Meeting
2023 ASCO Breakthrough
First-line (1L) panitumumab (PAN) vs bevacizumab (BEV) in patients (pts) with HER2 amplification (HER2amp+), RAS wild type (WT) metastatic colorectal cancer (mCRC) according to tumor sidedness.
Authors
Eiji Oki
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Eiji Oki , Kei Muro , Jun Watanabe , Kohei Shitara , Kentaro Yamazaki , Hisatsugu Ohori , Manabu Shiozawa , Hirofumi Yasui , Takeo Sato , Takeshi Naito , Yoshito Komatsu , Takeshi Kato , Junpei Soeda , Kouji Yamamoto , Riu Yamashita , Kiwamu Akagi , Atsushi Ochiai , Hiroyuki Uetake , Katsuya Tsuchihara , Takayuki Yoshino
Organizations
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan, Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan, Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan, Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, Japan, Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan, Division of Medical Oncology, Japanese Red Cross Ishinomaki Hospital, Miyagi, Japan, Division of Gastrointestinal Surgery, Kanagawa Cancer Center, Kanagawa, Japan, Research and Development Center for Medical Education, Department of Clinical Skills Education, Kitasato University School of Medicine, Sagamihara, Japan, Department of Lower Gastrointestinal Surgery, Kitasato University School of Medicine, Sagamihara, Japan, Division of Cancer Chemotherapy, Hokkaido University Hospital Cancer Center, Sapporo, Japan, Department of Surgery, National Hospital Organization Osaka National Hospital, Osaka, Japan, Japan Medical Affairs, Japan Oncology Business Unit, Takeda Pharmaceutical Company Ltd., Tokyo, Japan, Department of Biostatistics, Yokohama City University School of Medicine, Yokohama, Japan, Division of Translational Informatics, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Chiba, Japan, Division of Molecular Diagnosis and Cancer Prevention, Saitama Cancer Center, Saitama, Japan, Research Institute for Biomedical Sciences, Tokyo University of Science, Tokyo, Japan, National Hospital Organization, Disaster Medical Center, Tokyo, Japan, Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan
Research Funding
Pharmaceutical/Biotech Company
Takeda Pharmaceutical Company Ltd., Tokyo, Japan
Background: HER2 gene alterations occur in 3%–5% of pts with mCRC and may be associated with aggressive tumor behavior. Gene amplification is a frequent HER2 alteration in mCRC, often leading to HER2 protein overexpression. Preclinical and retrospective studies suggest HER2 alterations may predict anti–epidermal growth factor receptor (EGFR) therapy resistance in mCRC; however, there is limited information regarding the efficacy of 1L anti-EGFR therapy in mCRC pts with HER2 alterations. The PARADIGM trial demonstrated longer median OS with 1L PAN (anti-EGFR) vs BEV (anti–vascular endothelial growth factor), with mFOLFOX6, in RAS WT mCRC (NCT02394795). We evaluated the efficacy of PAN vs BEV in pts with HER2amp+ and HER2amp−, RAS WT mCRC from PARADIGM, taking into account primary tumor sidedness. Methods: Baseline plasma ctDNA was obtained from pts with RAS WT mCRC enrolled in PARADIGM; pts with evaluable pretreatment ctDNA were included in the biomarker analysis (NCT02394834). A custom panel (PlasmaSELECT-R 91, PGDx) was used to detect HER2amp+ and HER2amp− samples. OS, PFS, and response rate (RR) were compared in pts with HER2amp+ vs pts with HER2amp−. Results: Of 802 pts with RAS WT mCRC, 733 (91%) had evaluable pretreatment samples; 32 (4%) had HER2amp+ (PAN, n=19; BEV, n=13). A lack of a survival benefit with PAN vs BEV was suggested in pts with HER2amp+, regardless of tumor-sidedness (median OS: overall population, PAN, 23.0 mo; BEV, 26.7 mo; HR, 0.96; 95% CI: 0.45–2.04; left-sided population, PAN, 25.1 mo; BEV, 26.7 mo; HR, 0.89; 95% CI: 0.39–2.04]). Data in the right-sided population are not shown for pts with HER2amp+ due to the small sample size. In the overall population, there was a trend toward shorter OS for HER2amp+ vs HER2amp− pts (PAN: 23.0 vs 36.3 mo; HR, 1.57; 95% CI: 0.96–2.57; BEV: 26.7 vs 31.6 mo; HR, 1.41; 95% CI: 0.79–2.52). Median PFS and RR were similar between pts with HER2amp+ and HER2amp− in PAN or BEV arms (Table). Conclusions:HER2 amplification appears to be prognostic in pts with RAS WT mCRC but may not be predictive of a survival benefit of 1L PAN treatment over BEV. Clinical trial information: NCT02394834.
Population | HER2amp+ | HER2amp− | ||||
|---|---|---|---|---|---|---|
| PAN + mFOLFOX6 | BEV + mFOLFOX6 | HR (95% CI) | PAN + mFOLFOX6 | BEV + mFOLFOX6 | HR (95% CI) | |
| Overall, n | 19 | 13 | 349 | 352 | ||
| Median OS, mo | 23.0 | 26.7 | 0.96 (0.45–2.04) | 36.3 | 31.6 | 0.86 (0.72–1.01) |
| Median PFS, mo | 12.2 | 9.8 | 1.49 (0.63–3.49) | 12.3 | 11.5 | 1.06 (0.90–1.26) |
| RR, % | 73.7 | 69.2 | 1.24* (0.25–6.00) | 74.5 | 67.3 | 1.42* (1.02–1.97) |
| Left-sided, n | 16 | 11 | 271 | 256 | ||
| Median OS, mo | 25.1 | 26.7 | 0.89 (0.39–2.04) | 38.1 | 34.1 | 0.82 (0.67–1.00) |
| Median PFS, mo | 14.3 | 9.8 | 1.20 (0.48–3.02) | 13.1 | 12.1 | 1.00 (0.82–1.22) |
| RR, % | 75.0 | 63.6 | 1.71* (0.31–9.55) | 80.1 | 68.0 | 1.89* (1.28–2.83) |
| Right-sided, n | 3† | 2† | 75 | 89 | ||
| Median OS, mo | - | - | - | 22.0 | 25.5 | 1.11 (0.79–1.56) |
| Median PFS, mo | - | - | - | 8.0 | 10.6 | 1.46 (1.04–2.05) |
| R, % | - | - | - | 54.7 | 65.2 | 0.64* (0.34–1.21) |
*Odds ratio;†Not calculated due to small sample size.
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Abstract Details
Session Type
Poster Session
Session Title
Poster Session B
Track
Gastrointestinal Cancer,Gynecologic Cancer,Head and Neck Cancer,Quality of Care,Genetics/Genomics/Multiomics,Healthcare Equity and Access to Care,Healthtech Innovations,Models of Care and Care Delivery,Population Health,Viral-Mediated Malignancies
Sub Track
Targeted Therapies
Clinical Trial Registration Number
NCT02394834
Citation
JCO Global Oncology 9, 2023 (suppl 1; abstr 53)
DOI
10.1200/GO.2023.9.Supplement_1.53
Abstract #
53
Poster Bd #
C10
Abstract Disclosures
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