Introduction
Recently, published studies have sparked discussion about combining statins with immune checkpoint inhibitors during cancer treatment. The Journal of Clinical Oncology (JCO) Oncology Practice recently published an editorial, “Abstract Thinking and Statins With Immune Checkpoint Inhibitors: Enough to Change Clinical Practice?,” and a meta-analysis, “Concomitant Statin Use and Survival in Patients With Cancer on Immune Checkpoint Inhibitors: A Meta-Analysis,” with variations in perspective.
Research suggests statins suppress PD-L1 expression in addition to their lipid-lowering effects. If true, this suggests statins may also promote immune checkpoint inhibition and increase the effects of immune checkpoint inhibitor drugs. The side effects of statins, like muscle pain, neurological symptoms, and the induction of type 2 diabetes, are not incorporated into the meta-analysis, but are addressed in the editorial. Here are the major points from each:
Meta-Analysis
The retrospective analysis asked whether concurrent use of statins with immune checkpoint inhibitors influenced the outcome in the following studies with cancer types: non-small cell lung cancer (NSCLC; n=8 studies), melanoma (n=1), pan-cancer (n=12), renal cell carcinoma (n=3), and urothelial carcinoma (n=1). Within the 25 studies, 46,154 participants were used to analyze overall survival, and 7,786 patients were used to analyze progression-free survival. Statin use ranged from 8.7% to 50.0% of the patients, who were from either Asia, Europe, or the U.S.
The results are nuanced and varied:
- In the pooled analysis, statin use was associated with a 20% reduction in mortality risk and disease progression when compared to non-statin users.
- Patients with renal cell carcinoma undergoing immune checkpoint inhibitor therapy and statin use had improved overall and progression-free survival.
- No effect on prognosis was found in patients diagnosed with NSCLC or melanoma.
- European patients using statins had better overall survival. No effects were found in patients from Asia or the U.S. using statins concurrent with immune checkpoint inhibitors.
- Patients from Asia had better progression-free survival. No effects on progression-free survival were observed in patients from Europe or the U.S. with concurrent medications.
- The meta-analysis did not establish a specific type of statin, indicate a dosage, compare timing, or verify medication adherence.
Editorial
The editorial examines whether it is time to incorporate the routine use of statins with immune checkpoint inhibitors and change practice patterns for patients undergoing treatment. Citing the study by Liao Y et al. and others, the study suggests that concurrent use of statins positively impacts patients undergoing cancer therapy with immune checkpoint inhibitors. Although there is no definitive molecular mechanism of a signaling interaction, metabolic reprogramming and/or dysfunctional carbohydrate metabolism may be reasons why statins show efficacy in patients with cancer. Here are major problems cited in the editorial with incorporating statins into routine, combination use:
- There is a lack of unanimity on whether statins are beneficial or have no impact on survival.
- Up to 40% of patients on statins exhibit poor compliance with therapeutic adherence.
- Toxicity was not included in the meta-analysis.
- About 82% of the cases (n=37,741 patients) were reported as abstracts. Approximately 40% to 70% of meeting abstracts are never published as full, peer-reviewed publications.
- More studies are needed to define the long-term implications of a combination treatment before supporting the concurrent use of statins with immune checkpoint inhibitors.
References
Liao, Y, Lin Y, Ye X et al. Concomitant Statin Use and Survival in Patients With Cancer on Immune Checkpoint Inhibitors: A Meta Analysis. JCO Oncol Pract. 2025:OP2400583. doi: 10.1200/OP-24-00583
Raghavan D and Symanowski J. Abstract Thinking and Statins With Immune Checkpoint Inhibitors: Enough to Change Clinical Practice? JCO Oncol Pract. 2025:OP2500117. doi: 10.1200/OP-25-00117.
