-control rate: 87.7% vs 80.5%
Crossover-adjusted OS: Consistent with the unadjusted analysis
Subgroups: Consistent OS benefit across all prespecified subgroups
Adverse events
Overall: No new safety signals or trends identified versus the primary analysis
Detail: Grade ≥3 AE rates, discontinuation rates, and treatment-related deaths NR in the abstract; immune-related events consistent with the known retifanlimab profile
Detail: Grade ≥3 AE rates, discontinuation rates, and treatment-related deaths NR in the abstract; immune-related events consistent with the known retifanlimab profile
Conclusions
The final analysis confirms a clinically meaningful, durable benefit of adding retifanlimab to carboplatin-paclitaxel as first-line treatment of inoperable, locally recurrent or metastatic SCAC, establishing the combination as a new reference standard of care for this population.
Key Limitations
~50% crossover from placebo to retifanlimab monotherapy at progression may have diluted the unadjusted OS effect; PFS reported as a nominal P value (outside the OS statistical hierarchy); detailed AE data not reported in the abstract.
Clinical Context
Builds on the POD1UM-303 primary analysis (Rao S et al, Lancet 2025; PMID 40517007) by establishing OS as well as PFS benefit from frontline PD-1 blockade with carboplatin-paclitaxel in advanced anal cancer — previously a disease with no immunotherapy-based standard. Retifanlimab received FDA accelerated approval with carboplatin-paclitaxel for first-line locally recurrent/metastatic SCAC; these final-OS data support full approval and incorporation into ESMO guidance, displacing the prior carboplatin-paclitaxel-alone standard (InterAACT-1).