Patients with RAS wild-type metastatic colorectal cancer (mCRC) had a significant improvement in overall survival (OS) when modified FOLFOX6 (mFOLFOX6) was combined with panitumumab instead of bevacizumab, a phase 3 study showed.

These findings were presented at the 2022 ASCO Annual Meeting by Takayuki Yoshino, MD, PhD, of the National Cancer Center Hospital East in Japan.

The phase 3 PARADIGM study ( Identifier: NCT02394795), conducted in Japan, included patients with chemotherapy-naive RAS wild-type mCRC. Patients were randomly assigned to receive either mFOLFOX6 with panitumumab or mFOLFOX6 with bevacizumab.

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The primary study endpoint was OS, which was evaluated in patients with left-sided tumors. If the result for this endpoint was significant for left-sided tumors, then the full study population was evaluated. Key secondary endpoints included progression-free survival (PFS), response rate, and curative resection rate (R0).

A total of 823 patients were included in the study, with 404 patients receiving panitumumab and 407 receiving bevacizumab. Of these patients, left-sided tumors were present in most, totaling 312 patients who received panitumumab and 292 who received bevacizumab.

At a median follow-up of 61 months, OS was significantly better with panitumumab in both the population with left-sided tumors and in the overall study population. The stratified hazard ratio (HR) for death with panitumumab, compared with bevacizumab, was 0.82 (P =.031) in the left-sided tumor population. It was 0.84 (P =.030) in the full analysis population. The median OS for the population with left-sided tumors was 37.9 months in the arm receiving panitumumab and 34.3 months for the arm receiving bevacizumab. 

The median PFS was not significantly different between treatment groups in the population with left-sided tumors. The median PFS was 13.7 months with panitumumab and 13.2 months with bevacizumab.

The response rate was 80.2% with panitumumab and 68.6% with bevacizumab in the left-sided tumor population. The R0 rate was 18.3% with panitumumab and 11.6% with bevacizumab in this group.

OS rates for each treatment arm were also compared for patients with right-sided tumors, and the stratified HR for death was 1.09. 

The investigators reported that there were no new safety signals observed. They also concluded that the study demonstrated superiority with the use of panitumumab vs bevacizumab in combination with mFOLFOX6 for left-sided tumor and the overall mCRC population.

“These results support panitumumab plus modified FOLFOX6 in the first-line setting for patients with RAS wild-type and left-sided metastatic colorectal cancer,” Dr Yoshino concluded, adding that biomarker analyses are ongoing.

Disclosures: Some study authors declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.


Yoshino T, Watanabe J, Shitara K, et al. Panitumumab (PAN) plus mFOLFOX6 versus bevacizumab (BEV) plus mFOLFOX6 as first-line treatment in patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC): Results from the phase 3 PARADIGM trial. Presented at ASCO 2022; June 3-7, 2022. Abstract LBA1.