Adding panitumumab vs. bevacizumab to chemotherapy extends OS in colorectal cancer subset
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Key takeaways:
- Researchers reported the survival benefit among patients with left-sided tumors and the overall study population.
- Subgroup analyses showed no significant benefit among patients with right-sided tumors.
The addition of panitumumab vs. bevacizumab to standard first-line chemotherapy significantly extended OS for certain patients with RAS wild-type metastatic colorectal cancer, according to data published in JAMA.
“Although this study showed significant improvement of survival in the overall population, subgroup analysis suggested no significant difference in overall survival between treatments in patients with right-sided tumors, suggesting that the survival benefit was mainly among participants with left-sided tumors,” Jun Watanabe, MD, PhD, of the department of surgery in the gastroenterological center at Yokohama City University Medical Center in Japan, and colleagues wrote.
Background and methodology
The addition of anti-EGFR or anti-VEGF monoclonal antibodies to first-line doublet chemotherapy is frequently recommended for patients with RAS wild-type metastatic colorectal cancer; however, the optimal targeted therapy remains unclear.
Watanabe and colleagues conducted an open-label, phase 3 clinical trial to evaluate panitumumab (Vectibix, Amgen) or bevacizumab (Avastin, Genentech) added to standard first-line chemotherapy for treatment of patients with RAS wild-type, left-sided, metastatic colorectal cancer.
The researchers randomly assigned 823 patients to modified FOLFOX6 plus either panitumumab (n = 411) dosed at 6 mg/kg on day 1 as a 60-minute IV infusion or bevacizumab (n = 412) dosed at 5 mg/kg on day 1 as an IV infusion over 30 to 90 minutes, depending on the institution.
Researchers administered treatment every 14 days until progressive disease or unacceptable toxicity, participant withdrawal, physician decision to discontinue treatment for reasons other than disease progression or toxicity, or curative-intent surgery.
OS served as the primary endpoint, with PFS, response rate, duration of response and curative resection rate as secondary endpoints.
The trial took place at 197 sites in Japan from May 2015 to January 2022. Median follow-up was 61 months.
Results, implications
Among the as-treated population (n = 802; median age, 66 years; 35.2% women), 604 patients (75.3%) had left-sided tumors.
Researchers reported median OS of 37.9 months with panitumumab and 34.3 months with bevacizumab among patients with left-sided tumors (HR = 0.82; 95.798% CI, 0.68-0.99) and 36.2 months vs. 31.3 months in the overall population (HR = 0.84; 95% CI, 0.72-0.98).
Researchers also reported longer median PFS in the panitumumab group among patients with left-sided tumors (13.1 months vs. 11.9 months; HR = 1; 95% CI, 0.83-1.2) and the overall population (12.2 months vs. 11.4 months; HR = 1.05; 95% CI, 0.9-1.24).
Patients of the panitumumab group exhibited an 80.2% response rate vs. 68.6% for patients in the bevacizumab group among those with left-sided tumors (difference = 11.2%; 95% CI, 4.4-17.9) and 74.9% vs. 67.3% among the overall population (difference = 7.7%; 95% CI, 1.5-13.8).
The panitumumab group had a longer duration of response among those with left-sided tumors (13.1 months vs. 11.2 months ; HR = 0.86; 95% CI, 0.7-1.1) and the overall population (11.9 months vs. 10.7 months; HR =0.89; 95% CI ,0.74-1.06). Those who received the panitumumab regimen also had higher curative resection rates (left-sided tumors, 18.3% vs. 11.6%; difference = 6.6%; 95% CI, 1-12.3; overall population, 16.5% vs. 10.9%; difference = 5.6%; 95% CI, 1-10.3).
Common treatment-emergent adverse events included acneiform rash (panitumumab, 74.8%; bevacizumab, 3.2%), peripheral sensory neuropathy (70.8% vs. 73.7%) and stomatitis (61.6% vs. 40.5%).
Subgroup analyses indicated the survival benefit occurred largely among patients with left-sided tumors, which differ from right-sided tumors in histology, embryonic origin and sequence variation, researchers wrote.
“Right-sided tumors have increased frequencies of microsatellite instability, CpG island methylator phenotype, and BRAF variants,” they wrote. “Because survival curves showed no discernible difference between the two groups until 28 months, even in patients with left-sided tumors, additional biomarkers, such as BRAF, ERBB2 (HER2) and microsatellite instability, that may account for these differences warrant further investigation.”
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