Meeting
2023 ASCO Gastrointestinal Cancers Symposium
Negative hyperselection of patients with RAS wild-type metastatic colorectal cancer for panitumumab: A biomarker study of the phase III PARADIGM trial.
Authors
Kohei Shitara
Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, Japan;
Kohei Shitara , Kei Muro , Jun Watanabe , Kentaro Yamazaki , Hisatsugu Ohori , Manabu Shiozawa , Hirofumi Yasui , Eiji Oki , 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 Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, Japan; , Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan; , Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan; , Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan; , Division of Medical Oncology, Japanese Red Cross Ishinomaki Hospital, Ishinomaki, Japan; , Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan; , Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 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, Kashiwa, 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; , Division of Translational Informatics, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Chiba, Japan; , Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan;
Research Funding
Pharmaceutical/Biotech Company
Takeda Pharmaceutical Company Limited, Tokyo, Japan
Background: The PARADIGM trial showed longer median overall survival (OS) with first-line mFOLFOX6 plus panitumumab (PAN) vs bevacizumab (BEV) in patients (pts) with RAS wild type (WT) and left-sided metastatic colorectal cancer (mCRC) (37.9 vs 34.3 months, respectively; hazard ratio [HR], 0.82; P=0.031) and similar OS in right-sided pts (HR 1.09; Yoshino T, et al. ASCO 2022 LBA1). We evaluated the usefulness of negative hyperselection by gene alterations in ctDNA related to primary resistance to anti-EGFR therapy. Methods: Baseline plasma ctDNA (>10 ng/mL and >10 nM DNA) from pts enrolled in the biomarker study (NCT02394834) was assessed using a custom panel (PlasmaSELECT-R 91, PGDx). Preplanned gene alterations for hyperselection included KRAS, NRAS,PTEN, and extracellular domain EGFR mutations, HER2 and MET amplifications, and ALK, RET, or NTRK1 fusions. Results: Among 802 pts in the full analysis set, 733 (91%) had evaluable pretreatment samples for ctDNA analysis. Of these pts, 204 (28%) had at least 1 gene alteration, including KRAS/NRAS (8%), BRAFV600E (11%), PTEN (5%), EGFR (3%), HER2 (5%), MET (1%), and fusions (1%). In 529 (72%) hyperselected pts without any gene alterations, OS tended to be longer with PAN vs BEV regardless of primary sidedness; the OS HRs ranged from 0.76 to 0.82, and the median OS gains ranged from 6.6 to 8.0 months (Table). Meanwhile, OS was similar or inferior with PAN vs BEV irrespective of the primary sidedness in pts with any of these gene alterations (Table). Conclusions: Negative hyperselection using ctDNA rather than tumor sidedness may identify appropriate pts for first-line PAN over BEV. These results warrant further validation in additional cohorts. Clinical trial information: NCT02394834.
| Population | Hyperselection Negative | Hyperselection Positive | ||||
|---|---|---|---|---|---|---|
| PAN + mFOLFOX6 | BEV + mFOLFOX6 | Difference; HR (95% CI) | PAN + mFOLFOX6 | BEV + mFOLFOX6 | Difference; HR (95% CI) | |
| Left-sided, n | 221 | 218 | 6.6; 0.76 (0.61–0.94) | 66 | 49 | −2.8; 1.10 (0.72–1.66) |
| Median OS, mo (95% CI) | 42.1 (37.0–49.6) | 35.5 (31.6–41.5) | 23.7 (17.5–30.9) | 26.4 (20.8–30.9) | ||
| Overall, n | 258 | 271 | 6.9; 0.75 (0.62–0.92) | 110 | 94 | −3.2; 1.14 (0.84–1.54) |
| Median OS, mo (95% CI) | 41.4 (37.1–48.1) | 34.4 (31.3–40.3) | 18.7 (14.8–23.0) | 22.2 (19.1–27.7) | ||
| Right-sided, n | 36 | 50 | 8.0; 0.82 (0.50–1.35) | 43 | 41 | −4.4; 1.33 (0.84–2.11) |
| Median OS, mo (95% CI) | 38.9 (26.5–52.2) | 30.9 (22.5–36.1) | 14.1 (11.3–18.7) | 18.5 (11.6–25.5) | ||
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Abstract Details
Session Type
Poster Session
Session Title
Poster Session C: Cancers of the Colon, Rectum, and Anus
Track
Colorectal Cancer,Anal Cancer
Sub Track
Tumor Biology, Biomarkers, and Pathology
Clinical Trial Registration Number
NCT02394834
Citation
J Clin Oncol 41, 2023 (suppl 4; abstr 11)
DOI
10.1200/JCO.2023.41.4_suppl.11
Abstract #
11
Poster Bd #
A4
Abstract Disclosures
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