Presented at the 2011 European Multidisciplinary Cancer Conference; September 23–27, 2011; Stockholm, Sweden.
Phase 2 trial of afatinib, an ErbB family blocker, in solid tumors genetically screened for target activation
Version of Record online: 14 JUN 2013
Copyright © 2013 American Cancer Society
Volume 119, Issue 16, pages 3043–3051, 15 August 2013
How to Cite
Kwak, E. L., Shapiro, G. I., Cohen, S. M., Becerra, C. R., Lenz, H.-J., Cheng, W.-F., Su, W.-C., Robohn, M., Le Maulf, F., Lobmeyer, M. T., Chand, V. K. and Iafrate, A. J. (2013), Phase 2 trial of afatinib, an ErbB family blocker, in solid tumors genetically screened for target activation. Cancer, 119: 3043–3051. doi: 10.1002/cncr.28120
ELK, VKC and AJI contributed to concept and design. ELK, H-JL, W-FC, W-CS, MR, FLM, MTL, VKC and AJI were involved in the collection and assembly of data. ELK, H-JL, W-FC, MR, FLM, MTL, VKC and AJI contributed to data analysis and interpretation. ELK, GIS, H-JL, MR, FLM, MTL, VKC and AJI were involved in manuscript writing. ELK, GIS, SMC, H-JL, CRB, W-FC, W-CS, MR, FLM, MTL, VKC and AJI gave final approval of manuscript. ELK, GIS, SMC, CRB, H-JL, and W-FC contributed to the provision of study materials or patients.
- Issue online: 2 AUG 2013
- Version of Record online: 14 JUN 2013
- Manuscript Accepted: 15 MAR 2013
- Manuscript Revised: 11 MAR 2013
- Manuscript Received: 17 JAN 2013
- epidermal growth factor receptor;
- EGFR-activating mutations;
- ErbB Family Blocker;
- gene amplification;
- human epidermal growth factor receptor 2;
- solid tumors
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.
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.
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.
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. Cancer 2013;119:3043—3051. © 2013 American Cancer Society.