Results from the phase 3 POD1UM-303/InterAACT 2 trial have established retifanlimab (Zynyz) combined with carboplatin and paclitaxel as a new first-line treatment for advanced squamous cell carcinoma of the anal canal (SCAC). The findings led the FDA to approve the regimen in May 2025 for patients with inoperable recurrent or metastatic disease who have not received prior systemic chemotherapy.
The study showed that adding retifanlimab significantly improved outcomes compared with chemotherapy alone. Median progression-free survival increased from 7.4 to 9.3 months, overall survival improved from 22.2 to 32.8 months, and the duration of response doubled from 7 to 14 months.
Experts note that retifanlimab provides an effective maintenance option after chemotherapy is stopped due to cumulative side effects such as neuropathy. Using immunotherapy in the first-line setting appears more beneficial than waiting until later treatment. However, patients whose disease progresses on retifanlimab are unlikely to benefit from other PD-1–based therapies, highlighting the need for new second-line treatment options, including antibody-drug conjugates, novel immunotherapies, and cellular therapies.