Meeting
2023 ASCO Annual Meeting
Efficacy of panitumumab in patients with left-sided disease, MSS/MSI-L, and RAS/BRAF WT: A biomarker study of the phase III PARADIGM trial.
Authors
Kentaro Yamazaki
Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan
Kentaro Yamazaki , Kei Muro , Jun Watanabe , Kohei Shitara , 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
Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, 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, Kashiwa, Japan, Division of Medical Oncology, Japanese Red Cross Ishinomaki Hospital, Miyagi, Japan, Division of Gastrointestinal Surgery, Kanagawa Cancer Center, Kanagawa, 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, 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 Limited, Tokyo, Japan
Background: The PARADIGM trial (NCT02394795) 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). Based on current guideline recommendations regarding clinically relevant biomarkers, here we report clinical outcomes in left-sided mCRC pts with microsatellite stable or microsatellite instability low (MSS/MSI-L) and RAS (KRAS/NRAS)/BRAF (V600E) WT from PARADIGM. Methods: Baseline plasma circulating tumor DNA (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). The efficacy (OS, progression-free survival [PFS], response rate [RR], and curative resection rate [R0]) of PAN plus mFOLFOX6 compared with BEV plus mFOLFOX6 according to RAS, BRAF (V600E), and MSI status and primary tumor location was evaluated. Results: Among 802 pts in the full analysis set, 733 (91%) had evaluable pretreatment samples for ctDNA analysis. Of these pts, 53 (7.2%) and 78 (10.6%) pts had RAS and BRAF (V600E) mutations, respectively, and 20 (2.7%) pts had MSI high (MSI-H) status. In left-sided mCRC pts with MSS/MSI-L and RAS/BRAF WT, OS tended to be longer with PAN vs BEV (40.6 [95% CI, 36.3-44.4] vs 34.8 [95% CI, 31.3-41.2] months, respectively; HR, 0.79 [95% CI, 0.64–0.97]). Although PFS was comparable between PAN (13.6 months [95% CI, 12.6–15.3]) and BEV (12.6 months [95% CI, 11.3–14.1]; HR, 0.95 [95% CI, 0.77–1.17]), RR and R0 resection rates were higher with PAN (RR: 83.2% [95% CI, 78.0–87.6]; R0: 18.8% [95% CI: 14.2–24.1]) compared with BEV (RR: 66.4% [95% CI, 60.0–72.3]; R0: 10.0% [95% CI: 6.5–14.5]). OS was similar or inferior to PAN vs BEV regardless of the primary sidedness in pts with MSI-H or RAS/BRAF mutations (Table). Conclusions: These results support PAN + mFOLFOX6 as a first-line therapy for left-sided pts with MSS/MSI-L and RAS/BRAF WT. Clinical trial information: NCT02394795.
| MSS/MSI-L and RAS/BRAF WT | MSI-H or RAS/BRAF mutation | |||||
|---|---|---|---|---|---|---|
| Population | PAN + mFOLFOX6 | BEV + mFOLFOX6 | Difference; HR (95% CI) | PAN + mFOLFOX6 | BEV + mFOLFOX6 | Difference; HR (95% CI) |
| Left-sided, n | 256 | 241 | 31 | 26 | ||
| Median OS, mo (95% CI) | 40.6 (36.3–44.4) | 34.8 (31.3–41.2) | 5.8; 0.79 (0.64–0.97) | 15.4 (9.6–20.9) | 25.2 (17.0–30.9) | −9.8; 1.53 (0.84–2.76) |
| Right-sided, n | 41 | 55 | 37 | 36 | ||
| Median OS, mo (95% CI) | 37.9 (22.0–42.2) | 30.9 (23.2–35.4) | 7.0; 0.94 (0.60–1.48) | 13.7 (11.3–18.7) | 17.9 (11.6–22.4) | −4.2; 1.28 (0.78–2.11) |
| Overall, n | 299 | 299 | 69 | 66 | ||
| Median OS, mo (95% CI) | 39.0 (36.3–43.3) | 34.1 (31.1–37.6) | 4.9; 0.79 (0.66–0.96) | 14.6 (11.3–18.8) | 19.8 (15.3–25.5) | −5.2; 1.27 (0.88–1.84) |
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Abstract Details
Session Type
Oral Abstract Session
Session Title
Gastrointestinal Cancer—Colorectal and Anal
Track
Gastrointestinal Cancer—Colorectal and Anal
Sub Track
Epidemiology/Outcomes
Clinical Trial Registration Number
NCT02394795
Citation
J Clin Oncol 41, 2023 (suppl 16; abstr 3508)
DOI
10.1200/JCO.2023.41.16_suppl.3508
Abstract #
3508
Abstract Disclosures
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