Findings from the phase 3 PODIUM-303 study show the addition of retifanlimab to standard of care chemotherapy significantly extended median progression-free survival (PFS) vs chemotherapy alone for patients with previously untreated, locally recurrent or metastatic squamous cell carcinoma of the anal canal. 

These practice-changing results were presented by Sheela Rao, MBBS, MD, FRCP, The Royal Marsden NHS Foundation Trust, London, United Kingdom, at the 2024 ESMO Congress in Barcelona, Spain.

“Inoperable locally recurrent/metastatic squamous cell carcinoma of the anal canal is associated with suboptimal PFS and OS [overall survival], despite high initial response rates to platinum-based chemotherapy,” explained Dr Rao.

Retifanlimab is an anti–programmed cell death (PD)-1 monoclonal antibody and has demonstrated antitumor activity among patients with advanced squamous cell carcinoma of the anal canal who progressed on platinum-based chemotherapy. The phase 3, double-blind, controlled PODIUM-303 trial aimed to evaluate the addition of retifanlimab to standard of care chemotherapy for patients with previously untreated, locally recurrent or metastatic squamous cell carcinoma of the anal canal.

The primary end point was PFS by blinded independent central review per RECIST v1.1. Secondary end points included OS and safety.

The trial randomized patients in a 1:1 ratio to receive 6 cycles of standard-dose carboplatin-paclitaxel plus placebo or retifanlimab 500 mg every 4 weeks for up to 1 year with possibility of crossover. In total 308 patients were enrolled on the trial as of April 15, 2024. The median age of patients was 62 years (range, 29 to 86) and 72% were female, 87% were White, 4% were HIV-positive, and 36% had livers metastases.

The trial met its primary end point. Median PFS was 9.3 months in the retifanlimab arm vs 7.39 months in the placebo arm (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.47 to 0.84; P = .0006). In addition, researchers noted a strong trend of improved OS though the data is immature.

Regarding safety, researchers noted that retifanlimab was tolerable and reported no new safety signals to compromise or disrupt chemotherapy administration.

In conclusion, this phase 3 international study demonstrated encouraging efficacy and a favorable benefit/risk ratio for the addition of retifanlimab to standard of care chemotherapy for the first-line treatment of locally recurrent or metastatic squamous cell carcinoma of the anal canal, suggesting this combination as the new standard of care for this patient population.

Source:

Rao S, Samalin-Scalzi E, Evesque L, et al. POD1UM-303/InterAACT 2: Phase III study of retifanlimab with carboplatin-paclitaxel (c-p) in patients (Pts) with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC) not previously treated with systemic chemotherapy (Chemo). Presented at 2024 ESMO Congress. September 13-17, 2024. Abstract LBA2