Author of

• 11745

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  P2.11 - Poster Session 2 - NSCLC Novel Therapies (ID 209)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Medical Oncology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/29/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 11787

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    P2.11-042 - Acid suppression therapy impairs Erlotinib efficacy in Non-Small Cell Lung Cancer (ID 2930)

    09:30 - 09:30  |  Author(s): M. Smylie
    • Abstract

    Background
    Erlotinib is a key treatment option in all advanced or metastatic non-small cell lung cancer (mNSCLC) subtypes regardless of epidermal growth factor receptor (EGFR) status. Despite side effect advantages over cytotoxic chemotherapy, a shortcoming of erlotinib is pH-dependent absorption. Recent evidence highlights this inconsistency further by showing reduced plasma levels of various oral tyrosine kinase inhibitors (TKIs) in the presence of acid suppression therapy. Given the prevalence of gastroesophageal reflux disease (GERD) and diseases that use acid suppression, goals of this study are to determine if coadministration of acid suppressants and erlotinib affected clinical outcomes in advanced NSCLC patients.

    Methods
    A cohort of patients with mNSCLC from 2007-2012 who received erlotinib through our institution was retrospectively reviewed. In addition to stage, age, gender, performance status, and NSCLC subtype, patients were then identified as receiving acid suppression (AS) if their pharmacy records included either proton pump inhibitors (PPIs) or histamine blockers (anti-H2). Patients were considered taking these medications concomitantly if dates for acid suppressants overlapped their erlotinib prescription by ≥ 20% of the treatment duration. Patients who received erlotinib for ≥ 1 week were analyzed for progression free survival (PFS) and overall survival (OS).

    Results
    544 stage IIIB/IV NSCLC patients were identified. Of those, 507 were eligible for review. Median age was 64 years, gender 235 male, and 272 female. By subtype, 318 were adenocarcinoma, 106 squamous, 43 poorly differentiated, 11 large cell, and 29 not otherwise specified (NOS). 124 patients received concomitant AS therapy with the most common type being PPIs. Analysis unselected for EGFR mutational status yielded median PFS and OS in the AS versus no-AS group as 1.4 v 2.3 months (p<0.001) and 12.9 v 16.8 months (p=0.003), respectively. In multivariate analysis with gender, NSCLC subtype, and performance status, Cox proportional hazards ratios for PFS and OS for AS and non-AS groups were 1.83 (95% CI 1.48-2.25) and 1.37 (95% CI 1.11-1.69) respectively. Subgroup analysis by subtype in the AS and non-AS groups was significant in the following types (p<0.05): adenocarcinoma, PFS 1.8 v 2.7 months, OS 13.2 v 17.5 months; squamous PFS 1.5 v 2.3 months, OS 13.4 v 15.9 months; poorly differentiated PFS 0.8 v 2.0 months, OS 7.6 v 15.5 months, and NOS PFS 1.2 v 1.7 months, OS 10.8 v 14.5 months. Effects of AS in EGFR mutated patients are being studied.

    Conclusion
    Despite limitations of retrospective analyses, this large population based study demonstrates erlotinib efficacy is dependent on gastric acidity and OS can be adversely affected. This is the first study the authors are aware of that demonstrates an impact on clinical outcomes by co-administration of acid suppression and TKI therapy. Caution should be taken with co-administration of other TKIs and acid suppressive therapy.