PMID- 24928832 OWN - NLM STAT- MEDLINE DCOM- 20150608 LR - 20240229 IS - 1569-8041 (Electronic) IS - 0923-7534 (Print) IS - 0923-7534 (Linking) VI - 25 IP - 9 DP - 2014 Sep TI - A randomized, phase II study of afatinib versus cetuximab in metastatic or recurrent squamous cell carcinoma of the head and neck. PG - 1813-1820 LID - S0923-7534(19)35105-1 [pii] LID - 10.1093/annonc/mdu216 [doi] AB - BACKGROUND: Afatinib is an oral, irreversible ErbB family blocker that has shown activity in epidermal growth factor receptor (EGFR)-mutated lung cancer. We hypothesized that the agent would have greater antitumor activity compared with cetuximab in recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients, whose disease has progressed after platinum-containing therapy. PATIENTS AND METHODS: An open-label, randomized, phase II trial was conducted in 43 centers; 124 patients were randomized (1 : 1) to either afatinib (50 mg/day) or cetuximab (250 mg/m(2)/week) until disease progression or intolerable adverse events (AEs) (stage I), with optional crossover (stage II). The primary end point was tumor shrinkage before crossover assessed by investigator (IR) and independent central review (ICR). RESULTS: A total of 121 patients were treated (61 afatinib, 60 cetuximab) and 68 crossed over to stage II (32 and 36 respectively). In stage I, mean tumor shrinkage by IR/ICR was 10.4%/16.6% with afatinib and 5.4%/10.1% with cetuximab (P = 0.46/0.30). Objective response rate was 16.1%/8.1% with afatinib and 6.5%/9.7% with cetuximab (IR/ICR). Comparable disease control rates were observed with afatinib (50%) and cetuximab (56.5%) by IR; similar results were seen by ICR. Most common grade >/=3 drug-related AEs (DRAEs) were rash/acne (18% versus 8.3%), diarrhea (14.8% versus 0%), and stomatitis/mucositis (11.5% versus 0%) with afatinib and cetuximab, respectively. Patients with DRAEs leading to treatment discontinuation were 23% with afatinib and 5% with cetuximab. In stage II, disease control rate (IR/ICR) was 38.9%/33.3% with afatinib and 18.8%/18.8% with cetuximab. CONCLUSION: Afatinib showed antitumor activity comparable to cetuximab in R/M HNSCC in this exploratory phase II trial, although more patients on afatinib discontinued treatment due to AEs. Sequential EGFR/ErbB treatment with afatinib and cetuximab provided sustained clinical benefit in patients after crossover, suggesting a lack of cross-resistance. CI - (c) The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. FAU - Seiwert, T Y AU - Seiwert TY AD - Department of Medicine, University of Chicago Medical Centre, Chicago, USA. Electronic address: tseiwert@medicine.bsd.uchicago.edu. FAU - Fayette, J AU - Fayette J AD - Department of Medicine, Universite de Lyon, Lyon. FAU - Cupissol, D AU - Cupissol D AD - Institut du Cancer de Montpellier Val d'Aurelle, Montpellier, France. FAU - Del Campo, J M AU - Del Campo JM AD - Department of Medical Oncology, Hospital Universitario Vall d'Hebron, Barcelona, Spain. FAU - Clement, P M AU - Clement PM AD - Division of Oncology, KU Leuven, Leuven, Belgium. FAU - Hitt, R AU - Hitt R AD - Centro Integral Oncologico Clara Campal (CIOCC), Madrid, Spain. FAU - Degardin, M AU - Degardin M AD - Centre Oscar Lambret, Lille, France. FAU - Zhang, W AU - Zhang W AD - Boehringer Ingelheim Shanghai Pharmaceuticals Co., Ltd, Shanghai, China. FAU - Blackman, A AU - Blackman A AD - Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, USA. FAU - Ehrnrooth, E AU - Ehrnrooth E AD - Boehringer Ingelheim Danmark A/S, Copenhagen, Denmark. FAU - Cohen, E E W AU - Cohen EEW AD - Department of Medicine, University of California San Diego Moores Cancer Center, La Jolla, USA. LA - eng PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20140613 PL - England TA - Ann Oncol JT - Annals of oncology : official journal of the European Society for Medical Oncology JID - 9007735 RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Antineoplastic Agents) RN - 0 (Quinazolines) RN - 41UD74L59M (Afatinib) RN - EC 2.7.10.1 (EGFR protein, human) RN - EC 2.7.10.1 (ERBB2 protein, human) RN - EC 2.7.10.1 (ErbB Receptors) RN - EC 2.7.10.1 (Receptor, ErbB-2) RN - PQX0D8J21J (Cetuximab) SB - IM MH - Adult MH - Afatinib MH - Aged MH - Aged, 80 and over MH - Antibodies, Monoclonal, Humanized/adverse effects/*therapeutic use MH - Antineoplastic Agents/adverse effects/*therapeutic use MH - Carcinoma, Squamous Cell/*drug therapy MH - Cetuximab MH - ErbB Receptors/antagonists & inhibitors MH - Female MH - Head and Neck Neoplasms/*drug therapy MH - Humans MH - Male MH - Middle Aged MH - Quinazolines/adverse effects/*therapeutic use MH - Receptor, ErbB-2/antagonists & inhibitors MH - Squamous Cell Carcinoma of Head and Neck MH - Treatment Outcome MH - Young Adult PMC - PMC4143093 OTO - NOTNLM OT - EGFR inhibitor therapy OT - afatinib OT - cetuximab OT - metastatic HNSCC OT - recurrent HNSCC EDAT- 2014/06/15 06:00 MHDA- 2015/06/09 06:00 PMCR- 2014/06/13 CRDT- 2014/06/15 06:00 PHST- 2014/06/15 06:00 [entrez] PHST- 2014/06/15 06:00 [pubmed] PHST- 2015/06/09 06:00 [medline] PHST- 2014/06/13 00:00 [pmc-release] AID - S0923-7534(19)35105-1 [pii] AID - mdu216 [pii] AID - 10.1093/annonc/mdu216 [doi] PST - ppublish SO - Ann Oncol. 2014 Sep;25(9):1813-1820. doi: 10.1093/annonc/mdu216. Epub 2014 Jun 13.