In First-Line Metastatic CRC, Outcomes Comparable for Panitumumab and Bevacizumab

Audrey Andrews

February 2013, Vol 4, No 2 - GI Cancers Symposium

San Francisco, CA—A randomized phase 2 study that compared panitu­mumab (Vectibix) and bevacizumab (Avastin) in the first-line treatment of metastatic colorectal cancer (CRC) showed these drugs to be similar in terms of progression-free survival (PFS) and overall survival (OS) benefits.

Although bevacizumab is approved by the US Food and Drug Admin­istration for the first-line treatment of patients with metastatic CRC and wild-type KRAS status, panitumumab is not. The phase 2 PEAK study compared the drugs in 285 metastatic un­resectable patients, in conjunction with modified FOLFOX6 given every 2 weeks.

“To our knowledge, this is the first study comparing an anti-EGFR [epidermal growth factor receptor] agent to bevacizumab in combination with an oxaliplatin-based regimen in KRAS wild-type patients with metastatic colorectal cancer,” said Lee Schwartzberg, MD, FACP, Medical Director, The West Clinic, Memphis and Chief of the Division of Hematology/Oncology, The Uni­versity of Tennessee, Memphis.

The median PFS was 10.9 months with panitumumab and 10.1 months with bevacizumab (hazard ratio [HR], 0.87; P = .35). Median OS has not been reached with panitumumab and was 25.4 months with bevacizumab (HR, 0.72; P = .14).

Dr Schwartzberg noted that while follow-up is short, the OS curves are separating, which suggests that a difference could emerge with time, “although it’s still very early. We will be updating this in the near future.”

The overall response rates were 82% with panitumumab and 76% with beva­cizumab, and the resection rates were 13% and 11%, respectively. The treatment exposure to the individual agents and the number of cycles received were the same between the arms.

In the subgroup analysis of treatment HRs, no clear differences were shown, although for PFS, panitumu­mab was favored for patients with ≥3 metastatic sites (HR, 0.52). For OS, patients who were young, with a high tumor burden and with high levels of lactate dehydrogenase (factors often seen in the same patients, he pointed out), fared better with panitumumab as well, he noted.

These differences were “hypothesis-generating only,” Dr Schwartzberg emphasized.

The drugs were equally well tolerated, and no new safety signals were observed. “The safety profile in both treatment arms was similar to previous reported studies, and the treatment discontinuation rates due to adverse events [AEs] were similar between the arms,” Dr Schwartzberg said. He noted that although the side effect profiles were different for the 2 drugs, the percentage of AEs was not.

Grades 3 and 4 AEs were noted in 86% of the patients receiving panitumumab plus modified FOLFOX6 and in 76% of the patients receiving bevacizumab plus modified FOLFOX6; AEs leading to permanent discontinuation of the drug occurred in 24% and 27% of the patients, respectively.
Dr Schwartzberg maintained that as a result of these findings he would consider panitumumab to be as effective as bevacizumab in the first-line setting for KRAS wild-type metastatic CRC, and he would feel “comfortable” using it.