Retifanlimab with carboplatin and paclitaxel for locally recurrent or metastatic squamous cell carcinoma of the anal canal (POD1UM-303/InterAACT-2): a global, phase 3 randomised controlled trial

Area of Science:

• Oncology
• Immunotherapy
• Clinical Trials

Background:

• Retifanlimab shows activity in programmed death ligand 1-positive advanced squamous cell anal carcinoma (SCAC) post-platinum chemotherapy.
• A prospective assessment was conducted to evaluate the addition of retifanlimab to initial carboplatin-paclitaxel therapy for SCAC.

Purpose of the Study:

• To prospectively assess the clinical benefit of adding retifanlimab to first-line carboplatin-paclitaxel chemotherapy in patients with advanced SCAC.

Main Methods:

• A global, multicentre, double-blind, randomised, controlled, phase 3 trial enrolled patients (≥18 years) with inoperable, locally recurrent, or metastatic SCAC.
• Patients received either retifanlimab or placebo every 4 weeks, combined with standard carboplatin-paclitaxel for up to 1 year.
• The primary endpoint was progression-free survival, assessed per Response Evaluation Criteria in Solid Tumours version 1.1.

Main Results:

• 308 patients were randomized; median progression-free survival was 9.3 months with retifanlimab vs. 7.4 months with placebo (hazard ratio 0.63; p=0.0006).
• Serious adverse events (grade ≥3) were more frequent with retifanlimab (83.1%) compared to placebo (75.0%).
• Most common grade ≥3 adverse events included neutropenia and anemia; four fatal adverse events occurred in the retifanlimab group, one deemed treatment-related.

Conclusions:

• Retifanlimab addition to first-line chemotherapy demonstrated clinical benefit in advanced SCAC with a manageable safety profile.
• The combination of retifanlimab with carboplatin and paclitaxel is suggested as a potential new standard of care for advanced SCAC.