Evidence-Informed Decisions in SCAC Care: Subgroup Insights From POD1UM-303
A panelist discusses how the POD1UM-303 trial showed that no patient subpopulation was clearly excluded from benefiting from retifanlimab plus carboplatin/paclitaxel in terms of progression-free survival, though PD-L1-negative patients (representing only 10% of the study population) demonstrated a less robust overall survival signal compared to their positive progression-free survival benefit, suggesting that while PD-L1 status is not a validated exclusion biomarker, further research is needed to better understand the optimal benefit in PD-L1-negative patients given prior data showing lower response rates with PD-1 inhibitors in this subgroup.
Evidence-Informed Decisions in SCAC Care: Subgroup Insights From POD1UM-303
The POD1UM-303 trial demonstrated broad efficacy across patient subgroups, with no clear population excluded from benefiting from retifanlimab combination therapy. Forest plot analysis of progression-free survival data revealed consistent benefit patterns across various patient characteristics, with no subgroup showing lack of efficacy for the primary end point. However, certain subgroups represented smaller patient populations, which limited the statistical power to draw definitive conclusions about specific benefit patterns. The overall trial design and patient stratification provided valuable insights into treatment responses across different demographic and clinical characteristics, supporting the broad applicability of the combination regimen.
PD-L1 expression levels emerged as a notable biomarker for consideration, though not as an exclusionary factor for treatment selection. Only 10% of the trial population demonstrated PD-L1 negative status (less than 1% expression), creating a relatively small subgroup for analysis. While PD-L1 negative patients showed benefit in progression-free survival analysis, the overall survival signal appeared less robust in this population. The recently published Lancet results provide subgroup analysis data suggesting that PD-L1-negative patients may not derive the same magnitude of overall survival benefit, though this could potentially be attributed to the crossover design diluting survival signals.
Historical data from other PD-1 inhibitors in squamous cell anal carcinoma supports the concept that PD-L1 expression influences treatment response, with pembrolizumab studies demonstrating significantly lower response rates in PD-L1 negative advanced disease compared to PD-L1-positive tumors. However, the progression-free survival benefit observed in POD1UM-303 suggests that PD-L1 status should not serve as an absolute exclusion criterion for retifanlimab treatment. Instead, clinicians should consider PD-L1 status as part of a comprehensive risk-benefit assessment, recognizing that while PD-L1 negative patients may derive less robust overall survival benefits, they still demonstrate meaningful progression-free survival improvements that justify treatment consideration in appropriate clinical contexts.
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