The addition of retifanlimab (Zynyz) to carboplatin and paclitaxel significantly improved progression-free survival (PFS) in patients with recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC) who had not received prior chemotherapy. The phase 3 POD1UM-303/InterAACT 2 study, presented at the 2024 European Society for Medical Oncology (ESMO) Congress, demonstrated a clinically meaningful benefit, potentially establishing a new standard of care for this patient population.
Improved Progression-Free Survival
The POD1UM-303 trial (NCT04472429) revealed that patients treated with retifanlimab in combination with carboplatin and paclitaxel (n = 154) achieved a median PFS of 9.3 months (95% CI, 7.5-11.3) as assessed by blinded independent central review (BICR). In contrast, patients receiving placebo plus carboplatin and paclitaxel (n = 154) had a median PFS of 7.4 months (95% CI, 7.1-7.7; HR, 0.63; 95% CI, 0.47-0.84; P = .0006). The median follow-up times for PFS were 7.6 months (range, 0.0-33.9) and 7.1 months (range, 0.0-27.4), respectively.
Enhanced Overall Response and Duration of Response
Furthermore, the retifanlimab arm showed an overall response rate (ORR) of 56% (95% CI, 48%-64%), including a complete response (CR) rate of 22%. The placebo arm had an ORR of 44% (95% CI, 36%-52%) with a 14% CR rate (P = .0129). The median duration of response (DOR) was 14.0 months (95% CI, 8.6-22.2) in the retifanlimab arm compared to 7.2 months (95% CI, 5.6-9.3) in the placebo arm. Disease control rates were 87% (95% CI, 81%-92%) and 80% (95% CI, 73%-86%), respectively.
Overall Survival Trends
Interim overall survival (OS) analysis indicated a median OS of 29.2 months (95% CI, 24.2-NE) in the retifanlimab arm versus 23.0 months (95% CI, 15.1-27.9) in the placebo arm (HR, 0.70; 95% CI, 0.49-1.01; P = .0273). After adjusting for patient crossover, the median OS was 29.2 months (95% CI, 24.2-NE) and 19.1 months (95% CI, 13.4-27.9), respectively (HR, 0.63; 95% CI, 0.44-0.90; P = .0055).
Study Design and Patient Population
The POD1UM-303/InterAACT 2 trial was a global, double-blind study involving patients with inoperable locally recurrent or metastatic SCAC who had not received prior systemic chemotherapy. Patients were randomized 1:1 to receive either intravenous retifanlimab at 500 mg every 4 weeks for 12 months or placebo, both in combination with standard doses of carboplatin and paclitaxel for 6 months. The primary endpoint was PFS, with secondary endpoints including OS, ORR, DOR, safety, and pharmacokinetics.
Safety Profile
Treatment-emergent adverse effects (TEAEs) of any grade occurred in all patients in both arms. Grade 3 or higher TEAEs were observed in 83.1% of patients in the retifanlimab arm and 75.0% in the placebo arm. Common grade 3 or higher TEAEs included neutropenia, anemia, and decreased neutrophil count. Immune-related adverse effects were more frequent in the retifanlimab arm, with common events including peripheral sensory neuropathy, hypothyroidism, and hyperthyroidism.
Clinical Implications
According to Dr. Sheela Rao, a consultant medical oncologist at the Royal Marsden Hospital NHS Foundation Trust, retifanlimab plus carboplatin and paclitaxel represents a potential new reference treatment for advanced SCAC. This combination has the potential to address a significant unmet need in a disease where the standard of care has remained unchanged for decades.
