Sean E. Harper, MD
Patients with chemorefractory KRAS
wild-type metastatic colorectal cancer (mCRC) had a statistically significant improvement in overall survival (OS) when treated with panitumumab (Vectibix) versus best supportive care, according to data released from a phase IIl study. OS was also improved in patients with wild-type RAS
tumors, a secondary endpoint, defined as those without alterations in exons 2, 3, and 4 of KRAS
Amgen, the developer of the drug, has submitted complete data from the analysis for presentation at an upcoming medical conference and for publication.
"These positive overall survival results for Vectibix reinforce the importance of KRAS and RAS biomarkers in making treatment decisions in metastatic colorectal cancer," Sean E. Harper, MD, executive vice president of Research and Development at Amgen, said in a statement.
In the phase III open-label study, patients received panitumumab at 6 mg/kg every 14 days. The investigator determined best supportive care. The primary endpoint of the study was OS, with secondary outcomes focused on progression-free survival (PFS), safety, and response. Amgen has not yet released data from the study.
Panitumumab was initially approved as a treatment for patients with mCRC in September 2006. Since that time, the label has undergone various revisions and changes, along with approvals for new indications.
In May 2014, the FDA approved panitumumab in combination with FOLFOX as a frontline treatment for patients with KRAS
wild-type mCRC along with a companion diagnostic. This approval was based on findings from two phase III clinical trials. In the first study, labeled PRIME, first-line panitumumab plus FOLFOX4 improved PFS by 1.6 months and OS by 4.4 months compared with FOLFOX4 alone in untreated patients with KRAS
wild-type mCRC. In the second trial, known as ASPECCT, median OS with single-agent panitumumab was found to be noninferior to cetuximab (Erbitux) in previously treated patients with KRAS
Based on data from these trials, the initial accelerated approval granted in 2006 was transitioned to a full approval for panitumumab as a treatment for patients with KRAS wild-type mCRC.
“Vectibix is now the first approved biologic to show a significant survival benefit when combined with FOLFOX as a first-line treatment,” Lee S. Schwartzberg, MD, medical director of The West Clinic in Memphis, Tennessee, said in a press release at the time of the approval in 2014. “Vectibix has shown a significant benefit to patients with wild-type KRAS metastatic colorectal cancer when used with FOLFOX, which gives us a valuable new treatment option as we help patients fight this devastating disease.”
In early March 2015, the FDA revised the panitumumab label further to be specifically indicated for the treatment of patients with RAS
wild-type mCRC, as opposed to KRAS
alone. This change further solidified a continued shift toward an expanded testing strategy.
The updated label was preceded by a change to NCCN guidelines indicating that cetuximab and panitumumab should only be utilized in patients with KRAS/NRAS
wild-type mCRC. In a biomarker analysis of the phase III PRIME study that was published in the New England Journal of Medicine
, narrowing down treatment with panitumumab to patients with only RAS
wild-type mutations resulted in an improvement in OS of 5.8 months.
The median OS with panitumumab plus FOLFOX was 26.0 months compared with 20.2 months with FOLFOX alone in patients with wild-type RAS
mCRC (HR = 0.78; P
= .04). Moreover, this study demonstrated that patients with RAS
mutations had a 3.6-month worse median OS with panitumumab compared with FOLFOX alone (15.6 vs 19.2 months; HR = 1.25; P