Is Immunotherapy With Concomitant Proton Pump Inhibitor Use a Viable Combination?
Menée au Japon à partir de données de 13 hôpitaux portant sur 425 patients atteints d'un cancer du poumon non à petites cellules (durée médiane de suivi : 18,5 mois), cette étude multicentrique évalue, en fonction du traitement reçu (pembrolizumab en monothérapie ou inhibiteur de point de contrôle immunitaire en combinaison avec une chimiothérapie), l'association entre l'utilisation concomitante d'un inhibiteur de pompe à protons et la survie des patients
Lung cancer is the second most common cancer diagnosed worldwide and the first most common cause of cancer-related deaths in both men and women. Although the introduction of immunotherapy with immune checkpoint inhibitors (ICIs) offered new hopes for patients with advanced non–small cell lung cancer (NSCLC), almost doubling 5-year overall survival (OS) with respect to chemotherapy, there is still an unmet need for optimizing outcomes, especially among nonresponders, who represent approximately one-third of patients.In recent years, several retrospective studies have suggested that there may be a potential interference of concomitant medications, such as steroids, antibiotics, and proton pump inhibitors (PPIs), with immunotherapy outcomes. Particularly, a history of PPI administration at the beginning of treatment or during treatment has been associated with worse outcomes in patients receiving ICIs, especially anti-PD-L1 (programmed cell death 1 ligand 1) agents. PPI might change the composition of the gut microbiome due to the downstream translocation of oral commensals, thus altering its immunomodulating properties and impairing ICI activity. In fact, as recently demonstrated by Derosa et al, a precise equilibrium of symbiotic bacteria with the right relative abundance of Akkermansia muciniphila (ie, <4.799%), is more associated with ICI outcomes in patients with NSCLC than PD-L1 levels, although the type of bacteria might play a role as well. Some of these studies provided conflicting results or remained inconclusive due to their small sample size and retrospective nature, although a recent large meta-analysis by Lopes et al conducted of 20 042 patients with different tumors treated with ICIs concluded that progression-free survival (PFS) (hazard ratio [HR], 1.28; 95% CI, 1.15–1.42) and OS (HR, 1.37; 95% CI, 1.23–1.52) were negatively associated with PPI. Nevertheless, whether PPIs are associated with immunotherapy response is still to be prospectively determined.