Colon to Rectum
JAMA. 2023;329(15):1271−82
Panitumumab versus bevacizumab added to standard first-line chemotherapy and overall survival among patients with RAS wild-type, left-sided metastatic colorectal cancer: A randomized clinical trial
Importance: For patients with RAS wild-type metastatic colorectal cancer (CRC), adding anti-epidermal growth factor receptor (anti-EGFR) or anti-vascular endothelial growth factor (anti-VEGF) monoclonal antibodies to first-line doublet chemotherapy is routine, but the optimal targeted therapy has not been defined.
Objective: To evaluate the effect of adding panitumumab (an anti-EGFR monoclonal antibody) versus bevacizumab (an anti-VEGF monoclonal antibody) to standard first-line chemotherapy for treatment of RAS wild-type, left-sided, metastatic CRC.
Design, setting, and participants: Randomized, open-label, phase 3 clinical trial at 197 sites in Japan in May 2015 to January 2022 among 823 patients with chemotherapy-naive RAS wild-type, unresectable metastatic CRC (final follow-up, January 14, 2022). Interventions: Panitumumab (n = 411) or bevacizumab (n = 412) plus modified fluorouracil, l-leucovorin, and oxaliplatin (mFOLFOX6) every 14 days.
Main outcomes and measures: The primary end point, overall survival, was tested first in participants with left-sided tumors, then in the overall population. Secondary end points were progression-free survival, response rate, duration of response, and curative (defined as R0 status) resec-tion rate.
Results: In the as-treated population (n = 802; median age, 66 years; 282 [35.2%] women), 604 (75.3%) had left-sided tumors. Median fol-low-up was 61 months. Median overall survival was 37.9 months with panitumumab versus 34.3 months with bevacizumab in participants with left-sided tumors (hazard ratio [HR] for death = 0.82; 95.798% confidence interval [CI]: 0.68−0.99; p = 0.03) and 36.2 versus 31.3 months, re-spectively, in the overall population (HR = 0.84; 95% CI: 0.72−0.98; p = 0.03). Median progression-free survival for panitumumab versus bevaci-zumab was 13.1 versus 11.9 months, respectively, for those with left-sided tumors (HR = 1.00; 95% CI: 0.83−1.20) and 12.2 versus 11.4 months overall (HR = 1.05; 95% CI: 0.90−1.24). Response rates with panitumumab versus bevacizumab were 80.2% versus 68.6%, respectively, for left-sided tumors (difference, 11.2%; 95% CI: 4.4−17.9%) and 74.9% versus 67.3% overall (difference, 7.7%; 95% CI: 1.5−13.8%). Median dura-tion of response with panitumumab versus bevacizumab was 13.1 versus 11.2 months for left-sided tumors (HR = 0.86; 95% CI: 0.70−1.10) and 11.9 versus 10.7 months overall (HR = 0.89; 95% CI: 0.74−1.06). Curative resection rates with panitumumab versus bevacizumab were 18.3% versus 11.6% for left-sided tumors (difference, 6.6%; 95% CI: 1.0−12.3%) and 16.5% versus 10.9% overall (difference, 5.6%; 95% CI: 1.0−10.3%). Common treatment-emergent adverse events were acneiform rash (panitumumab: 74.8%; bevacizumab: 3.2%), peripheral sensory neuropathy (panitumumab: 70.8%; bevacizumab: 73.7%), and stomatitis (panitumumab: 61.6%; bevacizumab: 40.5%).
Conclusions and relevance: Among patients with RAS wild-type metastatic colorectal cancer, adding panitumumab, compared with bevacizumab, to standard first-line chemotherapy significantly improved overall survival in those with left-sided tumors and in the overall population.