Durability, Patient Selection, and the Role of Biomarkers

This segment focuses on the durability of benefit with first-line chemo-immunotherapy in advanced SCAC and how the POD1UM-303 findings are shaping real-world treatment decisions. Beyond improving response rates, a key advantage of adding retifanlimab appears to be the durability of responses. In the trial, chemotherapy was limited to 6 months, after which patients continued maintenance with immunotherapy or placebo. Despite this limited chemotherapy exposure and allowance for crossover, median duration of response doubled with upfront immunotherapy (approximately 14 months vs 7 months), likely contributing to the substantial OS benefit observed.

The discussion emphasizes that early integration of immunotherapy is critical. When immune checkpoint inhibitors are used in later lines, response rates are typically around 10%, and meaningful survival gains are less evident. In contrast, combining immunotherapy with chemotherapy upfront not only increases the likelihood of response but also enables a subset of patients to achieve prolonged disease control.

Despite these advances, predicting which patients will derive the greatest benefit remains challenging. PD-L1 expression did not meaningfully influence outcomes in POD1UM-303 and is not currently used to guide treatment selection. As a result, most patients with newly diagnosed advanced disease are treated with carboplatin, paclitaxel, and retifanlimab, provided there are no contraindications.

Clinical judgment remains essential, with treatment decisions based on performance status, comorbidities, and immune-related risk factors. Active autoimmune disease or prior organ transplantation may preclude immunotherapy, whereas well-controlled autoimmune conditions or controlled HIV infection may still be compatible with treatment.

Although a broad first-line chemo-immunotherapy approach can be used, better predictive biomarkers are needed.