Role of KRAS mutation in predicting response, progression-free survival, and overall survival in irinotecan-refractory patients treated with cetuximab plus irinotecan for a metastatic colorectal cancer: Analysis of 281 individual data from published series.

4035 Background: Cetuximab, a monoclonal antibody (mAb) directed against the epidermal growth factor receptor (EGFR), is approved in combination with irinotecan (Iri) for the treatment of Iri-refractory metastatic colorectal cancer (MCRC) expressing EGFR. Recent studies have shown that KRAS mutation (mut) confers resistance to anti-EGFR mAbs. We extracted data of 281 patients (pts) from 7 series (Lievre 2006 and 2008, Moroni 2005, Di Fiore 2007, De Roock 2007, Benvenuti 2007, Frattini 2007) to determine the role of KRAS mut in Iri-refractory MCRC patients treated with cetuximab plus Iri based-chemotherapy (CT).,The following data were collected: sex, age, previous CT lines, anti-EGFR regimen, response rate based on RECIST criteria, progression-free survival (PFS), overall survival (OS) and KRAS mutational status. Response rate was evaluated using the Fischer exact test. PFS and OS were calculated using the Kaplan-Meier method and compared with log-rank test. Predictive factors of response and survival were determined by logistic regression and Cox-regression model, respectively.,A total of 281 pts were included, 174 men and 107 women with a mean age of 59.8 yrs. Pts received a mean of 2.4 prior CT lines. 77 pts (27.4%) responded (3 complete response (CR) and 74 partial response (PR)), 107 (38.1%) had stable disease (SD) and 97 (34.5%) had disease progression (PD). A KRAS mut was detected in 98 pts including 40/107 (37.4%) pts with SD and 58/97 (59.8%) with PD. All responders were KRAS wild-type. KRAS mut was significantly associated with PD (p< 0.0001). Median PFS and OS were significantly lower in mutated KRAS pts, 12 weeks (wks) vs 24 wks (p<0.0001) and 36 wks vs 44 wks (p<0.0001), respectively. The absence of KRAS mut was identified as predictive factor of disease control (CR+PR+SD) (p<0.0001,OR:0.17;95IC:0.10-0.30) and OS (p<0.0001,OR:0.51;95IC:0.37-0.70), respectively.,KRAS mutational status plays a key role in response rate, PFS and OS in Iri-refractory MCRC pts treated with cetuximab and Iri. Our results demonstrate the potentially major impact of KRAS mutation in pts selection. [Table: see text].