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New Analyses Identify Predictive Biomarkers For Vectibix® (Panitumumab) In Patients With Metastatic Colorectal Cancer

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Amgen (NASDAQ: AMGN) recently announced results from three analyses of Vectibix® (panitumumab) in combination with FOLFOX, an oxaliplatin-based chemotherapy regimen, as a first-line treatment for metastatic colorectal cancer (mCRC). These analyses include the description of new predictive biomarkers of clinical response to Vectibix, activating mutations in KRAS (beyond exon 2) and mutations in NRAS, collectively referred to as RAS.

“Amgen helped establish KRAS gene mutation as a biomarker for lack of response to anti-EGFR treatment,” said Sean E. Harper , M.D., executive vice president of Research and Development at Amgen. “The identification of new biomarkers may further help to identify appropriate patients with this incurable disease for such treatment.”

The RAS biomarkers were identified in a predefined retrospective subset analysis of the PRIME trial, where RAS was defined as exons 2, 3 and 4 of KRAS and NRAS. Mutational status of tumors was determined by Sanger sequencing in parallel with WAVE®-based SURVEYOR® Scan Kits (CRC RAScan™) from Transgenomic, Inc. (TBIO). In this exploratory analysis, patients with wild-type RAS mCRC who were administered Vectibix in combination with FOLFOX demonstrated an improvement in median overall survival (OS) of 26.0 months compared to 20.2 months for patients treated with FOLFOX alone (HR = 0.78, 95 percent CI, 0.62-0.99).

Patients with mutant RAS tumor status had inferior progression-free survival (PFS) (HR = 1.34, 95 percent CI, 1.07-1.60) and OS (HR = 1.25, 95 percent CI, 1.02-1.55) when administered Vectibix in combination with FOLFOX chemotherapy versus FOLFOX alone. These results suggest that RAS mutation status beyond KRAS may be predictive of negative outcomes in patients receiving Vectibix plus FOLFOX in mCRC. Amgen is working to inform investigators and physicians of this important new safety information, as well as working with regulatory agencies regarding appropriate communication of the outcomes of this analysis.

Results of this study will be presented at the 2013 American Society of Clinical Oncology (ASCO) Annual Meeting on Tuesday, June 4, 8:00 a.m. – 12:00 p.m. CDT, S405 (Abstract No. 3511; Poster Discussion).

In a separate and updated exploratory analysis of longer follow-up of OS of the PRIME trial (primary endpoint of PFS), an improvement in OS was observed in patients with wild-type KRAS exon 2 mCRC treated with Vectibix in combination with FOLFOX. Median OS was 23.8 months compared to 19.4 months for patients treated with FOLFOX alone (HR = 0.83, 95 percent CI, 0.70-0.98). In both PRIME analyses, the most commonly reported adverse events for the Vectibix treatment arms included rash, hypomagnesemia and diarrhea. The adverse event profiles for the wild-type tumor and mutant tumor populations were similar.

Updated results of the study will be presented at the 2013 ASCO Annual Meeting on Sunday, June 2, 8:00 a.m. – 11:45 a.m. CDT, S Hall A2 (Abstract No. 3620; Poster).
In a separate predefined secondary objective subset analysis of the PEAK study, patients with wild-type RAS mCRC treated with Vectibix in combination with FOLFOX had a median PFS of 13.1 months compared to 9.5 months (HR = 0.63, 95 percent CI, 0.43-0.94) for patients treated with bevacizumab in combination with FOLFOX. Median OS was not reached in the Vectibix arm, but the OS HR favored the Vectibix arm (HR = 0.55, 95 percent CI, 0.33-1.01). The most commonly reported adverse events for the Vectibix treatment arm included rash, hypomagnesemia and dehydration. The adverse event profiles for the wild-type tumor and mutant tumor populations were similar. No new toxicities were identified for Vectibix.

Updated results of the study will be presented at the 2013 ASCO Annual Meeting on Sunday, June 2, 8:00 a.m. – 11:45 a.m. CDT, S Hall A2 (Abstract No. 3631; Poster).

Source: PR Newswire