Proton pump inhibitors (PPIs) may reduce the efficacy of atezolizumab in patients with non-small cell lung cancer (NSCLC), according to research published in the British Journal of Cancer.
PPI use was associated with worse progression-free survival (PFS) and overall survival (OS) in patients treated with atezolizumab plus chemotherapy but not in patients who received chemotherapy alone.
Researchers uncovered these findings in a post hoc analysis of the IMpower150 trial (ClinicalTrials.gov Identifier: NCT02366143). The analysis included 1202 patients with metastatic non-squamous NSCLC who were previously chemotherapy-naïve.
The patients were randomly assigned to 1 of 3 regimens:
- Atezolizumab plus carboplatin and paclitaxel (ACP, n=402)
- Atezolizumab plus bevacizumab, carboplatin, and paclitaxel (ABCP, n=400)
- Bevacizumab plus carboplatin and paclitaxel (BCP, n=400).
Overall, there were 441 patients who received a PPI within 30 days before and 30 days after the start of study treatment. This included 139 patients in the ABCP arm, 151 in the ACP arm, and 151 in the BCP arm (P =.61).
In the BCP arm, there was no significant association between PPI use and OS (hazard ratio [HR], 1.01; 95% CI, 0.73-1.39; P =.969) or PFS (HR, 0.97; 95% CI, 0.76-1.25; P =.827).
In the ACP arm, PPI use was significantly associated with worse OS (HR, 1.45; 95% CI, 1.03-2.04; P =.033) and PFS (HR, 1.38; 95% CI, 1.07-1.78, P =.014).
In the ABCP arm, PPI use was significantly associated with worse OS (HR, 1.58; 95% CI, 1.10-2.26; P =.013) but not PFS (HR, 1.21; 95% CI, 0.92-1.60, P =.173).
When the ACP and ABCP arms were pooled together, PPI use was significantly associated with worse OS (HR, 1.53; 95% CI, 1.21-1.95; P <.001) and PFS (HR, 1.34; 95% CI, 1.12-1.61, P =.002).
“For the first time, in a cohort of patients with chemotherapy-naive, metastatic non-squamous NSCLC, PPI use has been demonstrated as an independent prognostic factor of worse survival outcomes when treated with ACP (±bevacizumab) therapy, which was not observed with BCP therapy,” the researchers wrote.
“With up to 30% of cancer patients using PPIs, often for extended periods or seemingly from a perspective that there will be no harm, the present study exemplifies an urgent need to conclusively determine if PPIs influence ICI [immune checkpoint inhibitor] efficacy and for oncologists to consider whether a PPI is critically necessary for an individual,” they concluded.
Disclosures: The IMpower150 trial was sponsored by Hoffmann-La Roche. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Hopkins AM, Kichenadasse G, McKinnon RA, et al. Efficacy of first-line atezolizumab combination therapy in patients with non-small cell lung cancer receiving proton pump inhibitors: Post hoc analysis of IMpower150. Br J Cancer. Published online October 28, 2021. doi:10.1038/s41416-021-01606-4