The supplemental Biologics License Application for panitumumab has been approved by the FDA 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 (mCRC) 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-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. This companion diagnostic helps physicians identify patients who 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 mCRC patients," said Marwan G. Fakih, MD, Co-Director of the Gastrointestinal Cancer Program at City of Hope, Duarte, Calif. "Panitumumab has demonstrated a significant overall survival benefit to patients whose mCRC 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."
The full approval for panitumumab as a treatment for patients with wild-type KRAS mCRC 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 mCRC was based on a retrospective analysis from the PRIME study and prospective, pre-defined analyses from the phase III '0007 study. This research evaluated the efficacy of panitumumab plus best supportive care (BSC) versus BSC alone in patients with chemorefractory, wild-type KRAS mCRC. Data from a key secondary endpoint showed that patients with wild-type RAS (exons 2, 3, and 4 of KRAS and NRAS) mCRC treated with panitumumab plus BSC resulted in a statistically significant improvement in overall survival of 10 months compared to 6.9 months for patients treated with BSC alone (HR=0.70; 95% CI: 0.53, 0.93, p=0.0135). The safety profile of panitumumab in patients with wild-type RAS mCRC is consistent with that seen previously in patients with wild-type KRAS mCRC.
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.