PMID- 29110849 OWN - NLM STAT- MEDLINE DCOM- 20180625 LR - 20181202 IS - 1872-8332 (Electronic) IS - 0169-5002 (Linking) VI - 113 DP - 2017 Nov TI - 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. PG - 51-58 LID - S0169-5002(17)30487-7 [pii] LID - 10.1016/j.lungcan.2017.08.014 [doi] AB - 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 40mg daily until progression, followed by afatinib daily plus cetuximab 500mg/m(2) 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. CI - Copyright (c) 2017 The Author(s). Published by Elsevier B.V. All rights reserved. FAU - Horn, Leora AU - Horn L AD - Vanderbilt-Ingram Cancer Center, 777 Preston Research Building, Nashville, TN, USA. Electronic address: leora.horn@vanderbilt.edu. FAU - Gettinger, Scott AU - Gettinger S AD - Yale University School of Medicine and Yale Cancer Center, 333 Cedar Street, FMP 127, New Haven, CT, USA. Electronic address: scott.gettinger@yale.edu. FAU - Camidge, D Ross AU - Camidge DR AD - University of Colorado Cancer Center, 12801 E. 17th Avenue, Aurora, CO, USA. Electronic address: ross.camidge@ucdenver.edu. FAU - Smit, Egbert F AU - Smit EF AD - Vrije Universiteit VU Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands. Electronic address: EF.Smit@vumc.nl. FAU - Janjigian, Yelena Y AU - Janjigian YY AD - Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, 300 E66th Street, Room 1033, New York, NY, USA. Electronic address: janjigiy@mskcc.org. FAU - Miller, Vincent A AU - Miller VA AD - Foundation Medicine, Inc., 150 Second Street, Cambridge, MA, USA. Electronic address: vmiller@foundationmedicine.com. FAU - Pao, William AU - Pao W AD - Vanderbilt-Ingram Cancer Center, 777 Preston Research Building, Nashville, TN, USA. Electronic address: william.pao@vanderbilt.edu. FAU - Freiwald, Matthias AU - Freiwald M AD - Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Strasse 65, Biberach, Germany. Electronic address: matthias.freiwald@boehringer-ingelheim.com. FAU - Fan, Jean AU - Fan J AD - Boehringer Ingelheim Pharmaceuticals Inc., 900 Ridgebury Road, Ridgefield, CT, USA. Electronic address: jean.fan@boehringer-ingelheim.com. FAU - Wang, Bushi AU - Wang B AD - Boehringer Ingelheim Pharmaceuticals Inc., 900 Ridgebury Road, Ridgefield, CT, USA. Electronic address: bushi.wang@boehringer-ingelheim.com. FAU - Chand, Vikram K AU - Chand VK AD - Boehringer Ingelheim Pharmaceuticals Inc., 900 Ridgebury Road, Ridgefield, CT, USA. Electronic address: vikramkchand@gmail.com. FAU - Groen, Harry J M AU - Groen HJM AD - University of Groningen and University Medical Center Groningen, Hanzeplein 1, Groningen, The Netherlands. Electronic address: h.j.m.groen@umcg.nl. LA - eng SI - ClinicalTrials.gov/NCT01090011 PT - Clinical Trial, Phase I PT - Journal Article DEP - 20170831 PL - Ireland TA - Lung Cancer JT - Lung cancer (Amsterdam, Netherlands) JID - 8800805 RN - 0 (Quinazolines) RN - 41UD74L59M (Afatinib) RN - DA87705X9K (Erlotinib Hydrochloride) RN - EC 2.7.10.1 (EGFR protein, human) RN - EC 2.7.10.1 (ErbB Receptors) RN - PQX0D8J21J (Cetuximab) RN - S65743JHBS (Gefitinib) SB - IM MH - Adult MH - Afatinib MH - Aged MH - Aged, 80 and over MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects/pharmacokinetics/*therapeutic use MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/genetics/pathology MH - Cetuximab/administration & dosage/adverse effects MH - Cohort Studies MH - Diarrhea/chemically induced MH - Disease Progression MH - Drug Resistance, Neoplasm/*genetics MH - ErbB Receptors/*genetics MH - Erlotinib Hydrochloride/administration & dosage/adverse effects MH - Exanthema/chemically induced MH - Female MH - Gefitinib MH - Humans MH - Kaplan-Meier Estimate MH - Lung Neoplasms/*drug therapy/genetics/pathology MH - Male MH - Middle Aged MH - *Mutation MH - Quinazolines/administration & dosage/adverse effects OTO - NOTNLM OT - Afatinib OT - Cetuximab OT - EGFR OT - NSCLC OT - Phase Ib EDAT- 2017/11/08 06:00 MHDA- 2018/06/26 06:00 CRDT- 2017/11/08 06:00 PHST- 2017/03/01 00:00 [received] PHST- 2017/06/30 00:00 [revised] PHST- 2017/08/15 00:00 [accepted] PHST- 2017/11/08 06:00 [entrez] PHST- 2017/11/08 06:00 [pubmed] PHST- 2018/06/26 06:00 [medline] AID - S0169-5002(17)30487-7 [pii] AID - 10.1016/j.lungcan.2017.08.014 [doi] PST - ppublish SO - Lung Cancer. 2017 Nov;113:51-58. doi: 10.1016/j.lungcan.2017.08.014. Epub 2017 Aug 31.