Aspirin use and outcomes with immune checkpoint inhibitors in metastatic cancer.

e14584 Background: Aspirin (ASA) may modulate antitumor immunity. We evaluated the association between concomitant ASA use and outcomes in metastatic cancers treated with immune checkpoint inhibitors (ICI). Methods: We conducted a population-based cohort study of patients with metastatic cancers treated with ICIs from January 2015 to December 2024, stratified by concomitant ASA use (users vs non-users). ASA treatment was described as 100 mg aspirin continuously through therapy. In this series, the indication for ASA was: prophylaxis for coronary artery disease (CAD) or CAD-equivalent conditions and/or comorbidities. The primary endpoint was OS, and the secondary endpoints were PFS, ORR, and DCR. Results: Among 347 ICI-treated patients, ASA exposure status was available for 338 patients (82 users, 256 non-users); median age at ICI initiation was 63.6 years (IQR: 55.7–70.4), and 25.9% were female. The most recorded cancers were NSCLC (34.9%), RCC (25.1%), melanoma (14.4%), bladder cancer (9.2%), and SCLC (6.6%), with the remaining cancers accounting for 9.8%. ICI exposures were nivolumab (58.2%), pembrolizumab (21.3%), atezolizumab (7.8%), ipilimumab (6.6%), nivolumab–ipilimumab (2.6%), avelumab (2.6%), and durvalumab (0.9%). ASA users and non-users were generally well-balanced across malignancy and treatment distributions, baseline sites of metastasis, and ECOG PS; ASA users were older at the time of ICI commencement (median 66.6 vs 62.4 years; p = 0.001). Median PFS was 11.1 months (95% CI 8.2–14.1) and 3.9 months (95% CI 2.9–5.0) for ASA users vs non-users (p = 0.001). On multivariate analysis, ASA use (HR 0.565; 95% CI: 0.388–0.823; p = 0.003) and ECOG PS 0–1 (HR 0.330; 95% CI: 0.193–0.567; p < 0.001) were independent predictors of a favorable PFS outcome. The median follow-up for OS was 17.8 months (95% CI: 15.3-20.3). Median OS was 36.1 months (95% CI 11.9–60.2) in users as contrasted with 15.7 months (95% CI 11.1–20.3) in non-users (p = 0.047). ASA use (HR 0.597, 95% CI 0.379-0.939; p = 0.026) and ECOG PS 0-1 (HR 0.406, 95% CI 0.262–0.631; p < 0.001) were independently correlated with improved OS on a multivariable analysis whereas baseline lung metastases (HR 1.643, 95% CI 1.062–2.542; p = 0.025) and baseline liver metastases (HR 2.242, 95% CI 1.443–3.483; p < 0.001) were associated with worse OS. In the response-evaluable cohort (n = 240), ORR was 55.7% (34/61) in users vs 44.1% (79/179) in non-users (p = 0.117), and DCR was 83.6% (51/61) vs 62.6% (112/179), respectively (p = 0.002). Conclusions: Among patients with ICI-treated metastatic cancer, aspirin use was associated with longer PFS and OS, as well as higher DCR. These findings require prospective validation to ascertain causality, patient selection, and the safety–benefit profile of aspirin with ICIs.