Use of PCSK9 Inhibitors Among Patients Receiving Immune Checkpoint Inhibitors for Cancer

Importance: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition enhances antitumor efficacy of immune checkpoint inhibitors (ICIs) in preclinical models, but clinical evidence remains limited. Objective: To compare survival and selected clinical outcomes among adults receiving ICIs for cancer who were treated with a PCSK9 inhibitor (PCSK9I) compared with high-intensity statin therapy. Design, Setting, and Participants: This comparative effectiveness study used deidentified data from the TriNetX research network. Adults with non-small cell lung cancer, melanoma, or renal cell carcinoma who received a programmed cell death 1 or a programmed cell death ligand 1 inhibitor between January 1, 2016, and December 31, 2024, were included. Follow-up began from ICI treatment initiation through January 13, 2026. Exposure: Patients with PCSK9I exposure within 1 year before ICI treatment initiation were compared with those receiving high-intensity statins without PCSK9I use. One-to-one propensity score matching was performed, followed by Kaplan-Meier and Cox proportional hazards regression analyses. Main Outcomes and Measures: Primary outcomes were overall survival and a modified 4-point major adverse cardiovascular event (MACE) composite. Secondary outcomes included use of acute health care services (emergency department visits, hospitalization, and critical care services). Results: Among 239 matched pairs of patients (478 patients; 273 [57.1%] male; mean [SD] age, 70.8 [8.5] years), the mean (SD) age was 70.7 (8.2) years in the PCSK9I cohort and 70.8 (8.7) years in the statin cohort; lung cancer was the most common malignant neoplasm (159 [66.5%] vs 150 [62.8%], respectively). During follow-up as long as 9 years, 99 deaths occurred in the PCSK9I cohort and 129 in the statin-only cohort. PCSK9I use was associated with improved survival (hazard ratio [HR], 0.69; 95% CI, 0.53-0.90; log-rank P = .006), with 2-year survival probabilities of 62% vs 51%. MACE did not differ significantly (73 vs 81 events; HR, 0.85; 95% CI, 0.62-1.16; P = .31). PCSK9I use was also associated with lower risks of emergency department visits (HR, 0.65; 95% CI, 0.49-0.86; P = .002), hospitalization (HR, 0.73; 95% CI, 0.57-0.92; P = .008), and use of critical care services (HR, 0.68; 95% CI, 0.48-0.96; P = .03). Conclusions and Relevance: Among adults with non-small cell lung cancer, melanoma, or renal cell carcinoma receiving ICIs, PCSK9I use was associated with improved survival and reduced levels of acute health care utilization without significant differences in cardiovascular events, warranting further prospective investigation.