Panitumumab (PAN) plus mFOLFOX6 versus bevacizumab (BEV) plus mFOLFOX6 as first-line treatment in patients with <i>RAS</i> wild-type (WT) metastatic colorectal cancer (mCRC): Results from the phase 3 PARADIGM trial.
Takayuki Yoshino, Jun Watanabe, Kohei Shitara, Hirofumi Yasui, Hisatsugu Ohori, Manabu Shiozawa, Kentaro Yamazaki, Eiji Oki, Takeo Sato, Takeshi Naitoh, Yoshito Komatsu, Takeshi Kato, Masamitsu Hihara, Junpei Soeda, Kouji Yamamoto, Kiwamu Akagi, Atsushi Ochiai, Hiroyuki Uetake, Katsuya Tsuchihara, Kei Muro
Abstract
LBA1 Background: PARADIGM is the first prospective trial to test the superiority of PAN vs. BEV in combination with standard doublet first-line chemotherapy for patients (pts) with RAS WT mCRC and left-sided primary tumors. Methods: This open-label, multicenter trial in Japan (NCT02394795) randomly selected pts with chemotherapy-naive RAS WT mCRC to PAN + mFOLFOX6 or BEV + mFOLFOX6. Overall survival (OS) as primary endpoint was hierarchically tested in patients with left-sided tumors, followed by those in the full-analysis set (FAS) population. Key secondary endpoints included progression-free survival (PFS), response rate (RR), and curative resection (R0) rate. Results: From May 2015 to June 2017, 823 pts were randomized; 12 did not receive protocol treatment and 9 were excluded due to major deviation of inclusion criteria. A total of 400 pts received PAN and 402 pts received BEV as FAS; 312 and 292 pts had left-sided primary tumors, respectively. OS was analyzed after 448 OS events in left-sided pts with a median follow-up of 61 months. PAN significantly improved OS vs. BEV in both populations: left-sided (HR, 0.82; 95.798% CI, 0.68-0.99, p = .031, which crossed the boundary of significance [0.042]), and FAS (HR, 0.84; 95% CI, 0.72-0.98; p = .030, with < 0.05 as the boundary). Although PFS was comparable between treatment groups, RR and R0 resection rates were higher with PAN compared with BEV (Table). HR for OS in the right-sided population was 1.09. No new safety signal was observed. Conclusions: PAN significantly improved OS vs. BEV in combination with mFOLFOX6 in pts with RAS WT and left-sided mCRC, establishing a standard first-line combination regimen for this population. Clinical trial information: NCT02394795. [Table: see text]