Kentaro Sawada1, Yoshiaki Nakamura1, Takeharu Yamanaka2, Yasutoshi Kuboki1, Daisuke Yamaguchi3, Satoshi Yuki4, Takayuki Yoshino1, Yoshito Komatsu5, Naoya Sakamoto4, Wataru Okamoto6, Satoshi Fujii7. 1. Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan. 2. Department of Biostatistics, Yokohama City University, Yokohama, Kanagawa, Japan. 3. Department of Gastroenterology, Kyoto Katsura Hospital, Kyoto, Japan. 4. Department of Gastroenterology and Hepatology, Hokkaido University Hospital, Sapporo, Hokkaido, Japan. 5. Cancer Center, Hokkaido University Hospital, Sapporo, Hokkaido, Japan. 6. Clinical Research Support Office, National Cancer Center Hospital East, Kashiwa, Chiba, Japan. 7. Division of Pathology, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, Japan. Electronic address: sfujii@east.ncc.go.jp.
Abstract
PURPOSE: To evaluate a prognostic and predictive value of HER2 amplification in patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: Patients with mCRC who underwent surgical resection of the primary tumor and who received best supportive care with or without palliative chemotherapy between 2005 and 2015 were included. HER2 immunohistochemistry was performed using formalin-fixed, paraffin-embedded primary tumor specimens. HER2 amplification was confirmed by fluorescence in-situ hybridization. The RAS and BRAFV600E mutations were centrally assessed using a PCR-based method. Patients were divided into 4 subgroups: R (RAS mutant), B (BRAFV600E mutant), H (wild-type RAS/BRAF with HER2 amplification), and W (wild-type RAS/BRAF without HER2 amplification). Overall survival (OS) and progression-free survival of anti-epidermal growth factor receptor (EGFR) therapy were assessed. RESULTS: Among 370 eligible patients, data of 359 were successfully analyzed. Fifteen tumors harbored HER2 amplifications, including 4 tumors with concomitant RAS mutation (group R). The number of patients in groups R, B, H, and W was 204, 13, 11, and 131, respectively. The median OS was 27.4 months, and the median follow-up time was 63.2 months. The median OS for groups R, B, H, and W was 24.0, 14.2, 19.9, and 39.1 months, respectively. The number of patients who received anti-EGFR therapy in groups R, B, H, and W was 17, 4, 5, and 49, respectively. Progression-free survival of anti-EGFR therapy was significantly shorter in groups R, B, and H than in group W. CONCLUSION: HER2 amplification was predictive of anti-EGFR therapy response and appeared to be prognostic in mCRC patients.
PURPOSE: To evaluate a prognostic and predictive value of HER2 amplification in patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: Patients with mCRC who underwent surgical resection of the primary tumor and who received best supportive care with or without palliative chemotherapy between 2005 and 2015 were included. HER2 immunohistochemistry was performed using formalin-fixed, paraffin-embedded primary tumor specimens. HER2 amplification was confirmed by fluorescence in-situ hybridization. The RAS and BRAFV600E mutations were centrally assessed using a PCR-based method. Patients were divided into 4 subgroups: R (RAS mutant), B (BRAFV600E mutant), H (wild-type RAS/BRAF with HER2 amplification), and W (wild-type RAS/BRAF without HER2 amplification). Overall survival (OS) and progression-free survival of anti-epidermal growth factor receptor (EGFR) therapy were assessed. RESULTS: Among 370 eligible patients, data of 359 were successfully analyzed. Fifteen tumors harbored HER2 amplifications, including 4 tumors with concomitant RAS mutation (group R). The number of patients in groups R, B, H, and W was 204, 13, 11, and 131, respectively. The median OS was 27.4 months, and the median follow-up time was 63.2 months. The median OS for groups R, B, H, and W was 24.0, 14.2, 19.9, and 39.1 months, respectively. The number of patients who received anti-EGFR therapy in groups R, B, H, and W was 17, 4, 5, and 49, respectively. Progression-free survival of anti-EGFR therapy was significantly shorter in groups R, B, and H than in group W. CONCLUSION:HER2 amplification was predictive of anti-EGFR therapy response and appeared to be prognostic in mCRC patients.