Panitumumab Plus mFOLFOX6 Significantly Improves OS in Metastatic Colorectal Cancer

Panitumumab combined with modified leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin (mFOLFOX6) significantly improved overall survival (OS) vs bevacizumab plus mFOLFOX6 for patients with RAS wild-type and left-sided metastatic colorectal cancer, according to findings from the phase 3 PARADIGM trial.

These findings were presented by Kei Muro, MD, Aichi Cancer Center Hospital, Nagoya, Japan, at the 2022 ESMO World Congress on Gastrointestinal Cancer.

The open-label, multicenter trial conducted in Japan enrolled 823 patients with chemotherapy-naïve RAS wild-type and left-sided metastatic colorectal cancer from May 2015 to June 2017. Patients were randomized in a 1:1 ratio to receive panitumumab plus mFOLFOX6 (n = 400) or bevacizumab plus mFOLFOX6 (n = 402).

The primary end point of the trial was OS. Secondary end points included progression-free survival (PFS), response rate, and curative resection (R0) rate in the left-sided and overall population.

Of the 802 patients randomized on the trial, 312 patients in the panitumumab group and 292 patients in the bevacizumab group had left-sided primary tumors. Baseline characteristics were well-balanced between the two treatment arms in the overall population.

Researchers analyzed OS after 448 OS events in patients with left-sided tumors with a median follow-up of 61 months. In both the left-sided population and overall population, OS was significantly improved with panitumumab vs bevacizumab. The hazard ratio (HR) for death for panitumumab vs bevacizumab was 0.82 (95.798% confidence interval [CI], 0.68 to 0.99; P = .031) in the left-sided population and 0.84 (95% CI, 0.72 to 0.98; P = .030) in the overall population.

In patients with left-sided tumors, PFS was 13.7 (95% CI, 12.7 to 15.3) months in the panitumumab arm, which was comparable to that seen in the bevacizumab arm (13.2 months [95% CI, 11.4 to 14.5]; HR, 0.98 [95% CI, 0.82 to 1.17]). However, response rate and R0 rate were higher with panitumumab vs bevacizumab. The response rate was 80.2% (95% CI, 75.3 to 84.5) with panitumumab vs 68.6% (95% CI, 62.9 to 74) with bevacizumab. R0 rates were 18.3% (95% CI, 14.1 to 23) and 11.6% (95% CI, 8.2 to 15.9), respectively.

In the overall population, PFS was 12.9 months (95% CI, 11.3 to 13.6) in the panitumumab arm vs 12 months (95% CI, 11.3 to 13.5) in the bevacizumab arm (HR, 1.01 [95% CI, 0.87 to 1.18]). The response rates were 74.9% (95% CI, 70.3 to 79.1) and 67.3% (95% CI, 62.4 to 71.9), respectively, and R0 rates were 16.5% (95% CI, 13 to 20.5) and 10.9% (95% CI, 8.1 to 14.4), respectively.

Results from an exploratory analysis assessing panitumumab vs bevacizumab in patients with right-sided tumors showed no significant difference in survival.

“In patients with RAS wild-type and left-sided metastatic colorectal cancer, the combination of panitumumab with mFOLFOX6 significantly improved OS vs bevacizumab with mFOLFOX6, establishing a standard first-line combination regimen for this population,” Dr Muro concluded.

Source:

Muro K, Watanabe J, Shitara K, et al. First-line panitumumab versus bevacizumab in combination with mFOLFOX6 for RAS wild-type metastatic colorectal cancer: PARADIGM trial results. Presented at: ESMO World Congress on Gastrointestinal Cancer; June 29-July 2, 2022. Barcelona, Spain. Abstract LBA O-10.