PRIME Trial Offers More Good News for Panitumumab in Metastatic Colorectal Cancer

Preliminary data from a phase 3 study show that panitumumab (Vectibix) added to standard FOLFOX chemotherapy as a first-line treatment for metastatic colorectal cancer significantly improves PFS in patients with wild-type KRAS.

Preliminary data from a phase III study show that panitumumab (Vectibix) added to standard FOLFOX chemotherapy as a first-line treatment for metastatic colorectal cancer (mCRC) significantly improves progression-free survival (PFS) in patients with wild-type KRAS. Results suggest that panitumumab might someday be another option for patients concerned about the adverse effects and administration of other biopharmaceuticals approved in this setting.

The PRIME (Panitumumab Randomized Trial in Combination with Chemotherapy for Metastatic Colorectal Cancer to Determine Efficacy) study randomized 1183 patients to receive FOLFOX4 every 2 weeks with or without 6.0 mg/kg of panitumumab. KRAS status was identified after enrollment but prior to treatment, and David Reese, MD, executive medical director, Global Development, who heads the Vectibix program at Amgen, said 60% of patients had wild-type KRAS. For these patients, median PFS was 1.6 months longer in the panitumumab group than in the chemotherapy-alone group, at 9.6 versus 8.0 months, respectively (P = .02), a significant result. Blinded central review determined that 55% of patients with wild-type KRAS responded to treatment in the combination group compared with 48% of wild-type KRAS patients in the FOLFOX-only group. Median overall survival (OS) was 18.8 months in the group that received only FOLFOX and has not yet been reached in the panitumumab-combination arm. Results with panitumumab were, as expected, inferior in patients with KRAS mutations; the drug’s recently revised label advises against using panitumumab in this patient population. Adverse events were as expected, with more patients in the panitumumab cohort reporting events typically associated with EGFR inhibitors, such as rash, diarrhea, and hypomagnesemia.

Jean-Yves Douillard, director of Clinical and Translational Research, Medical Oncology Branch, Centre R Gauducheau in France led the PRIME study and presented data at the Presidential Session of the ECCO 15 - ESMO 34 Joint Congress. “I am very pleased with the outcome of this high quality trial which demonstrated that Vectibix improved PFS and appeared to be well tolerated as a first-line mCRC treatment in a selected patient population,” he said. Final data are expected by the end of the year.

In an Amgen investor meeting following the Presidential Session, Dr Douillard was asked about the importance of assessing KRAS status in patients with mCRC. “It is worth getting the KRAS mutation as soon as we can,” he said. “KRAS occurs very early in the carcinogenesis of colon cancer,” he added, noting that it is evident in the primary tumor, making it easy to determine after resection. Dr Douillard also compared the PRIME results to a recent retrospective trial examining bevacizumab (Avastin) with chemotherapy as a first-line treatment for mCRC. He said an indirect comparison suggests similar outcomes for median OS, median PFS, and response are similar, so physicians and patients should consider the toxicity profile for both agents and the ease of administration when making treatment decisions.

Data were reported earlier this week on the 181 trial, which evaluated second-line therapy with panitumumab plus a FOLFIRI chemotherapy regimen in patients with mCRC. Results were encouraging for patients with wild-type KRAS but poor for those with KRAS mutations. Other studies with panitumumab are ongoing, including one in metastatic head and neck cancer, and Amgen expects to release these results next year.