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

• DOI: 10.1001/jama.2023.4428
• Publication Date: 2023-04-18T15:54:44Z
• Authors: Jun Watanabe; Kei Muro; Kohei Shitara; Kentaro Yamazaki; Manabu Shiozawa; Hisatsugu Ohori; Atsuo Takashima; Mitsuru Yokota; Akitaka Makiyama; Naoya Akazawa; Hitoshi Ojima; Yasuhiro Yuasa; Keisuke Miwa; Hirofumi Yasui; Eiji Oki; Takeo Sato; Takeshi Naitoh; Yoshito Komatsu; Takeshi Kato; Masamitsu Hihara; Junpei Soeda; Toshihiro Misumi; Kouji Yamamoto; Kiwamu Akagi; Atsushi Ochiai; Hiroyuki Uetake; Katsuya Tsuchihara; Takayuki Yoshino
• Keywords: Panitumumab; Clinical endpoint; Progression-free survival

For patients with RAS wild-type metastatic colorectal cancer, adding anti-epidermal growth factor receptor (anti-EGFR) or anti-vascular endothelial (anti-VEGF) monoclonal antibodies to first-line doublet chemotherapy is routine, but the optimal targeted therapy has not been defined.To evaluate effect of panitumumab (an anti-EGFR antibody) vs bevacizumab anti-VEGF standard for treatment wild-type, left-sided, cancer.Randomized, open-label, phase 3 clinical trial at 197 sites in Japan May 2015-January 2022 among 823 chemotherapy-naive unresectable cancer (final follow-up, January 14, 2022).Panitumumab (n = 411) 412) plus modified fluorouracil, l-leucovorin, and oxaliplatin (mFOLFOX6) every 14 days.The primary end point, overall survival, was tested first participants left-sided tumors, then population. Secondary points were progression-free response rate, duration response, curative (defined as R0 status) resection rate.In as-treated population 802; median age, 66 years; 282 [35.2%] women), 604 (75.3%) had tumors. Median follow-up 61 months. survival 37.9 months 34.3 tumors (hazard ratio [HR] death, 0.82; 95.798% CI, 0.68-0.99; P .03) 36.2 31.3 months, respectively, (HR, 0.84; 95% 0.72-0.98; .03). 13.1 11.9 those 1.00; 0.83-1.20) 12.2 11.4 1.05; 0.90-1.24). Response rates 80.2% 68.6%, (difference, 11.2%; 4.4%-17.9%) 74.9% 67.3% 7.7%; 1.5%-13.8%). 11.2 0.86; 0.70-1.10) 10.7 0.89; 0.74-1.06). Curative 18.3% 11.6% tumors; 6.6%; 1.0%-12.3%) 16.5% 10.9% 5.6%; 1.0%-10.3%). Common treatment-emergent adverse events acneiform rash (panitumumab: 74.8%; bevacizumab: 3.2%), peripheral sensory neuropathy 70.8%; 73.7%), stomatitis 61.6%; 40.5%).Among panitumumab, compared bevacizumab, significantly improved population.ClinicalTrials.gov Identifier: NCT02394795.