Panitumumab Boosts Survival in Advanced Colorectal Cancer

Treatment with the anti-EGFR panitumumab plus mFOLFOX6 resulted in improved overall survival compared with the anti-VEGF bevacizumab plus mFOLFOX6 in patients with wild-type KRAS exon 2 metastatic colorectal cancer, according to the results of the phase II PEAK trial published recently in the Journal of Clinical Oncology.

A secondary analysis also found that patients with wild-type RAS experienced improved progression-free survival with the panitumumab-containing regimen.

According to Lee S. Schwartzberg, MD, of West Clinic, Memphis, Tenn., and colleagues these results echo the results of the FIRE-3 trial that showed that the anti-EGFR cetuximab plus FOLFIRI improved overall survival in patients with metastatic colorectal cancer compared with bevacizumab plus FOLFIRI.

“These head-to-head trials suggest improved overall survival benefit with first-line use of anti-EGFR therapy relative to anti-VEGF therapy in combination with chemotherapy in patients with wild-type KRAS exon 2 metastatic colorectal cancer,” Schwartzberg and colleagues wrote. “Patients who are wild-type by extended RAS analysis seem more likely to benefit from anti-EGFR therapy.”

In this phase II analysis, the researchers randomly assigned 258 patients with wild-type KRAS exon 2 tumors to treatment with panitumumab plus mFOLFOX6 or bevacizumab plus mFOLFOX6. The primary endpoint was progression-free survival.

Only 278 patients received study treatment. Results showed that the progression-free survival was similar between the two treatment arms. The median progression-free survival was 10.9 for panitumumab and 10.1 months for bevacizumab. However, an overall survival analysis indicated that patients had prolonged survival with panitumumab compared with bevacizumab (34.2 months vs 24.3 months; P = .009). The researchers pointed out that the median overall survival seen for patients in both arms was longer than previously reported.

“In the phase III PRIME study, median overall survival of patients with wild-type KRAS exon 2 treated with panitumumab plus FOLFOX4 was 23.9 months,” the researchers wrote. “In the large NO16966 study in which patients were not selected by KRAS status, median overall survival was 21.3 months with bevacizumab and an oxaliplatin-containing regimen.”

Schwartzberg and colleagues also looked at treatment effects in patients with wild-type RAS that included exons 2, 3, and 4 of KRAS and NRAS.

In this group of patients, the median progression-free survival with panitumumab was 13 months compared with 9.5 months with bevacizumab (HR = .065; P = .029). Median overall survival was 41.3 months for panitumumab and 28.9 months for bevacizumab (P = .058).

According to the researchers, results of the phase III CALGB 80405 trial comparing chemotherapy with cetuximab or bevacizumab may provide further support for the hypothesis that anti-EGFR therapy provides improved overall survival in the first-line treatment of patients with wild-type KRAS metastatic colorectal cancer.