FDA Approves Panitumumab for Use in Wild-Type RAS Metastatic Colorectal Cancer

Today, the U.S. Food and Drug Administration (FDA) approved the supplemental Biologics License Application (sBLA) for panitumumab (Vectibix) for patients with wild-type RAS (defined as wild-type in both KRAS and NRAS as determined by an FDA-approved test for this use) metastatic colorectal cancer as first-line therapy in combination with FOLFOX and as monotherapy following disease progression after prior treatment with fluoropyrimidine, oxaliplatin, and irinotecan-containing chemotherapy. Panitumumab is the first and only fully human monoclonal anti–epidermal growth factor receptor (EGFR) antibody approved by the FDA for this patient population.

As part of this new indication, the FDA approved the first multigene, next-generation sequencing-based test to identify the RAS mutation status of a patient's tumor. Next-generation sequencing is a novel diagnostics test technique that makes a more personalized medicine approach possible. This companion diagnostic helps physicians identify patients that are more likely to benefit from treatment with panitumumab.

“Of the few biomarkers in colorectal cancer, RAS mutation status provides actionable information when deciding on a first-line treatment option in metastatic colorectal cancer patients,” said Marwan G. Fakih, MD, Codirector of the Gastrointestinal Cancer Program at City of Hope in Duarte, California. “Panitumumab has demonstrated a significant overall survival benefit to patients whose metastatic colorectal cancer does not have mutations in RAS, providing physicians with a novel targeted treatment option and allowing us to develop a personalized approach as we help patients fight this devastating disease.”

Approval Based on Phase III Trials

The full approval for panitumumab as a treatment for patients with wild-type KRAS metastatic colorectal cancer was based on results from the phase III PRIME and ASPECCT trials. The approval of a refined indication for the treatment of patients with wild-type RAS metastatic colorectal cancer was based on a retrospective analysis from the PRIME study and prospective, predefined analyses from the phase III '0007 study.

The '0007 study evaluated the efficacy of panitumumab plus best supportive care vs best supportive care alone in patients with chemorefractory, wild-type KRAS metastatic colorectal cancer. Data from a key secondary endpoint showed that patients with wild-type RAS (exons 2, 3, and 4 of KRAS and NRAS) metastatic colorectal cancer treated with panitumumab plus best supportive care resulted in a statistically significant improvement in overall survival of 10 months compared to 6.9 months for patients treated with best supportive care alone (hazard ratio = 0.70; 95% confidence interval = 0.53–0.93, P = .0135).

The safety profile of panitumumab in patients with wild-type RAS metastatic colorectal cancer is consistent with that seen previously in patients with wild-type KRAS metastatic colorectal cancer.

Most common adverse reactions (≥ 20%) of panitumumab as monotherapy are skin rash with variable presentations, paronychia, fatigue, nausea, and diarrhea. Most common adverse reactions (≥ 20%) with panitumumab plus FOLFOX are diarrhea, stomatitis, mucosal inflammation, asthenia, paronychia, anorexia, hypomagnesemia, hypokalemia, rash, acneiform dermatitis, pruritus, and dry skin. The most common serious adverse reactions (≥ 2%difference between treatment arms) were diarrhea and dehydration. 

“This approval for panitumumab reinforces the significance of biomarker testing as a treatment planning tool in metastatic colorectal cancer, and further validates the potential for precision medicine to optimize patient outcomes,” said Sean E. Harper, MD, Executive Vice President of Research and Development at Amgen.

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®.


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