My ePortfolio Register   

RAS mutations linked to panitumumab clinical response in patients with metastatic colorectal cancer

Amgen announced the publication of a biomarker analysis of panitumumab in combination with FOLFOX, a type of oxaliplatin-based chemotherapy, for the first-line treatment of patients with metastatic colorectal cancer (mCRC).

Published in the New England Journal of Medicine, the analysis found that RAS mutations, beyond the known KRAS exon 2 mutations, predict lack of response to Vectibix in combination with FOLFOX.

RAS mutations are mutations occurring in exons 2, 3 and 4 of KRAS and NRAS.

“In recent years, we have made important progress in treating colorectal cancer with anti-EGFR (epidermal growth factor receptor) antibody therapies. Patients with KRAS exon 2 mutations, however, do not benefit from this treatment. Our latest findings now show that patients with mutations in other regions of KRAS -- exons 3 and 4 -- as well as those with mutations occurring in exons 3 and 4 of NRAS, do not benefit from treatment with panitumumab”, said Dr. Josep Tabernero, Head of the Medical Oncology Department at the Vall d'Hebron University Hospital, Director of the Vall d´Hebron Institute of Oncology (VHIO), and co-author of the study.

“This represents an important step in furthering our understanding of molecular cancer biology and more effectively tailoring anti-colorectal cancer therapies to individual patients”.

This predefined retrospective subset analysis of the PRIME (‘203) study assessed the safety and efficacy of Vectibix plus FOLFOX, compared to FOLFOX alone based on RAS or BRAF mutation status.

By more precisely narrowing the pool of patients treated with Vectibix plus FOLFOX to those with wild-type RAS, greater improvements in overall survival (OS) and progression-free survival (PFS) were observed. Specifically, previous data found that OS was improved by 4.4 months in patients with wild-type KRAS.

By further narrowing to patients with wild-type RAS, an improvement in OS of 5.8 months was observed.

In patients with wild-type RAS, OS was 26.0 months and 20.2 months (HR = 0.78; 95 percent CI, 0.62 - 0.99) and PFS was 10.1 months and 7.9 months (HR = 0.72, 95 percent CI, 0.58 - 0.90) in the Vectibix plus FOLFOX arm compared to the FOLFOX alone arm, respectively. BRAF mutations were not observed to have predictive value.

Conversely, in the patients with RAS mutations, inferior OS (HR = 1.25, 95 percent CI, 1.02-1.55) and PFS (HR = 1.34, 95 percent CI, 1.07-1.60) were observed in the Vectibix plus FOLFOX arm compared to the FOLFOX alone arm. Amgen has informed investigators and physicians of this important new safety information, and is working with regulatory agencies regarding appropriate communication of the outcomes of the analysis.

 

Source: VHIO

0

Comments

Please click on the 'New Comment' link to the left to add a new comment, or alternatively click any 'Add Comment' link next to any existing post to respond. The views expressed here are not those of ecancer. For more information please view our Privacy Policy.



Founding partners

European Cancer Organisation European Institute of Oncology

Founding Charities

Foundazione Umberto Veronesi Fondazione IEO Swiss Bridge

Published by

Cancer Intelligence