Phase 2 trial of afatinib, an ErbB family blocker, in solid tumors genetically screened for target activation. Issue 16 (14th June 2013)

• Record Type: Journal Article
• Authors: Kwak, Eunice L.; Shapiro, Geoffrey I.; Cohen, Seth M.; Becerra, Carlos R.; Lenz, Heinz‐Josef; Cheng, Wen‐Fang; Su, Wu-Chou; Robohn, Meghan; Le Maulf, Florence; Lobmeyer, Maximilian T.; Chand, Vikram K.; Iafrate, A. John
• Is Part Of: Cancer. Volume 119:Issue 16(2013)
• Page Start: 3043
• Page End: 3051
• Publication Date: 2013-06-14
• Subjects: Cancer -- Periodicals; Cancer -- Cytopathology -- Periodicals; 616.99405
• DOI: 10.1002/cncr.28120
• Languages: English
• ISSNs: 0008-543X

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="cncr28120-sec-0001" sec-type="section"> <title>BACKGROUND</title> <p>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 (<italic>EGFR/HER2</italic>) gene amplification or <italic>EGFR</italic>‐activating mutations.</p> </sec> <sec id="cncr28120-sec-0002" sec-type="section"> <title>METHODS</title> <p>Patients with previously treated but ErbB inhibitor‐naive esophagogastric, biliary tract, urothelial tract, or gynecologic cancers (lung cancers were excluded) harboring <italic>EGFR/HER2</italic> gene amplification or high polysomy were identified by fluorescence in situ hybridization (FISH). Tumors were also screened for <italic>EGFR</italic> mutations. The primary endpoint was the objective response rate; secondary endpoints included the clinical benefit rate, pharmacokinetics, and safety.</p> </sec> <sec id="cncr28120-sec-0003" sec-type="section"> <title>RESULTS</title> <p>Of 385 prescreened patients, 38 had FISH‐positive tumors (10 with <italic>EGFR</italic> amplification and 29 with <italic>HER2</italic> amplification or high polysomy [1 tumor had <italic>EGFR/HER2</italic> high polysomy]; none had <italic>EGFR</italic>‐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.</p> </sec> <sec id="cncr28120-sec-0004" sec-type="section"> <title>CONCLUSIONS</title> <p>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. <bold><italic>Cancer</italic> 2013;119:3043—3051</bold>. © <italic>2013 American Cancer Society</italic>.</p> </sec> </abstract>