In a phase III trial (POD1UM-303/InterAACT-2) reported in The Lancet, Rao et al investigated the survival benefit of adding the PD-1 inhibitor retifanlimab to carboplatin-paclitaxel in patients with locally recurrent or metastatic squamous cell carcinoma of the anal canal.
Study Details
In the double-blind trial, 308 patients with no prior systemic treatment from sites in 12 countries across the European Union, Australia, the United Kingdom, and the United States were randomly assigned between November 2020 and July 2023 to receive retifanlimab at 500 mg (n = 154) or placebo (n = 154) every 4 weeks plus standard carboplatin-paclitaxel for up to 1 year. Patients with well-controlled HIV disease were eligible. A total of 72% of enrolled patients were female. Patients in the control group could cross over to receive retifanlimab monotherapy upon disease progression. The primary endpoint of the study was independently assessed progression-free survival.
Key Findings
Median progression-free survival was 9.3 months (95% confidence interval [CI] = 7.5–11.3 months) in the retifanlimab group vs 7.4 months (95% CI = 7.1–7.7 months) in the control group (hazard ratio [HR] = 0.63, 95% CI = 0.47–0.84, P = .0006).
A total of 69 patients (45%) in the control group crossed over to receive retifanlimab monotherapy on progression.
At time of progression-free survival analysis, median overall survival was 29.2 months (95% CI = 24.2 months to not evaluable) in the retifanlimab group vs 23.0 months (95% CI = 15.1–27.9 months) in the control group. Despite the relative immaturity of the overall survival data and the high proportion of control group patients who crossed over to receive retifanlimab, there was evidence of survival benefit in the retifanlimab group (HR = 0.70, 95% CI = 0.49–1.01).
Grade ≥ 3 adverse events occurred in 83.1% of patients in the retifanlimab group and 75.0% of the control group, most commonly neutropenia (35.1% vs 29.6%) and anemia (19.5% vs 20.4%). Serious adverse events occurred in 47.4% vs 38.8% of patients. Immune-related adverse events occurred in 49% vs 26% of patients; most were grade 1 or 2, and none led to treatment discontinuation. A treatment-related death occurred in the retifanlimab group (due to pancytopenia).
The investigators concluded: “Retifanlimab provides clinical benefit, with a manageable safety profile, when added to first-line chemotherapy in advanced squamous cell carcinoma of the anal canal. These results suggest retifanlimab with carboplatin plus paclitaxel should be considered as the new standard of care for patients with advanced squamous cell anal carcinoma.”
Sheela Rao, MD, of the Royal Marsden Hospital NHS Foundation Trust, Sutton, Surrey, UK, is the corresponding author for The Lancet article.
Disclosure: The study was funded by Incyte. For full disclosures of all study authors, visit The Lancet.
