The concomitant use of proton pump inhibitors and BRAF/MEK inhibitors in metastatic melanoma

Background: Proton-pump inhibitors (PPIs) are commonly used by patients with cancer, although they could reduce the absorption of oral anticancer targeted therapies. The US Food and Drug Administration states that the effect of PPIs on the efficacy of dabrafenib use by patients with metastatic melanoma is unknown. As a precautionary measure, the European Society for Medical Oncology recommends avoiding PPIs for patients receiving dabrafenib.

Objectives: To determine the effect of the concomitant use of PPIs and BRAF/MEK inhibitors in patients with metastatic melanoma.

Methods: Patients with advanced melanoma receiving BRAF/MEK inhibitors as first-line treatments between 2015 and 2017 in France were selected using the French National Health Insurance database. We compared time-to-treatment discontinuation (TTD) and overall survival (OS) according to concomitant PPI exposure. We balanced the baseline characteristics of patients exposed and nonexposed to PPIs using an overlap weighting method based on a propensity score.

Results: The metastatic melanoma cohort comprised 1028 patients receiving BRAF/MEK inhibitors, including 361 (35.1%) patients using PPIs. PPI users had more comorbidities and a more severe metastatic disease. After having equally distributed metastatic sites and comorbidities across patients exposed and nonexposed to PPIs, concomitant PPI use was not associated with shorter TTD [weighted hazard ratio (wHR) 1.03, 95% confidence interval (CI) 0.86-1.24] or OS (wHR 1.11, 95% CI 0.88-1.39). Consistent results were observed when restricting the population to patients receiving dabrafenib, or when narrowing exposure to PPIs with stronger inhibition of cytochromes.

Conclusions: In a population-based cohort of patients with advanced melanoma, the concomitant use of PPIs and BRAF/MEK inhibitors was not associated with worse outcome.