The FDA approved retifanlimab in combination with carboplatin/paclitaxel for the treatment of advanced squamous cell anal cancer (SCAC) in May 2025, marking a significant advancement in immunotherapy integration for this rare malignancy. The approval was based on results from the PODIUM-303 study, which demonstrated superior efficacy outcomes when the checkpoint inhibitor was added to standard chemotherapy.
PODIUM-303 Trial Results Drive Regulatory Approval
The pivotal PODIUM-303 study showed that adding retifanlimab to carboplatin/paclitaxel improved progression-free survival to 9.3 months compared to 7.4 months with chemotherapy alone. Response rates also increased significantly, reaching 56% with the combination versus 44% with carboplatin/paclitaxel alone. These results led to the FDA's approval of the immunotherapy combination as a new first-line treatment option for patients with advanced anal cancer.
Updated Treatment Guidelines Reflect New Evidence
Current NCCN guidelines for advanced anal cancer have been updated to include carboplatin/paclitaxel plus retifanlimab as a category 2B evidence-based approach. The guidelines continue to recommend carboplatin/paclitaxel as the preferred first-line regimen, with additional options including modified FOLFOX and 5-FU–based combinations. The modified ECF regimen has also shown promising response rates in phase 2 studies.
For second-line and subsequent therapy, multiple checkpoint inhibitors are listed as preferred regimens for patients who have not received prior immunotherapy, including dostarlimab, nivolumab, pembrolizumab, and retifanlimab. Notably, not all listed agents have been specifically studied in anal cancer, representing an interesting aspect of guideline development.
Foundation Built on InterAACT Study Success
The current treatment landscape was established by the InterAACT study, which demonstrated that carboplatin/paclitaxel achieved similar response rates to cisplatin/5-FU (57% vs 59%) while providing improved progression-free survival, overall survival, and significantly better tolerability. This study established carboplatin/paclitaxel as the standard of care for advanced anal cancer, setting the stage for subsequent immunotherapy combinations.
Clinical Management Considerations
The integration of immunotherapy into anal cancer treatment represents an evolution from traditional chemotherapy approaches. The PODIUM-303 results suggest that checkpoint inhibition may enhance the efficacy of standard chemotherapy regimens, potentially offering patients improved outcomes with manageable toxicity profiles.
The approval of retifanlimab plus carboplatin/paclitaxel provides oncologists with a new evidence-based option for treating advanced squamous cell anal cancer, a disease where treatment options have historically been limited. The combination approach reflects the broader trend toward incorporating immunotherapy into standard cancer care regimens across multiple tumor types.
