FDA Approves First-Line Panitumumab for RAS Wild-Type mCRC

Marwan G. Fakih, MD

The FDA has approved panitumumab (Vectibix) in combination with FOLFOX as a frontline treatment for patients with RAS wild-type metastatic colorectal cancer (mCRC), according to Amgen, the company marketing the anti-EGFR antibody.

In addition to the frontline approval, the agency also cleared panitumumab as a monotherapy for RAS wild-type mCRC following prior treatment with fluoropyrimidine, oxaliplatin, and irinotecan-containing chemotherapy. For the determination of RAS status (specifically exons 2, 3, and 4 of KRAS and NRAS), the FDA also approved a multigene, next-generation sequencing-based companion diagnostic.

The expanded RAS indication was based on an improvement in overall survival (OS) in the prospective phase III 20100007 study and in a retrospective biomarker analysis of the phase III PRIME study. The addition of panitumumab to FOLFOX improved OS by 5.6 months for untreated patients with mCRC in the PRIME study. Additionally, panitumumab improved OS by 3.1 months versus best supportive care in the 20100007 study for patients with chemorefractory RAS wild-type mCRC.

"Of the few biomarkers in colorectal cancer, RAS mutation status provides actionable information when deciding on a first-line treatment option in mCRC patients," Marwan G. Fakih, MD, co-director of the Gastrointestinal Cancer Program at City of Hope, said in a statement. "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."

In the open-label 20100007 study, 377 patients were randomized in a 1:1 ratio to receive 6 mg/kg of panitumumab every 2 weeks plus best supportive care (n = 189) or best supportive care alone (n = 188). All patients in the study had progressed or were intolerant to prior treatment with irinotecan and oxaliplatin. Additionally, patients had received prior treatment with a thymidylate synthase inhibitor.

The median OS was 10.0 months with panitumumab versus 6.9 months with best supportive care alone for those with RAS wild-type mCRC (HR, 0.70; 95% CI, 0.53-0.93; P = .0135). In those with wild-type KRAS mCRC, median OS was 10.0 months in the panitumumab arm compared with 7.4 months with best supportive care alone (HR, 0.73; 95% CI, 0.57-0.93; P = .0096).

In those with RAS wild-type mCRC, the median PFS was 5.2 months with panitumumab versus 1.7 months with supportive care (HR, 0.46; 95% CI, 0.35-0.59; P <.0001). The ORR with panitumumab was 31% compared with 2.3% with supportive care (odds ratio, 20.0; 95% CI, 5.9-101.6; P <.0001).

In a biomarker analysis of the phase III PRIME study, the median OS with panitumumab plus FOLFOX was 25.8 months compared with 20.2 months with FOLFOX alone in patients with wild-type RAS mCRC (HR, 0.77; 95% CI, 0.64-0.94). The median PFS was 10.1 months with panitumumab versus 7.9 months for FOLFOX alone (HR, 0.72; 95% CI, 0.58-0.90).

Across the full 1183-patient PRIME study for those with broader KRAS wild-type mCRC, panitumumab plus FOLFOX showed a median OS of 23.8 months compared with 19.4 months for FOLFOX alone (HR, 0.82, 95% CI, 0.70-0.98). The combination had a median PFS of 9.6 months compared with 8.0 months with FOLFOX alone (HR, 0.80; 95% CI, 0.66-0.97; P = .02).

In addition to the RAS indications, panitumumab also received a full approval from the FDA as a treatment for patients with KRAS wild-type mCRC. This indication was based on the full analysis of the PRIME study along with the ASPECCT trial, a phase III noninferiority trial comparing single-agent panitumumab with standard of care cetuximab (Erbitux) for patients with chemorefractory KRAS wild-type mCRC. In this study, panitumumab showed an OS of 10.4 months compared with 10.0 months for cetuximab, meeting the criteria for noninferiority (HR, 0.97; 95% CI, 0.84-1.11).

"Every patient with cancer is unique, and we are committed to utilizing cutting-edge science and technology to target treatments to the patients more likely to benefit," Sean E. Harper, MD, executive vice president of Research and Development at Amgen, said in a statement. "This approval for Vectibix 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."