Impact of concomitant medications on immune checkpoint inhibitor outcomes in sarcoma.

11553 Background: Immune checkpoint inhibitors (ICIs) are an established treatment for many malignancies, with an emerging role in sarcoma. While the impact of concomitant medications (CM) on ICIs has been described in other cancers, it has not been evaluated in sarcoma. We assessed the association between CM use and ICIs outcomes in sarcoma patients. Methods: This pooled post hoc analysis included 7 investigator-initiated phase II ICI-based trials enrolling patients with metastatic sarcoma between April 1, 2017, and May 30, 2024. Patients receiving ≥1 dose of ICIs were included. CM taken within 30 days prior to treatment initiation were defined as baseline; PRN medications were excluded. CM were recorded at each cycle through end of treatment and categorized by medication class; supplements/herbal agents included vitamins, minerals, probiotics, botanicals, amino acids, and other dietary substances. For progression-free survival (PFS), baseline and on-treatment CM were analyzed as time-dependent covariates using Cox proportional hazards models. Overall survival (OS) analyses were limited to baseline CM. Logistic regression evaluated associations between baseline CM and objective response (ORR) and immune-related adverse events (irAEs). Toxicity was graded per CTCAE v5.0. Results: A total of 321 patients (median age, 58 years) were included. The most common histologies were liposarcoma (all subtypes, 22%), undifferentiated pleomorphic sarcoma (22%), and leiomyosarcoma (19%); 46% had received ≥3 prior lines of therapy. ICI was combined with cytokine/oncolytic therapies (43%), targeted agents (38%), or chemotherapy (19%). After a median follow-up of 47.4 months, ORR was 18%, median PFS was 3.9 months (95% CI, 3.09–5.32), and median OS was 19.9 months (95% CI, 17.5–22.9). Grade ≥3 irAEs occurred in 25% of patients, most commonly hematologic (6%) and hepatic (5%). On-treatment use of supplements/herbal agents was associated with longer PFS (HR 0.64, 95% CI 0.50–0.82; p<0.01), while on-treatment anti-infective use was associated with shorter PFS (HR 1.55, 95% CI 1.06–2.25; p=0.02); baseline anti-infective use was not associated with PFS. Baseline supplement/herbal use was associated with longer OS (HR 0.69, 95% CI 0.53–0.90; p<0.01), whereas baseline non-opioid (HR 1.54, 95% CI 1.10–2.16; p=0.01) and opioid analgesic use (HR 2.14, 95% CI 1.45–3.14; p<0.01) were associated with shorter OS. Baseline antihistamine use showed a trend toward increased gastrointestinal irAEs (OR 2.37, 95% CI 0.97–5.98; p=0.06). No CM class was associated with ORR. Conclusions: Concomitant medication use is associated with differential ICI outcomes in metastatic sarcoma and warrants prospective evaluation. CM Timing Outcome HR SH OT PFS 0.64 AI OT PFS 1.55 AI BL PFS 1.37* SH BL OS 0.69 Non-OA BL OS 1.54 OA BL OS 2.14 *Not statistically significant; SH = Supplements/herbal agents, AI = Anti-infectives, OA = Opioid analgesia, OT = on-treatment, BL = Baseline.