The panitumumab regimen is a new first-line standard in wild-type RAS metastatic colorectal cancer
Yoshino T, et al. Summary LBA1. Presented at: ASCO Annual Meeting; June 3-7, 2022; Chicago.
Disclosures: Japan Medical Affairs, Japan Oncology Business Unit and Takeda Pharmaceutical Company Ltd. of Tokyo funded this study. Yoshino brings in fees from Bayer Yakuhin, Chugai Pharma, Merck, MSD KK, and Ono Pharmaceutical, as well as research funds 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 summary for all relevant financial disclosures from other researchers.
CHICAGO — Adding panitumumab over bevacizumab to standard dual chemotherapy significantly prolonged survival for patients with RAS wild-type and left-sided metastatic colorectal cancer, according to study results.
The panitumumab (Vectibix, Amgen) regimen conferred a median OS of more than 3 years——the longest survival ever reported in a prospective, first-line Phase 3 trial in unresectable metastatic colorectal cancer, showed results presented at the of the ASCO annual meeting.
“These results have established a standard first-line combination therapy regimen for patients with RAS wild-type metastatic left-sided colorectal cancer, Takayuki Yoshino, MD, PhD, from the Department of Gastroenterology and Gastrointestinal Oncology at the National Cancer Center Hospital East in Chiba, Japan, said during a press briefing at the ASCO annual meeting.
Adding an anti-epidermal growth factor receptor (EGFR) or an anti-VEGF antibody to chemotherapy has been shown to prolong OS for up to 30 months in patients with colorectal cancer unresectable metastasis, Yoshino said. The PARADIGM study represented the first prospective trial comparing 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 primary tumors on the left side.
The open-label, multicenter trial in Japan included 802 chemotherapy-naïve 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 and then among those in the full analysis set – served as the primary endpoint. The researchers assessed PFS, response rate, and curative resection rate as secondary endpoints.
The median follow-up was 61 months.
The panitumumab regimen significantly prolonged OS compared to the bevacizumab regimen in both patients with primary left-sided tumors (median, 37.9 months versus 34.3 months; HR=0.82; 95 CI .79%, 0.68-0.99) and the overall population (median, 36.2 months versus 31.3 months; RR = 0.84; 95% CI, 0.72-0.98). OS did not differ significantly between 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 versus 13.2 months; overall population, 12.9 months versus 12 months), but those who received panitumumab had response rates higher (left side, 80.2% vs 68.6%; overall, 74.9% vs 67.3%) and curative resection (left side, 18.3% vs 11.6%; overall, 16.5 % vs. 10.9%).
The researchers observed no new safety signals.
Biomarker analysis is underway 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.