Concomitant Medication Effects on Immunotherapy Outcomes in Sarcoma: A Pooled Post Hoc Analysis of Seven Phase II Trials
Adel Shahnam, Kristen DiConza, Simran Jasnani, Rhoena Desir‐Camille, Evan Rosenbaum, Olayode Babatunde, Ciara M. Kelly, Lauren B. Banks, Viswatej Avutu, Ping Chi, Sujana Movva, Mark A. Dickson, Mrinal M. Gounder, Mary L. Keohan, Robert G. Maki, William D. Tap, Sandra P. D'AngeloABSTRACT
Background
Concomitant medications (CMs) influence outcomes in patients receiving immune checkpoint inhibitors (ICIs), but their impact in sarcoma remains undefined. We assessed the association between CM use and ICI outcomes in patients with advanced or metastatic sarcoma.
Methods
This pooled analysis included patients from seven investigator‐initiated phase II trials of ICI‐based therapy for sarcoma. CMs within 30 days of treatment were defined as baseline; on‐treatment exposure was captured longitudinally. The primary endpoint was progression‐free survival (PFS); secondary endpoints included overall survival (OS), objective response rate (ORR), and immune‐related adverse events (irAEs). Multivariable Cox models adjusted for age, ECOG performance status, histological subtype, treatment regimen, and race.
Results
Among 321 patients (median follow‐up: 47.4 months), in time‐dependent analyses, exposure to anti‐infective medications was associated with shorter PFS (adjusted hazard ratio [aHR] 1.54, 95% CI 1.05–2.27). Baseline use of vitamins/minerals/supplements/herbal products was associated with longer PFS (aHR 0.73, 95% CI 0.56–0.95) and OS (aHR 0.67, 95% CI 0.51–0.89). Baseline statin use was associated with longer PFS (aHR 0.64, 95% CI 0.47–0.87) but not OS. Baseline use of opioids was associated with shorter OS (aHR 1.71, 95% CI 1.12–2.61). No CM class was significantly associated with ORR or irAE occurrence.
Conclusions
CM use is associated with differential efficacy outcomes in sarcoma patients receiving ICIs. These findings highlight the need for prospective studies to define the impact of commonly prescribed medications on ICI outcomes and to optimize clinical trial stratification.