The phase 3 POD1UM-303 trial has demonstrated that the addition of retifanlimab to carboplatin and paclitaxel chemotherapy significantly improves progression-free survival (PFS) in patients with locally recurrent or metastatic squamous cell anal carcinoma (SCAC). These findings, presented at the 2024 ESMO Congress, suggest that retifanlimab could become a new standard of care for this patient population.
Improved Progression-Free Survival
The POD1UM-303 trial (NCT04472429) enrolled patients with locally recurrent or metastatic SCAC who had not previously received chemotherapy in the advanced setting. Patients were randomized 1:1 to receive either carboplatin and paclitaxel chemotherapy plus retifanlimab or chemotherapy plus placebo. The primary endpoint of the study was PFS.
The results showed a significant improvement in median PFS, from 7.4 months in the placebo arm to 9.3 months in the retifanlimab arm (HR, 0.63; 95% CI, 0.47-0.84; P = .0006). This improvement highlights the potential of retifanlimab to extend the time before disease progression in these patients.
Overall Survival and Response Rates
Interim analysis of overall survival (OS) also indicated a trend towards improvement with the addition of retifanlimab. The median OS was 29.2 months in the retifanlimab arm compared to 23.0 months in the placebo arm. While these data are still immature, the trend suggests a potential survival benefit with the combination therapy.
Furthermore, the overall response rate (ORR) was higher in the retifanlimab arm (56%) compared to the placebo arm (44%). This indicates that more patients experienced tumor shrinkage with the addition of retifanlimab to chemotherapy.
Safety and Tolerability
The addition of retifanlimab to chemotherapy was generally well tolerated. As expected, there was an increase in immune-related adverse effects, but these were manageable and did not compromise the delivery of chemotherapy. The treatment did not lead to significant dose reductions or delays.
Addressing Unmet Needs in SCAC
SCAC is an HPV-driven cancer, and its incidence rates are rising. Relapse after primary treatment with chemoradiotherapy is common, and the standard of care has not changed significantly since the early 1980s. There are currently no FDA-approved treatments for patients with advanced disease.
The success of the POD1UM-303 trial represents a significant advancement in the treatment of SCAC. The planned filing of a supplemental biologics license application (sBLA) for retifanlimab is underway, offering hope for addressing the unmet needs in this patient population.
Future Research Directions
Further research is needed to understand biomarkers that may predict response to retifanlimab and to determine the optimal duration of immunotherapy. Studies are also needed to explore treatment options after first-line immunotherapy and chemotherapy, including novel targeted agents.
