POD1UM-303: Retifanlimab Plus Chemotherapy Improves PFS in Metastatic Squamous Cell Carcinoma of the Anal Canal

Despite high initial response rates to platinum-based chemotherapy, inoperable, locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC) is still associated with poor progression-free survival (PFS) and overall survival (OS) outcomes.

The POD1UM-303 (InterAACT 2) phase 3 trial sought to assess the efficacy and safety of adding retifanlimab, a PD-1 inhibitor, to standard carboplatin-paclitaxel (C-P) chemotherapy in patients with inoperable, locally recurrent or metastatic SCAC.

Conducted in a treatment-naive population, the study aimed to determine whether the addition of immunotherapy could improve PFS, a key challenge in this setting, where current platinum-based therapies have suboptimal long-term outcomes.

The findings were presented at the European Society for Medical Oncology Congress 2024 by lead study author Sheela Rao, MD, MBBS, FRCP, of the Gastrointestinal Unit at the Royal Marsden Hospital in London, UK.

A total of 308 patients were randomized 1:1 to receive either retifanlimab 500 mg every four weeks plus C-P (R arm) or C-P plus placebo (P arm) for up to six cycles, with an option for crossover. The primary endpoint was PFS by blinded independent central review per RESIST v1.1, and secondary endpoints were OS, objective response rate (ORR), disease control rate (DCR), duration of response (DoR), safety, and pharmacokinetics (PK).

The trial met its primary endpoint, with the retifanlimab combination significantly improving median PFS to 9.3 months compared to 7.4 months with C-P alone (hazard ratio [HR] 0.63, 95% CI, 0.47-0.84; P=.0006). Although the OS data were still immature, the trial showed a trend toward improved OS with retifanlimab (29.2 months versus 23 months; HR 0.70, P=.0273). In addition, the ORR was higher in the retifanlimab arm (55.8% vs 44.2%; P=.0129), and the DCR was also improved (87% vs 79.9%).

Retifanlimab was well tolerated, with no new safety signals emerging. The incidence of grade 3-5 treatment-related adverse events was comparable between the two groups, suggesting that adding retifanlimab does not significantly compromise the safety of the chemotherapy regimen.

The POD1UM-303 study demonstrated that the addition of retifanlimab to carboplatin-paclitaxel significantly improves PFS and ORR in patients with locally recurrent/metastatic SCAC. The study authors noted that the trial “demonstrates encouraging efficacy and favourable benefit/risk ratio for retifanlimab plus SoC chemo as first-line treatment of locally recurrent/metastatic SCAC and suggests a new SoC.”