Similar Progression-Free Survival With Panitumumab vs Bevacizumab Plus Modified FOLFOX6 in Wild-Type KRAS Exon 2 Metastatic Colorectal Cancer
In a phase II trial (PEAK) reported in the Journal of Clinical Oncology, Schwartzberg et al compared the EGFR inhibitor panitumumab (Vectibix) vs the VEGF-A inhibitor bevacizumab (Avastin) combined with modified fluorouracil, leucovorin, and oxaliplatin (FOLFOX6) in patients with previously untreated wild-type KRAS exon 2 (codons 12 and 13) metastatic colorectal cancer. There was no significant difference between regimens in progression-free survival, the primary endpoint, although the panitumumab regimen was associated with better overall survival.
Study Details
In the trial, 285 patients with wild-type KRAS exon 2 unresectable metastatic colorectal cancer were randomly assigned to receive panitumumab 6 mg/kg (n = 142) or bevacizumab 5 mg/kg (n = 143) every 2 weeks plus modified FOLFOX6. The panitumumab and bevacizumab groups were generally balanced for age (median, 63 and 61 years), sex (61% and 67% male), Eastern Cooperative Oncology Group performance status (0 in 63% and 64%), primary tumor diagnosis (colon in 68% and 64%), number of metastatic sites (one in 37% and 39%, two in 35% and 34%, at least three in 27% and 26%), liver-only metastatic disease (26% and 27%), and median number of metastatic organs (three in both).
Similar Progression-Free Survival, Improved Overall Survival
Median progression-free survival was similar in the panitumumab vs bevacizumab group (10.9 vs 10.1 months, hazard ratio [HR] = 0.87, P = .353). Objective response rates were 57.8% (including three complete responses) vs 53.5% (including one complete response). Surgical resection was performed in 13% and 11% of patients, with complete resection in 10% and 8%. Post-study anti-EGFR monoclonal antibody therapy was given to 21% vs 38% of patients and subsequent anti-VEGF therapy to 40% vs 24%, with similar proportions of patients in the two groups receiving subsequent chemotherapy.
Overall survival outcomes were immature at the time of the primary analysis. Median overall survival was significantly longer in the panitumumab group (34.2 vs 24.3 months, HR = 0.62, P = .009).
Extended Wild-Type RAS Analysis
A prespecified secondary objective of the study was to assess treatment effects in an analysis of RAS that included exons 2, 3, and 4 of KRAS and NRAS. Among the 88 panitumumab patients and 82 bevacizumab patients with wild-type RAS, median progression-free survival was significantly longer in the panitumumab group (13.0 vs 9.5 months, HR = 0.65, P = .029), and there was a trend toward improved median overall survival with panitumumab (41.3 vs 28.9 months, HR = 0.63, P = .058).
Adverse events ≥ grade 3 occurred in 91% of patients in the panitumumab group vs 83% of patients in the bevacizumab group. Skin toxicity and hypomagnesemia were more common with panitumumab, and hypertension was more common with bevacizumab.
Fatal adverse events occurred during the treatment period in seven panitumumab patients (5%), including three considered related to study treatment (rectal perforation related to panitumumab, sepsis related to chemotherapy, and respiratory failure related to panitumumab and chemotherapy) and in nine bevacizumab patients (6%), including two considered related to study treatment (intestinal perforation and small intestinal perforation, both related to bevacizumab and chemotherapy). Grade 3 infusion reactions occurred in 7% vs 5% of patients. Adverse events led to treatment discontinuation in 24% vs 27% of patients.
The investigators concluded, “[Progression-free survival] was similar and [overall survival] was improved with panitumumab relative to bevacizumab when combined with [modified FOLFOX6] in patients with [wild-type] KRAS exon 2 tumors. Patients with [wild-type] RAS tumors seemed to experience more clinical benefit with anti-epidermal growth factor receptor therapy.”
Lee S. Schwartzberg, MD, of The West Clinic, Memphis, is the corresponding author for the Journal of Clinical Oncology article.
The study was sponsored by Amgen. For full disclosures of the study authors, visit jco.ascopubs.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
