Continued use of afatinib with the addition of cetuximab after progression on afatinib in patients with EGFR mutation-positive non-small-cell lung cancer and acquired resistance to gefitinib or erlotinib Journal Article


Authors: Horn, L.; Gettinger, S.; Camidge, D. R.; Smit, E. F.; Janjigian, Y. Y.; Miller, V. A.; Pao, W.; Freiwald, M.; Fan, J.; Wang, B.; Chand, V. K.; Groen, H. J. M.
Article Title: Continued use of afatinib with the addition of cetuximab after progression on afatinib in patients with EGFR mutation-positive non-small-cell lung cancer and acquired resistance to gefitinib or erlotinib
Abstract: Objectives In a phase Ib trial, afatinib plus cetuximab demonstrated promising clinical activity (objective response rate [ORR]: 29%; median progression-free survival [PFS]: 4.7 months) in patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC) with acquired resistance to erlotinib or gefitinib. Here, a separate cohort exploring afatinib plus cetuximab after progression on afatinib is reported. Materials and methods Patients with EGFR mutation-positive NSCLC who progressed on erlotinib or gefitinib received afatinib 40 mg daily until progression, followed by afatinib daily plus cetuximab 500 mg/m2 every 2 weeks until progression or intolerable adverse events (AEs). Endpoints included safety, ORR, and PFS. Results Thirty-seven patients received afatinib monotherapy. Two (5%) patients responded; median PFS was 2.7 months. Thirty-six patients transitioned to afatinib plus cetuximab. Four (11%) patients responded; median PFS was 2.9 months. Median PFS with afatinib plus cetuximab for patients who received afatinib monotherapy for ≥12 versus <12 weeks was 4.9 versus 1.8 months (p = 0.0354), and for patients with T790M-positive versus T790M-negative tumors was 4.8 versus 1.8 months (p = 0.1306). Fifty percent of patients receiving afatinib plus cetuximab experienced drug-related grade 3/4 AEs. The most frequent drug-related AEs (any grade) were diarrhea (70%), rash (49%), and fatigue (35%) with afatinib monotherapy and rash (69%), paronychia (39%), and dry skin (36%) with afatinib plus cetuximab. Conclusion Sequential EGFR blockade with afatinib followed by afatinib plus cetuximab had a predictable safety profile and demonstrated modest activity in patients with EGFR mutation-positive NSCLC with resistance to erlotinib or gefitinib. ClinicalTrials.gov identifier NCT01090011. © 2017 The Author(s)
Keywords: cetuximab; egfr; nsclc; afatinib; phase ib
Journal Title: Lung Cancer
Volume: 113
ISSN: 0169-5002
Publisher: Elsevier Ireland Ltd.  
Date Published: 2017-11-01
Start Page: 51
End Page: 58
Language: English
DOI: 10.1016/j.lungcan.2017.08.014
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 2 October 2017 -- Source: Scopus
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  1. Yelena Yuriy Janjigian
    303 Janjigian