Gastric Acid suppression is associated with decreased erlotinib efficacy in non-small-cell lung cancer.

Abstract

BACKGROUND:

Erlotinib is a key therapy for advanced NSCLC. Concurrent AS therapy with TKIs might reduce TKI plasma levels. Because of gastroesophageal reflux disease prevalence, this retrospective analysis was undertaken to determine if coadministering erlotinib with AS therapy affected NSCLC outcomes.

PATIENTS AND METHODS:

Records of advanced NSCLC patients who received erlotinib from 2007 to 2012 at a large, centralized, cancer institution were retrospectively reviewed. Pertinent demographic data were collected and concomitant AS treatment was defined as AS prescription dates overlapping with ≥ 20% of erlotinib treatment duration. Records of patients who received erlotinib for ≥ 1 week were analyzed for progression-free survival (PFS) and overall survival (OS).

RESULTS:

Stage IIIB/IV NSCLC patients (n = 544) were identified and 507 had adequate data for review. The median age was 64 years and 272 were female. Adenocarcinoma (n = 318; 64%) and squamous (n = 106; 21%) were predominant subtypes; 124 patients received concomitant AS therapy. In this unselected population, median PFS and OS in AS versus no AS groups were 1.4 versus 2.3 months (P < .001) and 12.9 versus 16.8 months (P = .003), respectively. Factoring sex, subtype, and performance status in multivariate Cox proportional hazards ratios for PFS and OS between AS and no AS groups were 1.83 (95% confidence interval [CI], 1.48-2.25) and 1.37 (95% CI, 1.11-1.69), respectively.

CONCLUSION:

This large population-based study suggests erlotinib efficacy might be linked with gastric pH and OS could be adversely affected. To our knowledge, this is the first study demonstrating a possible negative clinical effect of coadministration of erlotinib with AS therapy. Further prospective investigation is warranted.

• Authors: Michael P Chu, Sunita Ghosh, Carole R Chambers, Naveen Basappa, Charles A Butts, Quincy Chu, David Fenton, Anil A Joy, Randeep Sangha, Michael Smylie, Michael B Sawyer
• Journal: Clinical lung cancer (Clin Lung Cancer) Vol. 16 Issue 1 Pg. 33-9 (Jan 2015) ISSN: 1938-0690 [Electronic] United States
• PMID: 25246385 (Publication Type: Journal Article)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Histamine H2 Antagonists
• Protein Kinase Inhibitors
• Quinazolines
• Erlotinib Hydrochloride
• Omeprazole

Topics

• Carcinoma, Non-Small-Cell Lung (complications, drug therapy, mortality)
• Drug Interactions
• Erlotinib Hydrochloride
• Female
• Gastric Acid (metabolism)
• Gastroesophageal Reflux (complications, drug therapy, mortality)
• Histamine H2 Antagonists (administration & dosage, adverse effects)
• Humans
• Lung Neoplasms (complications, drug therapy, mortality)
• Male
• Middle Aged
• Omeprazole (administration & dosage, adverse effects)
• Population Groups
• Protein Kinase Inhibitors (administration & dosage, adverse effects)
• Quinazolines (administration & dosage, adverse effects)
• Retrospective Studies
• Survival Analysis
• Treatment Outcome