The addition of retifanlimab to standard chemotherapy significantly improves progression-free survival in patients with inoperable, locally recurrent or metastatic squamous cell anal carcinoma (SCAC), according to results from the phase III POD1UM-303/InterAACT2 trial presented at the European Society for Medical Oncology (ESMO) Congress 2024. The study, which evaluated retifanlimab in combination with carboplatin and paclitaxel, demonstrated a clinically meaningful 37% reduction in the risk of cancer progression or death. These findings suggest a potential new standard of care for this rare and often-neglected disease.
Improved Progression-Free Survival
The POD1UM-303/InterAACT2 trial randomly assigned patients with previously untreated, inoperable locally recurrent or metastatic SCAC to receive either retifanlimab (500 mg intravenously every 4 weeks) or placebo, in combination with carboplatin and paclitaxel, for up to 6 months, followed by monotherapy for up to 1 year. The primary endpoint was progression-free survival (PFS), assessed by blinded independent central review.
The results showed that the median PFS was 9.3 months in the retifanlimab plus chemotherapy arm, compared to 7.4 months in the placebo plus chemotherapy arm (HR = 0.63, 95% CI = 0.47–0.84, P = .0006). This indicates a statistically significant and clinically relevant improvement in PFS with the addition of retifanlimab.
Overall Survival Trend
An interim analysis of overall survival (OS) data revealed a strong trend toward improved OS in the retifanlimab arm. Patients receiving retifanlimab in combination with chemotherapy achieved a median OS of 29.2 months, compared to 23.0 months in the placebo arm (HR = 0.70, 95% CI = 0.49–1.01, P = .0273). While the OS data are not yet mature, the observed 6-month improvement suggests a potential survival benefit with the combination therapy. The overall survival follow-up is ongoing.
Enhanced Response Rates and Duration
Blinded independent central review also demonstrated improvements in overall response rate (ORR) and duration of response (DoR) in the retifanlimab arm. The ORR was 56% (95% CI = 48%–64%) in the retifanlimab arm, compared to 44% (95% CI = 36%–52%) in the placebo arm. The median DoR was 14 months (95% CI = 8.6–22.2) in the retifanlimab arm, compared to 7 months (95% CI = 5.6–9.3) in the placebo arm. The disease control rate was 87% in the retifanlimab arm and 80% in the placebo arm.
Safety and Tolerability
Retifanlimab was generally well-tolerated, with a safety profile consistent with other chemotherapy plus checkpoint inhibitor regimens. The most common treatment-emergent adverse events in the retifanlimab plus chemotherapy arm were anemia (66.2%), nausea (56.5%), and alopecia (51.3%).
Expert Commentary
"The POD1UM-303/InterAACT2 trial is the first and largest phase III trial evaluating a checkpoint inhibitor for the treatment of patients with squamous cell anal carcinoma, a disease with significant medical need," said Pablo J. Cagnoni, MD, President and Head of Research and Development at Incyte. "The positive efficacy and safety data presented today at ESMO illustrate the potential of retifanlimab in combination with carboplatin and paclitaxel to become a new standard-of-care treatment for patients with advanced disease."
Sheela Rao, MD, a consultant medical oncologist at The Royal Marsden National Health Service Foundation Trust and lead author of the study, added, "I believe the positive results from the POD1UM-303/InterAACT2 trial may provide a long-awaited, new treatment option with retifanlimab in addition to platinum-based chemotherapy for adults with inoperable locally recurrent or metastatic squamous cell anal carcinoma."
Implications for Clinical Practice
The results of the POD1UM-303/InterAACT2 trial suggest that retifanlimab in combination with carboplatin and paclitaxel represents a potential new standard of care for patients with advanced SCAC. With limited treatment options currently available, this combination offers a clinically meaningful improvement in progression-free survival and a promising trend toward improved overall survival.
