Reference Detail

Ref Type Journal Article
PMID (26341920)
Authors Peeters M, Oliner KS, Price TJ, Cervantes A, Sobrero AF, Ducreux M, Hotko Y, André T, Chan E, Lordick F, Punt CJ, Strickland AH, Wilson G, Ciuleanu TE, Roman L, Van Cutsem E, He P, Yu H, Koukakis R, Terwey JH, Jung AS, Sidhu R, Patterson SD
Title Analysis of KRAS/NRAS Mutations in a Phase III Study of Panitumumab with FOLFIRI Compared with FOLFIRI Alone as Second-line Treatment for Metastatic Colorectal Cancer.
Journal Clinical cancer research : an official journal of the American Association for Cancer Research
Vol 21
Issue 24
Date 2015 12 15
URL
Abstract Text We evaluated the influence of RAS mutation status on the treatment effect of panitumumab in a prospective-retrospective analysis of a randomized, multicenter phase III study of panitumumab plus fluorouracil, leucovorin, and irinotecan (FOLFIRI) versus FOLFIRI alone as second-line therapy in patients with metastatic colorectal cancer (mCRC; ClinicalTrials.gov, NCT0039183).Outcomes were from the study's primary analysis. RAS mutations beyond KRAS exon 2 (KRAS exons 3, 4; NRAS exons 2, 3, 4; BRAF exon 15) were detected by bidirectional Sanger sequencing in wild-type KRAS exon 2 tumor specimens. Progression-free survival (PFS) and overall survival (OS) were coprimary endpoints.The RAS ascertainment rate was 85%; 18% of wild-type KRAS exon 2 tumors harbored other RAS mutations. For PFS and OS, the hazard ratio (HR) for panitumumab plus FOLFIRI versus FOLFIRI alone more strongly favored panitumumab in the wild-type RAS population than in the wild-type KRAS exon 2 population [PFS HR, 0.70 (95% confidence interval [CI], 0.54-0.91); P = 0.007 vs. 0.73 (95% CI, 0.59-0.90); P = 0.004; OS HR, 0.81 (95% CI, 0.63-1.03); P = 0.08 vs. 0.85 (95% CI, 0.70-1.04); P = 0.12]. Patients with RAS mutations were unlikely to benefit from panitumumab. Among RAS wild-type patients, the objective response rate was 41% in the panitumumab-FOLFIRI group versus 10% in the FOLFIRI group.Patients with RAS mutations were unlikely to benefit from panitumumab-FOLFIRI and the benefit-risk of panitumumab-FOLFIRI was improved in the wild-type RAS population compared with the wild-type KRAS exon 2 population. These findings support RAS testing for patients with mCRC. Clin Cancer Res; 21(24); 5469-79. ©2015 AACR.See related commentary by Salazar and Ciardiello, p. 5415.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
KRAS G13X colorectal cancer no benefit Fluorouracil + Irinotecan + Oxaliplatin + Panitumumab Phase III Actionable In a Phase III clinical trial, the combination of Vectibix (panitumumab) and FOLFIRI did not have improved clinical benefit compared to FOLFIRI alone in patients with KRAS exon 2 mutant colorectal cancer (PMID: 26341920). 26341920
KRAS wild-type colorectal cancer sensitive Fluorouracil + Irinotecan + Oxaliplatin + Panitumumab Phase III Actionable In a Phase III clinical trial, the combination of Vectibix (panitumumab) and FOLFIRI improved progression-free survival and median overall survival in patients with RAS wild-type colorectal cancer compared to FOLFIRI treatment alone (PMID: 26341920). 26341920
KRAS wild-type colorectal cancer sensitive Fluorouracil + Irinotecan + Oxaliplatin + Panitumumab Phase III Actionable In a Phase III clinical trial, the combination of Vectibix (panitumumab) and FOLFIRI improved progression-free survival and median overall survival in patients with KRAS exon 2 wild-type colorectal cancer compared to FOLFIRI treatment alone, with an overall response rate of 35% (105/297) with the combination versus 10% (28/285) with FOLFIRI alone (PMID: 26341920). 26341920
KRAS mutant colorectal cancer no benefit Fluorouracil + Irinotecan + Oxaliplatin + Panitumumab Phase III Actionable In a Phase III clinical trial, the combination of Vectibix (panitumumab) and FOLFIRI did not have improved clinical benefit compared to FOLFIRI alone in colorectal cancer patients with KRAS mutations (PMID: 26341920). 26341920
KRAS G12X colorectal cancer no benefit Fluorouracil + Irinotecan + Oxaliplatin + Panitumumab Phase III Actionable In a Phase III clinical trial, the combination of Vectibix (panitumumab) and FOLFIRI did not have improved clinical benefit compared to FOLFIRI alone in patients with KRAS exon 2 mutant colorectal cancer (PMID: 26341920). 26341920
NRAS wild-type colorectal cancer predicted - sensitive Panitumumab Phase III Actionable In a Phase III clinical trial, the combination of Vectibix (panitumumab) and FOLFIRI improved progression-free survival and median overall survival in patients with RAS wild-type colorectal cancer compared to FOLFIRI treatment alone (PMID: 26341920). 26341920