Yoshino T, et al. Abstract LBA1. Presented at: ASCO Annual Meeting; June 3-7, 2022; Chicago.
Japan Medical Affairs, Japan Oncology Business Unit and Takeda Pharmaceutical Company Ltd. of Tokyo funded this study. Yoshino reports honoraria from Bayer Yakuhin, Chugai Pharma, Merck, MSD K.K. and Ono Pharmaceutical, as well as research funding to his institution from Amgen, Chugai Pharma, Daiichi Sankyo Co, Ltd., Genomedia, Merck Sharp & Dohme, Nippon Boehringer Ingelheim, Ono Pharmaceutical, Pfizer, Sanofi, Sysmex and Taiho Pharmaceutical. Please see the abstract for all other researchers’ relevant financial disclosures.
CHICAGO — The addition of panitumumab vs. bevacizumab to standard doublet chemotherapy significantly extended survival among patients with RAS wild-type and left-sided metastatic colorectal cancer, according to study results.
The panitumumab (Vectibix, Amgen) regimen conferred median OS of more than 3 years —— the longest survival ever reported in a first-line, prospective phase 3 trial in unresectable metastatic colorectal cancer, findings presented at ASCO Annual Meeting showed.
“These results established a standard first-line combination regimen for patients with RAS wild-type, left-sided metastatic colorectal cancer,” Takayuki Yoshino, MD, PhD, of the department of gastroenterology and gastrointestinal oncology at National Cancer Center Hospital East in Chiba, Japan, said during a press briefing at ASCO Annual Meeting.
The addition of an anti-epidermal growth factor receptor (EGFR) or anti-VEGF antibody to chemotherapy has been shown extend OS as much as 30 months among patients with unresectable metastatic colorectal cancer, Yoshino said. The PARADIGM study represented the first prospective trial to compare an anti-EGFR antibody, panitumumab, with an anti-VEGF antibody, bevacizumab (Avastin, Genentech), when added to standard chemotherapy for patients with RAS wild-type disease and left-sided primary tumors.
The open-label, multicenter trial conducted in Japan included 802 chemotherapy-naive patients recruited between May 2015 and June 2017. Researchers randomly assigned patients to modified FOLXFOX6 chemotherapy, which includes folinic acid, fluorouracil and oxaliplatin, with either panitumumab (n = 400) or bevacizumab (n = 402). A similar number of patients in the panitumumab and bevacizumab groups had left-sided primary tumors (n = 312 vs. 292).
OS — tested hierarchically among patients with left-sided tumors, then among those in the full analysis set — served as the primary endpoint. Researchers evaluated PFS, response rate and curative resection rate as secondary endpoints.
Median follow-up was 61 months.
The panitumumab regimen significantly extended OS vs. the bevacizumab regimen both among patients with left-sided primary tumors (median, 37.9 months vs. 34.3 months; HR = 0.82; 95.79% CI, 0.68-0.99) and the overall population (median, 36.2 months vs. 31.3 months; HR = 0.84; 95% CI, 0.72-0.98). OS did not differ significantly between the groups for those with right-sided tumors (HR = 1.09).
The panitumumab and bevacizumab groups had similar median PFS (left-sided tumors, 13.7 months vs. 13.2 months; overall population, 12.9 months vs. 12 months), but those who received panitumumab had higher rates of response (left-sided, 80.2% vs. 68.6%; overall, 74.9% vs. 67.3%) and curative resection (left-sided, 18.3% vs. 11.6%; overall, 16.5% vs. 10.9%).
Researchers observed no new safety signals.
A biomarker analysis is being conducted using tumor tissue and plasma samples collected from trial participants before and after treatment.
“The results will be available in the future at an upcoming international meeting,” Yoshino said.