PMID- 23775486 OWN - NLM STAT- MEDLINE DCOM- 20140225 LR - 20181202 IS - 1097-0142 (Electronic) IS - 0008-543X (Linking) VI - 119 IP - 16 DP - 2013 Aug 15 TI - Phase 2 trial of afatinib, an ErbB family blocker, in solid tumors genetically screened for target activation. PG - 3043-51 LID - 10.1002/cncr.28120 [doi] AB - BACKGROUND: The efficacy of afatinib, an irreversible ErbB Family Blocker, was evaluated in patients who had 1 of 4 categories of solid tumors with epidermal growth factor receptor/human epidermal growth factor receptor 2 (EGFR/HER2) gene amplification or EGFR-activating mutations. METHODS: Patients with previously treated but ErbB inhibitor-naive esophagogastric, biliary tract, urothelial tract, or gynecologic cancers (lung cancers were excluded) harboring EGFR/HER2 gene amplification or high polysomy were identified by fluorescence in situ hybridization (FISH). Tumors were also screened for EGFR mutations. The primary endpoint was the objective response rate; secondary endpoints included the clinical benefit rate, pharmacokinetics, and safety. RESULTS: Of 385 prescreened patients, 38 had FISH-positive tumors (10 with EGFR amplification and 29 with HER2 amplification or high polysomy [1 tumor had EGFR/HER2 high polysomy]; none had EGFR-activating mutations), and 20 patients received treatment with afatinib 50 mg daily. The objective response rate was 5% (1 of 20 patients), and the best objective response included 1 complete response. Eight patients experienced stable disease. The most frequently reported adverse events were diarrhea, rash, and decreased appetite. The trial closed early because of slow recruitment. CONCLUSIONS: Single-agent afatinib activity was limited, yet encouraging, in selected tumors that were screened prospectively for target activation. The implementation of a biomarker-driven approach using a low-frequency biomarker for patient selection across multiple tumor types can be challenging. CI - Copyright (c) 2013 American Cancer Society. FAU - Kwak, Eunice L AU - Kwak EL AD - Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA. FAU - Shapiro, Geoffrey I AU - Shapiro GI FAU - Cohen, Seth M AU - Cohen SM FAU - Becerra, Carlos R AU - Becerra CR FAU - Lenz, Heinz-Josef AU - Lenz HJ FAU - Cheng, Wen-Fang AU - Cheng WF FAU - Su, Wu-Chou AU - Su WC FAU - Robohn, Meghan AU - Robohn M FAU - Le Maulf, Florence AU - Le Maulf F FAU - Lobmeyer, Maximilian T AU - Lobmeyer MT FAU - Chand, Vikram K AU - Chand VK FAU - Iafrate, A John AU - Iafrate AJ LA - eng PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20130614 PL - United States TA - Cancer JT - Cancer JID - 0374236 RN - 0 (Quinazolines) RN - 41UD74L59M (Afatinib) RN - EC 2.7.10.1 (ErbB Receptors) RN - EC 2.7.10.1 (Receptor, ErbB-2) SB - IM MH - Adult MH - Afatinib MH - Aged MH - Aged, 80 and over MH - ErbB Receptors/*antagonists & inhibitors/genetics/metabolism MH - Female MH - Gene Amplification MH - Humans MH - In Situ Hybridization, Fluorescence MH - Male MH - Middle Aged MH - Neoplasms/*drug therapy/enzymology/genetics MH - Prospective Studies MH - Quinazolines/pharmacokinetics/*therapeutic use MH - Receptor, ErbB-2/genetics/metabolism MH - Treatment Outcome OTO - NOTNLM OT - EGFR OT - EGFR-activating mutations OT - ErbB Family Blocker OT - HER2 OT - afatinib OT - epidermal growth factor receptor OT - gene amplification OT - human epidermal growth factor receptor 2 OT - solid tumors EDAT- 2013/06/19 06:00 MHDA- 2014/02/26 06:00 CRDT- 2013/06/19 06:00 PHST- 2013/01/17 00:00 [received] PHST- 2013/03/11 00:00 [revised] PHST- 2013/03/15 00:00 [accepted] PHST- 2013/06/19 06:00 [entrez] PHST- 2013/06/19 06:00 [pubmed] PHST- 2014/02/26 06:00 [medline] AID - 10.1002/cncr.28120 [doi] PST - ppublish SO - Cancer. 2013 Aug 15;119(16):3043-51. doi: 10.1002/cncr.28120. Epub 2013 Jun 14.