Panitumumab vs Bevacizumab Added to Standard First-line Chemotherapy and Overall Survival Among Patients With RAS Wild-type, Left-Sided Metastatic Colorectal Cancer

Author(s): Jun Watanabe, MD, PhD1; Kei Muro, MD, PhD2; Kohei Shitara, MD, PhD3,4; Kentaro Yamazaki, MD, PhD5; Manabu Shiozawa, MD, PhD6; Hisatsugu Ohori, MD, PhD7; Atsuo Takashima, MD, PhD8; Mitsuru Yokota, MD, PhD9; Akitaka Makiyama, MD, PhD10; Naoya Akazawa, MD11; Hitoshi Ojima, MD, PhD12; Yasuhiro Yuasa, MD, PhD13; Keisuke Miwa, MD, PhD14; Hirofumi Yasui, MD, PhD5; Eiji Oki, MD, PhD15; Takeo Sato, MD, PhD16; Takeshi Naitoh, MD, PhD17; Yoshito Komatsu, MD, PhD18; Takeshi Kato, MD, PhD19; Masamitsu Hihara, MS20; Junpei Soeda, MD, PhD20; Toshihiro Misumi, PhD21; Kouji Yamamoto, PhD21; Kiwamu Akagi, MD, PhD22; Atsushi Ochiai, MD, PhD23,24; Hiroyuki Uetake, MD, PhD25; Katsuya Tsuchihara, MD, PhD26; Takayuki Yoshino, MD, PhD3
Source: JAMA. 2023;329(15):1271-1282. doi:10.1001/jama.2023.4428
Maem Hussein MD

Dr. Maen Hussein's Thoughts

In this study, Cetuximab beat Bevacizumab in left sided KRAS wild type colon cancer.

IMPORTANCE

For patients with RAS wild-type metastatic colorectal cancer, adding anti–epidermal growth factor receptor (anti-EGFR) or anti–vascular endothelial growth factor (anti-VEGF) monoclonal antibodies to first-line doublet chemotherapy is routine, but the optimal targeted therapy has not been defined.

OBJECTIVE

To evaluate the effect of adding panitumumab (an anti-EGFR monoclonal antibody) vs bevacizumab (an anti-VEGF monoclonal antibody) to standard first-line chemotherapy for treatment of RAS wild-type, left-sided, metastatic colorectal cancer.

DESIGN, SETTING, AND PARTICIPANT

Randomized, open-label, phase 3 clinical trial at 197 sites in Japan in May 2015–January 2022 among 823 patients with chemotherapy-naive RAS wild-type, unresectable metastatic colorectal cancer (final follow-up, January 14, 2022).

INTERVENTIONS

Panitumumab (n = 411) or bevacizumab (n = 412) plus modified fluorouracil, l-leucovorin, and oxaliplatin (mFOLFOX6) every 14 days.

MAIN OUTCOMES AND MEASURES

The primary end point, overall survival, was tested first in participants with left-sided tumors, then in the overall population. Secondary end points were progression-free survival, response rate, duration of response, and curative (defined as R0 status) resection rate.

RESULTS

In the as-treated population (n = 802; median age, 66 years; 282 [35.2%] women), 604 (75.3%) had left-sided tumors. Median follow-up was 61 months. Median overall survival was 37.9 months with panitumumab vs 34.3 months with bevacizumab in participants with left-sided tumors (hazard ratio [HR] for death, 0.82; 95.798% CI, 0.68-0.99; P = .03) and 36.2 vs 31.3 months, respectively, in the overall population (HR, 0.84; 95% CI, 0.72-0.98; P = .03). Median progression-free survival for panitumumab vs bevacizumab was 13.1 vs 11.9 months, respectively, for those with left-sided tumors (HR, 1.00; 95% CI, 0.83-1.20) and 12.2 vs 11.4 months overall (HR, 1.05; 95% CI, 0.90-1.24). Response rates with panitumumab vs bevacizumab were 80.2% vs 68.6%, respectively, for left-sided tumors (difference, 11.2%; 95% CI, 4.4%-17.9%) and 74.9% vs 67.3% overall (difference, 7.7%; 95% CI, 1.5%-13.8%). Median duration of response with panitumumab vs bevacizumab was 13.1 vs 11.2 months for left-sided tumors (HR, 0.86; 95% CI, 0.70-1.10) and 11.9 vs 10.7 months overall (HR, 0.89; 95% CI, 0.74-1.06). Curative resection rates with panitumumab vs bevacizumab were 18.3% vs 11.6% for left-sided tumors; (difference, 6.6%; 95% CI, 1.0%-12.3%) and 16.5% vs 10.9% overall (difference, 5.6%; 95% CI, 1.0%-10.3%). Common treatment-emergent adverse events were acneiform rash (panitumumab: 74.8%; bevacizumab: 3.2%), peripheral sensory neuropathy (panitumumab: 70.8%; bevacizumab: 73.7%), and stomatitis (panitumumab: 61.6%; bevacizumab: 40.5%).

CONCLUSIONS AND RELEVANCE

Among patients with RAS wild-type metastatic colorectal cancer, adding panitumumab, compared with bevacizumab, to standard first-line chemotherapy significantly improved overall survival in those with left-sided tumors and in the overall population.

Author Affiliations

1Department of Surgery, Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan2Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan3Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan4Department of Immunology, Nagoya University Graduate School of Medicine, Aichi, Japan5Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan6Division of Gastrointestinal Surgery, Kanagawa Cancer Center, Kanagawa, Japan7Division of Medical Oncology, Japanese Red Cross Ishinomaki Hospital, Miyagi, Japan8Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan9Department of General Surgery, Kurashiki Central Hospital, Okayama, Japan10Department of Hematology/Oncology, Japan Community Healthcare Organization, Fukuoka, Japan11Department of Gastrointestinal Surgery, Sendai City Medical Center, Sendai Open Hospital, Miyagi, Japan12Department of Gastroenterological Surgery, Gunma Prefectural Cancer Center, Gunma, Japan13Department of Gastroenterological Surgery, Japanese Red Cross Tokushima Hospital, Tokushima, Japan14Department of Cancer Multimodel Therapy Center, Kurume University Hospital, Fukuoka, Japan15Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan16Research and Development Center for Medical Education, Department of Clinical Skills Education, Kitasato University School of Medicine, Sagamihara, Japan17Department of Lower Gastrointestinal Surgery, Kitasato University School of Medicine, Sagamihara, Japan18Division of Cancer Chemotherapy, Hokkaido University Hospital Cancer Center, Sapporo, Japan19Department of Surgery, National Hospital Organization Osaka National Hospital, Osaka, Japan20Japan Medical Affairs, Japan Oncology Business Unit, Takeda Pharmaceutical Company Ltd, Tokyo, Japan21Department of Biostatistics, Yokohama City University School of Medicine, Yokohama, Japan22Division of Molecular Diagnosis and Cancer Prevention, Saitama Cancer Center, Saitama, Japan23Pathology Division, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Chiba, Japan24now with the Research Institute for Biomedical Sciences, Tokyo University of Science, Tokyo, Japan25National Hospital Organization, Disaster Medical Center, Tokyo, Japan26Division of Translational Informatics, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Chiba, Japan

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