ATLANTA — Preclinical data has suggested antifungal azole derivatives have antitumor efficacy that might modulate response to immune checkpoint inhibitors (ICIs). A new study evaluated the association of azole drugs with overall survival (OS) in a population of patients with non-small cell lung cancer (NSCLC) treated with ICI within the VHA.
In the retrospective study led by researchers from Emory University and the Atlanta VA Healthcare System, the VA Corporate Data Warehouse was queried for patients diagnosed with NSCLC and treated with ICI from 2010 to 2018.
For purposes of the study, concomitant oral azole use was defined as dispensation by a VA pharmacy within 90 days of the first ICI infusion. Excluded were patients who received azole after 30 days from the analysis to mitigate immortal time bias. Overall survival was measured from the start of ICI, while Cox regression and propensity score matching were used to adjust for confounders.
The researchers identified 3,413 patients with NSCLC receiving ICI; of those, 324 (9.5%) were exposed to concomitant azoles, according to the report in the Oncologist journal. 1
As a group, azole use was not associated with OS (hazard ratio [HR] = 0.96; 95% CI, 0.84-1.09; P = 0.51), according to the results. “After stratification by azole type, clotrimazole had an association with better OS on univariable (HR = 0.75; 95% CI, 0.59-0.96; P = 0.024) and multivariable analysis (HR = 0.71; 95% CI, 0.56-0.91; P = 0.007),” the authors wrote. Propensity score matching of patients who received clotrimazole vs. no azole yielded 101 patients per matched cohort. Clotrimazole was associated with improved OS, although this did not meet the threshold for statistical significance (HR = 0.74; 0.54-1.01; P = 0.058).
“This observational study demonstrated an association between clotrimazole and OS among patients with advanced NSCLC receiving ICI,” according to the researchers. “These findings build upon preclinical evidence and support further investigation into the potential for clotrimazole as a repurposed FDA drug to improve cancer outcomes.”
- Sebastian NT, Stokes WA, Behera M, Jiang R, et. Al. The association of azole antifungals with overall survival in patients with non-small cell lung cancer receiving immune checkpoint inhibitors. Oncologist. 2024 Sep 25:oyae262. doi: 10.1093/oncolo/oyae262. Epub ahead of print. PMID: 39321212.
