ANN ARBOR, MI — Can commonly prescribed medications influence immune checkpoint inhibitor (ICI outcomes) in nonsmall cell lung cancer (NSCLC)?
A new study used a national patient sample and a negative control cohort from the VHA to seek an answer to that question.
Researchers from the University of Michigan and the VA Ann Arbor, MI, Healthcare System noted that medications such as proton pump inhibitors (PPIs), antihistamines and nonsteroidal anti-inflammatory drugs have been linked to ICI efficacy in patients but suggested that those associations might reflect unmeasured confounding instead of true pharmacologic effects. The findings were published in the journal Cancer.1
To find out, the authors identified 3,739 VHA patients with Stage IV NSCLC treated with first- or second-line ICI therapy, as well as another 6,585, treated with from 2005 to 2023. The study team assessed the baseline use of 20 common medication classes and an immunomodulatory drug score. For any medication with a nominally significant association (p < 0.05), the same analysis was repeated in the chemotherapy group to test for nonspecific effects.
After propensity weighting, their results indicated that 14 of 20 medication classes showed no association with overall survival or the time to time to next treatment, or TTNT, in the ICI cohort. The researchers determined that lLoop diuretics, anticoagulants, opioids, penicillin antibiotics and fluoroquinolone antibiotics were associated with worse outcomes, with similar effects identified in the chemotherapy group. “A higher immunomodulatory drug score also was associated with inferior outcomes among ICI patients, but this association was likewise present in the chemotherapy cohort,” they explained.
The authors concluded that commonly prescribed medications did not appear to alter ICI efficacy in stage IV NSCLC, suggesting, “Prior associations reported in the literature may be attributable to unmeasured confounding rather than true drug-immunotherapy interactions.”
Brinzevich D, Falvello V, Rehmani SS, Strohbehn GW, Ramnath N, Dykstra MP, Higgins LM, Elliott D, Schipper MJ, Green MD, Bryant AK. The effect of common medications on the efficacy of immune checkpoint inhibitors. Cancer. 2025 Dec 15;131(24):e70222. doi: 10.1002/cncr.70222. PMID: 41390939; PMCID: PMC12701955.