(62) Prevalence of Use of GABA Receptor Positive Allosteric Modulator Use and Associations with Treatment Discontinuation Among Patients Receiving Cancer Immunotherapy

Publication Number: 736

Background: Gamma-amino butyric acid (GABA), the inhibitory neurotransmitter, and its receptors are known to have several critical physiological functions outside the nervous system. The expression of GABA in immune cells and the role of GABA signaling in tumorigenesis has led to increasing interest in exploring this as a potential target or mediator of response for anticancer drugs. Evidence is limited on the real-world prevalence of GABAergic medications and their impact on outcomes in patients receiving cancer immunotherapy.

Objectives: To characterize the use of GABA receptor positive allosteric modulators (benzodiazepines and zolpidem) among cancer patients undergoing immune checkpoint inhibitor therapy.

Methods: This descriptive study included patients starting immune checkpoint inhibitor therapy for lung, head and neck, liver, and renal cancer between January 2010 and June 2019 using IBM MarketScan Commercial Claims and Medicare databases. Patients were required to be continuously enrolled from 365 days prior to initiation of treatment with atezolizumab, avelumab, cemiplimab, durvalumab, ipilimumab, nivolumab or pembrolizumab and were followed until discontinuation, disenrollment or end of the study period. Baseline and concurrent use of benzodiazepines or zolpidem was identified and cumulative exposure was estimated as daily diazepam equivalent doses. Multivariable Cox proportional hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) associated with treatment discontinuation.

Results: Among 8295 patients receiving immune checkpoint inhibitor therapy included in the study, 1906 (21%) concurrently received benzodiazepines or zolpidem during follow up. Compared to patients that did not receive GABA modulators, patients receiving GABA modulators were older (median age 62 vs 59, P< 0.001) and had a higher proportion of female patients (48%) and prior use of GABA modulators at baseline (66% vs. 16%; P< 0.001). Among patients exposed to GABA modulators during follow up, 29% received 5mg or greater diazepam equivalents per day. Overall, baseline GABA modulator use was associated with lower rates of discontinuation of immunotherapy (HR 0.91, 95% CI 0.86-0.97) which varied by cancer site.

Conclusions: In this cohort of patients with commercial and Medicare insurance receiving immune checkpoint inhibitor therapy for cancer, we found a non-trivial number of patients were concurrently receiving GABA modulators and had an observed lower rate of treatment discontinuation. More investigation is required to determine the potential mediating role of GABA modulators on the etiopathogenesis of cancers treated with immunotherapy.