Phase 2 trial of afatinib, an ErbB family blocker, in solid tumors genetically screened for target activation
Journal
Cancer
Journal Volume
119
Journal Issue
16
Pages
3043-3051
Date Issued
2013
Author(s)
Kwak E.L.
Shapiro G.I.
Cohen S.M.
Becerra C.R.
Lenz H.-J.
Su W.-C.
Robohn M.
Le Maulf F.
Lobmeyer M.T.
Chand V.K.
Iafrate A.J.
Abstract
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. ? 2013 American Cancer Society.
SDGs
Other Subjects
afatinib; alkaline phosphatase; aspartate aminotransferase; creatinine; epidermal growth factor receptor; epidermal growth factor receptor 2; adult; aged; alkaline phosphatase blood level; alopecia; anemia; antineoplastic activity; article; backache; bacteremia; biliary tract cancer; cancer control; cancer growth; cancer patient; cancer screening; chemotherapy induced emesis; constipation; coughing; creatinine blood level; decreased appetite; dehydration; dermatitis; dermatitis acneiform; diarrhea; dizziness; drug blood level; drug dose reduction; drug eruption; drug safety; drug targeting; dry skin; dysgeusia; dyspepsia; dyspnea; EGFR gene; epistaxis; Escherichia coli infection; esophagus cancer; fatigue; female; female genital tract fistula; fistula; fluorescence in situ hybridization; gene activation; gene amplification; gene mutation; gene targeting; genetic screening; gynecologic cancer; hematuria; HER2 gene; human; hyperbilirubinemia; hypokalemia; hypomagnesemia; hyponatremia; hypotension; insomnia; major clinical study; male; monotherapy; multicenter study; multiple cycle treatment; muscle spasm; musculoskeletal pain; nausea; open study; paronychia; pelvis pain syndrome; peripheral edema; phase 2 clinical trial; pleura effusion; polysome; priority journal; protein family; pruritus; rhinorrhea; side effect; solid tumor; stomach cancer; stomatitis; thorax pain; treatment response; urinary tract infection; urogenital tract cancer; weight reduction
Type
journal article