Amgen has announced detailed results from the phase 3 ‘203’ trial evaluating Vectibix (panitumumab) administered in combination with FOLFOX (an oxaliplatin-based chemotherapy) as the first-line treatment of metastatic colorectal cancer (mCRC).
In the trial, Vectibix significantly improved median progression-free survival (PFS) by 1.6 months (9.6 versus 8.0 months for patients treated with FOLFOX alone, (hazard ratio 0.80; p=0.02)) in patients with KRAS wild-type mCRC (primary endpoint). The results were presented at the 2009 ECCO 15 – ESMO 34 European Multidisciplinary Congress in Berlin, Germany.
Further, the addition of Vectibix to chemotherapy also improved response rate in the KRAS wild-type patient population as measured by blinded central review (55% versus 48% in the FOLFOX only arm).
In patients with tumors harboring activating KRAS mutations, PFS was significantly inferior in the Vectibix arm. For patients with mutant KRAS tumors, median PFS was 7.3 months with Vectibix in combination with FOLFOX vs 8.8 months with FOLFOX alone (hazard ratio 1.29, p=0.02). These data confirm previous findings when oxaliplatin-based chemotherapy and an anti-epidermal growth factor receptor (EGFR) antibody are combined in patients bearing tumors with activating KRAS mutations.
Consistent with the PFS data, an interim analysis of overall survival, (a secondary endpoint) demonstrated a reduction in overall survival in patients with KRAS mutant tumors receiving Vectibix. The median overall survival for patients with KRAS wild-type mCRC has not yet been reached. Long-term follow-up for survival continues and the primary analysis is expected in the fourth quarter of 2009.
Originally designed to compare the treatment effect in the overall population, the study was amended to analyse outcomes with respect to the presence or absence of activating mutations in KRAS in the tumor itself. Tumor KRAS tests were finalised after the completion of enrollment and prior to the primary analysis.
Jean-Yves Douillard, director of clinical and translational research at medical oncology branch for Centre R Gauducheau, France and the principal investigator for the study, said: “I am very pleased with the outcome of this high quality trial which demonstrated that Vectibix improved progression-free survival and appeared to be well tolerated as a first-line metastatic colorectal cancer treatment in a selected patient population.
“This is the first prospective phase 3 data to demonstrate the importance of KRAS mutation as a predictive biomarker for Vectibix treatment in the first-line setting, providing definitive support for the use of the KRAS biomarker for selection of patients eligible for anti-EGFR therapy.”