Dataset Information

Clinical validation of the next-generation sequencing-based Extended RAS Panel assay using metastatic colorectal cancer patient samples from the phase 3 PRIME study.

ABSTRACT:

Purpose

To validate a next-generation sequencing (NGS)-based companion diagnostic using the MiSeqDx^® sequencing instrument to simultaneously detect 56 RAS mutations in DNA extracted from formalin-fixed paraffin-embedded metastatic colorectal cancer (mCRC) tumor samples from the PRIME study. The test's ability to identify patients with mCRC likely to benefit from panitumumab treatment was assessed.

Methods

Samples from PRIME, which compared first-line panitumumab?+?FOLFOX4 with FOLFOX4, were processed according to predefined criteria using a multiplex assay that included input DNA qualification, library preparation, sequencing, and the bioinformatics reporting pipeline. NGS mutational analysis of KRAS and NRAS exons 2, 3, and 4 was performed and compared with Sanger sequencing.

Results

In 441 samples, positive percent agreement of the Extended RAS Panel with Sanger sequencing was 98.7% and negative percent agreement was 97.6%. For clinical validation (n?=?528), progression-free survival (PFS) and overall survival (OS) were compared between patients with RAS mutations (RAS Positive) and those without (RAS Negative). Panitumumab?+?FOLFOX4 improved PFS in RAS Negative patients (P?=?0.02). Quantitative interaction testing indicated the treatment effect (measured by the hazard ratio of panitumumab?+?FOLFOX4 versus FOLFOX4) differed for RAS Negative versus RAS Positive for PFS (P?=?0.0038) and OS (P?=?0.0323).

Conclusions

NGS allows for broad, rapid, highly specific analyses of genomic regions. These results support use of the Extended RAS Panel as a companion diagnostic for selecting patients for panitumumab, and utilization is consistent with recent clinical guidelines regarding mCRC RAS testing. Overall, approximately 13% more patients were detected with the Extended RAS Panel versus KRAS exon 2 alone.

Clinical trial registry identifier

NCT00364013 (ClinicalTrials.gov).

SUBMITTER: Udar N

PROVIDER: S-EPMC6153611 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Publications

Clinical validation of the next-generation sequencing-based Extended RAS Panel assay using metastatic colorectal cancer patient samples from the phase 3 PRIME study.

Udar Nitin N Lofton-Day Catherine C Dong Jun J Vavrek Darcy D Jung A Scott AS Meier Kristen K Iyer Anita A Slaughter Ryan R Gutekunst Karen K Bach Bruce A BA Peeters Marc M Douillard Jean-Yves JY

Journal of cancer research and clinical oncology 20180717 10

<h4>Purpose</h4>To validate a next-generation sequencing (NGS)-based companion diagnostic using the MiSeqDx<sup>®</sup> sequencing instrument to simultaneously detect 56 RAS mutations in DNA extracted from formalin-fixed paraffin-embedded metastatic colorectal cancer (mCRC) tumor samples from the PRIME study. The test's ability to identify patients with mCRC likely to benefit from panitumumab treatment was assessed.<h4>Methods</h4>Samples from PRIME, which compared first-line panitumumab + FOLFO ...[more]

PMID: 30019318

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Dataset Information

Clinical validation of the next-generation sequencing-based Extended RAS Panel assay using metastatic colorectal cancer patient samples from the phase 3 PRIME study.

Purpose

Methods

Results

Conclusions

Clinical trial registry identifier

Publications

Clinical validation of the next-generation sequencing-based Extended RAS Panel assay using metastatic colorectal cancer patient samples from the phase 3 PRIME study.

Similar Datasets

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