• Leora Horn, Scott Gettinger, D Ross Camidge, Egbert F Smit, Yelena Y Janjigian, Vincent A Miller, William Pao, Matthias Freiwald, Jean Fan, Bushi Wang, Vikram K Chand, and GroenHarry J MHJMUniversity of Groningen and University Medical Center Groningen, Hanzeplein 1, Groningen, The Netherlands. Electronic address: h.j.m.groen@umcg.nl..
• Vanderbilt-Ingram Cancer Center, 777 Preston Research Building, Nashville, TN, USA. Electronic address: leora.horn@vanderbilt.edu.
• Lung Cancer. 2017 Nov 1; 113: 51-58.

ObjectivesIn 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 MethodsPatients with EGFR mutation-positive NSCLC who progressed on erlotinib or gefitinib received afatinib 40mg daily until progression, followed by afatinib daily plus cetuximab 500mg/m2 every 2 weeks until progression or intolerable adverse events (AEs). Endpoints included safety, ORR, and PFS.ResultsThirty-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.ConclusionSequential 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 IdentifierNCT01090011.Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

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