2A global phase III trial has shown that adding retifanlimab to standard carboplatin and paclitaxel chemotherapy improves outcomes for patients with advanced squamous cell anal cancer. The POD1UM-303/InterAACT-2 study is the first large phase III trial in this setting. Results showed meaningful improvements in progression-free survival (PFS), overall survival (OS), and tumour control. The findings were published in The Lancet on 14 June 2025.
Anal Cancer and Unmet Needs
Squamous cell anal cancer makes up about 2.5% of gastrointestinal cancers. Its incidence has increased by 3% per year, mainly due to HPV infection. HIV-positive individuals are 25–35 times more likely to develop this cancer. About 14% of patients are metastatic at diagnosis, and nearly 40% relapse after chemoradiation. Five-year survival for metastatic cases is around 36%. No phase III systemic therapy trials had been completed before this study.
Study Design and Patients
The trial enrolled 308 patients with inoperable, locally advanced, or metastatic disease from 12 countries. Patients had not received prior systemic therapy and had good performance status. They were randomized 1:1 to receive retifanlimab 500 mg IV or placebo every four weeks, combined with carboplatin/paclitaxel for up to one year.
Key Results
Median PFS was 9.3 months in the retifanlimab group vs 7.4 months in the placebo group (HR 0.63; p = 0.0006). Kaplan-Meier curves for PFS and OS separated early and remained apart. Serious and grade ≥3 adverse events were more frequent with retifanlimab (83.1% vs 75.0%). Common side effects included neutropenia and anaemia. Four treatment-related deaths occurred in the retifanlimab group, one linked to therapy.
Clinical Significance
This study provides a new benchmark for treating advanced anal cancer. Experts noted the survival benefit is valuable, as options for later treatment are limited. These results support adding immunotherapy to standard chemotherapy in this setting. Future trials, including combinations with nivolumab and biomarker research, are ongoing.
The study was funded by Incyte and highlights the growing role of immunotherapy in HPV-related cancers.
