The Predictive Value of Gastrin for the Absorption of Erlotinib in Patients with Non-Small Cell Lung Cancer

Gastrin regulates gastric acid secretion and increases when gastric acidity is reduced. Erlotinib, a small-molecule inhibitor used to treat patients with advanced non-small cell lung cancer (NSCLC), has a pH-dependent absorption. We therefore investigated whether elevated gastrin levels, for example, due to proton pump inhibitor (PPI) use or achlorhydria, are associated with reduced erlotinib absorption. Data of patients treated with erlotinib for NSCLC that were included in two previously conducted pharmacokinetic studies were used for this pharmacological proof-of-principle analysis. In these studies, patients were randomized to PPI use or not. Gastrin levels were quantified in samples drawn just before intake of erlotinib and used to study correlations with erlotinib concentrations. The pharmacokinetic endpoints area under the curve (AUC), trough concentration, and maximum concentration ( C max ) were correlated to gastrin concentrations and compared in patients with and without hypergastrinemia (gastrin ≥ 150 pg/mL). A total of 52 patients on erlotinib were included. Gastrin showed a significant inverse correlation with erlotinib AUC 0–12h ( r = −0.277; p = 0.047) and C max ( r = −0.423; p = 0.002). In 11 patients with hypergastrinemia (gastrin ≥ 150 pg/mL), median erlotinib C max was > 30% lower (1890 ng/mL vs 1200 ng/mL; p = 0.024). The median AUC 0–12h and AUC 0–24h of erlotinib showed a non-significant trend towards lower AUCs of, respectively, 29% ( p = 0.087) and 23% ( p = 0.074), in patients with hypergastrinemia. Gastrin concentrations could potentially serve as a marker for erlotinib absorption, helping identify patients at risk for low erlotinib exposure.