Cetuximab plus FOLFIRI: Final data from the CRYSTAL study on the association of KRAS and BRAF biomarker status with treatment outcome

Abstract

Background: The phase III CRYSTAL study showed that patients (pts) with KRAS wild-type (wt) tumors benefit from the addition of cetuximab to FOLFIRI as first-line treatment for metastatic colorectal cancer (mCRC). BRAF is a downstream effector of KRAS. Method(s): Tumor KRAS and BRAF mutation status (wt or mutant [mt]) was determined for an expanded patient population using polymerase chain reaction and melting curve assays. Treatment arms were compared according to mutation status (log rank and Cochran-Mantel-Haenszel tests). Result(s): Of 1,198 pts in the primary analysis population, 1,063 (89%) were evaluable for KRAS mutation status; double the previous ascertainment rate. In pts with KRAS wt tumors, all efficacy endpoints were significantly improved in pts receiving cetuximab + FOLFIRI compared with FOLFIRI alone. Tumor BRAF status was evaluable in 625/666 pts with KRAS wt tumors. BRAF mutation was a marker of poor prognosis in both treatment arms (see Table). Conclusion(s): For all efficacy endpoints, including survival, this analysis confirms the value of KRAS mutational status as a predictor of treatment outcome in pts with mCRC receiving cetuximab plus FOLFIRI first-line. BRAF mutation status does not appear to be a strong predictive biomarker for the addition of cetuximab to FOLFIRI but the sample size may be too small to be conclusive.(Table presented).