P-0194 - KRAS genotype and the prevalent c.35 G > A mutation affect significantly worse prognosis of metastatic colorectal cancer (MCRC) patients fitting for...
|Date||28 June 2014|
|Event||World GI 2014|
|Citation||Annals of Oncology (2014) 25 (suppl_2): ii14-ii104. 10.1093/annonc/mdu165|
G. Bruera1, K. Cannita2, A. Tessitore3, A. Cortellini4, C. Sabourin Jean5, M. Tosi6, T. Frébourg6, E. Alesse3, C. Ficorella1, E. Ricevuto1
Bevacizumab (BEV) addiction to chemotherapy can predict increased efficacy in KRAS wild-type and mutant MCRC patients. Codon 12 KRAS mutations differentially affect GTPase function, and confer worse clinical behaviour. Prognostic relevance of KRAS genotype and the prevalent c.35 G > A mutation were verified in patients fit for, and after progression to first line FIr-B/FOx.
KRAS codon 12/13 mutations were screened. Activity and efficacy were evaluated and compared by log-rank.
Sixty-nine patients (45% overall MCRC) were treated with FIr-B/FOx: 32 KRAS wild-type, 17 c.35 G > A mutant, 20 other mutant. At median follow-up 24 months, objective response rate (ORR) was 77%, progression-free survival (PFS) 13 months, overall survival (OS) 31 months. Among wild-type and mutant patients, respectively: ORR 91% and 64%, PFS 14 and 11 months, OS 38 and 20 months. KRAS mutant patients showed a significantly worse OS compared to wild-type (P = 0.031). c.35 G > A mutant confirmed significantly worse OS compared to wild-type and to wild-type plus other mutant patients. Post-progression to FIr-B/FOx, among 46 second line treated patients (67%), at median follow-up 13 months, ORR was 36%, PFS 8 months, OS 14 months. Among patients treated with re-challenge of triplet chemotherapy plus targeted agent, and triplet regimens, respectively: ORR 83% and 29%, PFS 11 and 8 months, OS 40 and 11 months. OS was significantly different in patients treated with triplet chemotherapy plus targeted agent compared to other treatments, and to triplet regimens. Among wild-type and mutant patients, respectively: ORR 48% and 25%, PFS 9 and 8 months, OS 23 and 12 months. KRAS wild-type compared with mutant patients did not show significantly different OS, while it was significantly worse in c.35 G > A mutant patients.
KRAS mutant genotype and specifically the prevalent c.35 G > A mutation may significantly affect worse clinical outcome in patients fit for first line FIr-B/FOx intensive regimen. c.35 G > A mutation may also significantly affect worse OS after progression.