BERLIN—Panitumumab (Vectibix), in combination with FOLFIRI as second-line treatment, significantly improved progression-free survival compared to FOLFIRI alone in patients with KRAS wild-type metastatic colorectal cancer, according to study results that will be presented at ESMO 2009 (see Table). However median overall survival did not achieve statistical significance in the study arm.
The multicenter, randomized, phase III trial (study 181) by Amgen involved 1,186 patients who received either 6.0 mg/kg of panitumumab and FOLFIRI every two weeks or FOLFIRI alone. The primary endpoints were progression-free survival (PFS) and overall survival (OS); secondary endpoints were objective response rate, time-to-progression, duration of response, and safety by KRAS status. The adverse events included skin toxicity, diarrhea, and hypomagnesemia.
The addition of Vectibix had no positive or negative effect on PFS or OS in patients with tumors harboring activating KRAS mutations, Amgen reported.
“With these data, Vectibix has now demonstrated improved progression-free survival in phase III trials in patients with KRAS wild-type tumors in both first- and second-line treatment of metastatic colorectal cancer,” said Roger M. Perlmutter, MD, PhD, executive vice president of research and development at Amgen. “These results add to the growing body of evidence confirming the utility of KRAS as a predictive biomarker.”
Originally designed to compare the treatment effect in the overall population, the study was amended to analyze outcomes with respect to the presence or absence of activating mutations in KRAS in the tumor itself. Tumor KRAS status was ascertained in more than 90% of patients enrolled in this trial.
Amgen also announced phase III results from a first-line trial (study 203) that showed panitumumab significantly improved PFS in metastatic colorectal cancer patients with KRAS wild-type tumors in combination with FOLFOX.