Mixed results for the anti-EGFR panitumumab in KRAS exon 2 colorectal cancer

The experimental targeted agent panitumumab failed to improve progression-free survival over bevacizumab when added to first-line chemotherapy for wild-type KRAS exon 2 colorectal cancer, investigators reported online in the Journal of Clinical Oncology.

But patients treated with panitumumab lived a median of 10 months longer than those who received bevacizumab, said Dr. Lee Schwartzberg of West Clinic, Memphis, and his associates.

Panitumumab is an experimental monoclonal antibody that targets epidermal growth factor receptor (EGFR), while bevacizumab is an anti–vascular endothelial growth factor (anti-VEGF) antibody. The randomized, multicenter, phase II PEAK trial compared the agents head-to-head when added on to modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) for patients with previously untreated, unresectable wild-type KRAS exon 2 metastatic colorectal cancer. The investigators treated 278 patients with mFOLFOX6 plus biweekly panitumumab (6 mg/kg) or bevacizumab (5 mg/kg).

The primary endpoint, progression-free survival (PFS), was similar between treatment groups (10.9 vs. 10.1 months, respectively; hazard ratio, 0.87; 95% confidence interval, 0.65-1.17; P = .353), the investigators said. However, median overall survival (OS) was 10 months longer with panitumumab than bevacizumab (34.2 vs. 24.3 months; HR, 0.62; 95% CI, 0.44-0.89; P = .009), they reported (J. Clin. Oncol. 2014 March 31 [doi: 10.1200/jco.2013.53.2473]).

In an extended analysis of a wild-type RAS subgroup, PFS was 3.5 months longer for panitumumab (13.0 vs. 9.5 months for bevacizumab; HR, 0.65; 95% CI, 0.44-0.96; P = .029), the researchers reported. They added that patients experienced more skin toxicity and hypomagnesemia on panitumumab and more hypertension on bevacizumab.

Confounding could have caused the discrepancy between PFS and OS in the primary analysis, said Dr. Schwartzberg and his associates. "One possibility is that OS results were confounded by subsequent therapies. Alternatively, because the OS Kaplan-Meier curves separated before 6 months, PFS results may have been confounded by the negative contribution from the 23% of patients with RAS mutations beyond KRAS exon 2."

Nonetheless, they said, the OS benefit seen for panitumumab in the PEAK trial mirrors results for cetuximab, compared with bevacizumab, in the FIRE-3 trial. They added that the two head-to-head trials suggest that anti-EGFR therapy improves OS compared with antiangiogenesis therapy in this population, particularly in patients with wild-type RAS tumors.

Amgen sponsored the study and makes panitumumab (Vectibix). The investigators reported financial and advisory or consulting relationships with Amgen, Roche, and Merck, and three of them work for Amgen.

The experimental targeted agent panitumumab failed to improve progression-free survival over bevacizumab when added to first-line chemotherapy for wild-type KRAS exon 2 colorectal cancer, investigators reported online in the Journal of Clinical Oncology.

But patients treated with panitumumab lived a median of 10 months longer than those who received bevacizumab, said Dr. Lee Schwartzberg of West Clinic, Memphis, and his associates.

Panitumumab is an experimental monoclonal antibody that targets epidermal growth factor receptor (EGFR), while bevacizumab is an anti–vascular endothelial growth factor (anti-VEGF) antibody. The randomized, multicenter, phase II PEAK trial compared the agents head-to-head when added on to modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) for patients with previously untreated, unresectable wild-type KRAS exon 2 metastatic colorectal cancer. The investigators treated 278 patients with mFOLFOX6 plus biweekly panitumumab (6 mg/kg) or bevacizumab (5 mg/kg).

The primary endpoint, progression-free survival (PFS), was similar between treatment groups (10.9 vs. 10.1 months, respectively; hazard ratio, 0.87; 95% confidence interval, 0.65-1.17; P = .353), the investigators said. However, median overall survival (OS) was 10 months longer with panitumumab than bevacizumab (34.2 vs. 24.3 months; HR, 0.62; 95% CI, 0.44-0.89; P = .009), they reported (J. Clin. Oncol. 2014 March 31 [doi: 10.1200/jco.2013.53.2473]).

In an extended analysis of a wild-type RAS subgroup, PFS was 3.5 months longer for panitumumab (13.0 vs. 9.5 months for bevacizumab; HR, 0.65; 95% CI, 0.44-0.96; P = .029), the researchers reported. They added that patients experienced more skin toxicity and hypomagnesemia on panitumumab and more hypertension on bevacizumab.

Confounding could have caused the discrepancy between PFS and OS in the primary analysis, said Dr. Schwartzberg and his associates. "One possibility is that OS results were confounded by subsequent therapies. Alternatively, because the OS Kaplan-Meier curves separated before 6 months, PFS results may have been confounded by the negative contribution from the 23% of patients with RAS mutations beyond KRAS exon 2."

Nonetheless, they said, the OS benefit seen for panitumumab in the PEAK trial mirrors results for cetuximab, compared with bevacizumab, in the FIRE-3 trial. They added that the two head-to-head trials suggest that anti-EGFR therapy improves OS compared with antiangiogenesis therapy in this population, particularly in patients with wild-type RAS tumors.

Amgen sponsored the study and makes panitumumab (Vectibix). The investigators reported financial and advisory or consulting relationships with Amgen, Roche, and Merck, and three of them work for Amgen.

The experimental targeted agent panitumumab failed to improve progression-free survival over bevacizumab when added to first-line chemotherapy for wild-type KRAS exon 2 colorectal cancer, investigators reported online in the Journal of Clinical Oncology.

But patients treated with panitumumab lived a median of 10 months longer than those who received bevacizumab, said Dr. Lee Schwartzberg of West Clinic, Memphis, and his associates.

Panitumumab is an experimental monoclonal antibody that targets epidermal growth factor receptor (EGFR), while bevacizumab is an anti–vascular endothelial growth factor (anti-VEGF) antibody. The randomized, multicenter, phase II PEAK trial compared the agents head-to-head when added on to modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) for patients with previously untreated, unresectable wild-type KRAS exon 2 metastatic colorectal cancer. The investigators treated 278 patients with mFOLFOX6 plus biweekly panitumumab (6 mg/kg) or bevacizumab (5 mg/kg).

The primary endpoint, progression-free survival (PFS), was similar between treatment groups (10.9 vs. 10.1 months, respectively; hazard ratio, 0.87; 95% confidence interval, 0.65-1.17; P = .353), the investigators said. However, median overall survival (OS) was 10 months longer with panitumumab than bevacizumab (34.2 vs. 24.3 months; HR, 0.62; 95% CI, 0.44-0.89; P = .009), they reported (J. Clin. Oncol. 2014 March 31 [doi: 10.1200/jco.2013.53.2473]).

In an extended analysis of a wild-type RAS subgroup, PFS was 3.5 months longer for panitumumab (13.0 vs. 9.5 months for bevacizumab; HR, 0.65; 95% CI, 0.44-0.96; P = .029), the researchers reported. They added that patients experienced more skin toxicity and hypomagnesemia on panitumumab and more hypertension on bevacizumab.

Confounding could have caused the discrepancy between PFS and OS in the primary analysis, said Dr. Schwartzberg and his associates. "One possibility is that OS results were confounded by subsequent therapies. Alternatively, because the OS Kaplan-Meier curves separated before 6 months, PFS results may have been confounded by the negative contribution from the 23% of patients with RAS mutations beyond KRAS exon 2."

Nonetheless, they said, the OS benefit seen for panitumumab in the PEAK trial mirrors results for cetuximab, compared with bevacizumab, in the FIRE-3 trial. They added that the two head-to-head trials suggest that anti-EGFR therapy improves OS compared with antiangiogenesis therapy in this population, particularly in patients with wild-type RAS tumors.

Amgen sponsored the study and makes panitumumab (Vectibix). The investigators reported financial and advisory or consulting relationships with Amgen, Roche, and Merck, and three of them work for Amgen.