Retifanlimab + Carboplatin/Paclitaxel Cuts Risk of Progression 37% Across All Subgroups in Advanced Anal Cancer (POD1UM-303)

In the POD1UM-303 phase 3 trial (NCT04472429), 308 patients with inoperable locally recurrent or metastatic SCAC were randomised 1:1 to retifanlimab (PD-1 Ab) + carboplatin/paclitaxel or placebo + chemotherapy. Median PFS was 9.3 mo vs 7.4 mo (HR 0.63, p = 0.0006); the benefit held in PD-L1 <1% tumors (HR 0.53), PD-L1 ≥1% (HR 0.64), liver-met-positive disease, HPV-positive and HIV-positive subgroups. Among 69 placebo patients who crossed over to single-agent retifanlimab at progression, ORR matched the earlier platinum-refractory POD1UM-202 study and median OS reached 24.3 mo, shorter than the 29.2 mo seen with first-line retifanlimab + chemo. Safety during crossover mirrored prior experience; no new grade ≥3 immune toxicities emerged. Historical carboplatin/paclitaxel alone (INTERAACT) yields PFS ~7–8 mo and OS ~20 mo, underscoring the added value of upfront PD-1 blockade.