POD1UM-303/InterAACT 2 Study

Anal cancer, while relatively rare, has seen a rising incidence in recent years. Approximately 40% of patients with anal cancer will either experience relapse following primary treatment or develop de novo metastatic disease. Prognosis for these patients remains poor, with limited therapeutic options and a diminished quality of life.

The primary objective of the POD1UM-303/InterAACT 2 study was to improve outcomes for these patients by building on the results of the previous InterAACT study, which had established carboplatin and paclitaxel as an effective chemotherapy regimen. The investigators aimed to assess the potential benefits of incorporating retifanlimab, a monoclonal anti-PD-1 antibody, into this established chemotherapy backbone. A total of 300 patients were enrolled and randomized in a 1:1 ratio to receive six months of carboplatin and paclitaxel in both arms. The randomization determined whether patients would additionally receive retifanlimab or a placebo for 12 months. Patients in the placebo arm had the option to cross over to receive single-agent retifanlimab in the event of disease progression.

There was a statistically significant improvement in PFS, the primary endpoint, with a median PFS of 7.4 months in the placebo group vs. 9.3 months in the retifanlimab group. The hazard ratio for PFS was 0.63, indicating a notable early and sustained separation of the survival curves, suggesting a consistent benefit for patients receiving retifanlimab throughout the follow-up period. Preliminary data from the interim analysis suggest a potential OS benefit, with an approximate six-month difference between the placebo and retifanlimab arms. While these OS data are not yet fully mature, the current trend further supports the efficacy of retifanlimab in combination with carboplatin and paclitaxel in this patient population.

The combination of retifanlimab with carboplatin and paclitaxel was generally well tolerated. As expected, there was a slight increase in immune-related adverse events in the retifanlimab arm, but these were manageable, with no novel or concerning safety signals observed. 

The early indication of a six-month survival benefit is promising, though longer follow-up is required to confirm whether this difference will further increase. The impact of patient crossover to retifanlimab treatment may influence final outcomes, but the current trend supports the potential efficacy of this combination therapy in improving survival outcomes for patients with advanced anal cancer.