Carboplatin/Paclitaxel to Immunotherapy Combinations: Evolving First-Line Options in Advanced SCAC

Advanced Disease Management Guidelines

Current NCCN guidelines for advanced anal cancer recommend carboplatin/paclitaxel as the preferred first-line regimen, with additional options including modified FOLFOX and 5-FU–based combinations. The recent addition of carboplatin/paclitaxel plus retifanlimab (a checkpoint inhibitor) represents a category 2B evidence-based approach that may evolve with emerging data. The modified ECF regimen has also shown promising response rates in phase 2 studies.

Second-line and subsequent therapy options include chemotherapy regimens not used in first-line treatment, with multiple checkpoint inhibitors listed as preferred regimens for patients who have not received prior immunotherapy. These include dostarlimab, nivolumab, pembrolizumab, and retifanlimab; notably, not all listed agents have been specifically studied in anal cancer, representing an interesting aspect of guideline development.

The InterAACT study established carboplatin/paclitaxel as standard care by demonstrating similar response rates (57% vs 59%) but improved progression-free survival, overall survival, and significantly better tolerability compared with cisplatin/5-FU. The PODIUM-303 study further advanced the field by showing improved PFS (9.3 vs 7.4 months) and response rates (56% vs 44%) with the addition of retifanlimab to carboplatin/paclitaxel, leading to FDA approval in May 2025.