1470P - Statin use and overall mortality in patients with advanced non-small cell lung cancer receiving anti-PD(L)1 immunotherapy: A SEER Medicare database analysis

Background

Statins, commonly used to lower cholesterol, are inhibitors of Yes-associated protein (YAP), a transcription co-activator mediating cell survival and anti-tumor immunity. Concurrent statin with anti-PD1 immune checkpoint blockade (ICB) has shown preclinical synergy, and studies suggest improved survival among ICB-treated patients (pts) with non-small cell lung cancer (NSCLC) who take statins. We used the United States Surveillance Epidemiology and End Results (SEER) Medicare-linked database to assess overall mortality in a real-world population of pts with NSCLC receiving anti-PD(L)1 ICB and concurrent statin.

Methods

Pts in SEER (≥65 years old) diagnosed with NSCLC in 2007–2017 and treated with anti-PD(L)1 ICB were included. ICB and statin therapy status were ascertained from Medicare claims. Pts were followed from date of first ICB claim until date of death, 4 weeks from last ICB claim, or 12/31/2018 (database cutoff), whichever came first. Hazard ratios (HR) were estimated using Cox regression models adjusted for propensity score, NCI comorbidity Index, and demographics to determine the association between time-updated statin use and overall mortality.

Results

1401 pts were included, with 142 total deaths attained over 8710 person-months. 662 pts were statin-users and 739 were non-users. Statin users were more likely to be men compared to non-users (55% vs 43%). Median duration of anti-PD(L)1 ICB claim was similar for statin users and non-users (4.1 vs 4.2 months, respectively). Concurrent statin was associated with a 38% lower overall mortality (HR 0.62, 95% CI 0.41-0.94) compared to no statin. When extending follow-up beyond cessation of ICB claim, benefit was attenuated (HR 0.9, 95% CI 0.78-1.05). Subgroup data showed similar trends in overall mortality benefit when restricting to anti-PD-1 ICB (HR 0.63, 95% CI 0.42-0.93), as well as to simvastatin (HR 0.59, 95% CI 0.32-1.07) and atorvastatin (HR 0.67, 95% CI 0.42-1.07).

Conclusions

Concurrent statin use was associated with decreased overall mortality in a real-world population of pts with advanced NSCLC treated with anti-PD(L)1 ICB. Analyses from this dataset focused on lung-cancer specific mortality are ongoing.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

US National Institutes of Health, US National Cancer Institute.

Disclosure

J. Reuss: Financial Interests, Personal, Advisory Board: Genentech/Roche, Sanofi/Genzyme, Personalis, Guardant, AstraZeneca, Bristol Myers Squibb, Arcus, AbbVie; Financial Interests, Personal, Other, honoraria: AstraZeneca, Merck; Financial Interests, Institutional, Research Grant: Genentech/Roche; Financial Interests, Institutional, Local PI: Verastem, Nuvalent. J.R. Brahmer: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bristol Myers Squibb, Genentech/Roche, Eli Lilly, GSK, Merck, Sanofi, Regeneron; Financial Interests, Personal, Other, consulting agreement: Janssen, Johnson & Johnson; Financial Interests, Institutional, Research Funding: AstraZeneca, Bristol Myers Squibb. All other authors have declared no conflicts of interest.