Novel Approach for Clinical Validation of the cobas KRAS Mutation Test in Advanced Colorectal Cancer
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ORIGINAL RESEARCH ARTICLE
Novel Approach for Clinical Validation of the cobas KRAS Mutation Test in Advanced Colorectal Cancer Abha Sharma1 • Guili Zhang1 • Shagufta Aslam1 • Karen Yu1 Melody Chee1 • John F. Palma1
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Ó The Author(s) 2016. This article is published with open access at Springerlink.com
Abstract Aim Our objective was to assess the performance of the cobas test versus comparators for KRAS mutation status and predicting clinical response to anti-epidermal growth factor receptor (EGFR) therapy in patients with metastatic colorectal cancer (mCRC). Methods mCRC samples from 398 patients from Roche study NO16968 (XELOXA) and 82 supplemental samples were tested with the cobasÒ KRAS mutation test (cobas test), the therascreenÒ KRAS RGQ PCR kit test (therascreen test), and Sanger sequencing as the reference method for detecting mutations in codons 12/13. Results For 461 eligible samples, the cobas test, therascreen test, and sequencing had invalid results for 5.2, 10.8, and 2.6 % of specimens, respectively. Valid cobas and therascreen test results had similar KRAS mutationpositive rates (37.3 vs. 36.3 %, respectively); sequencing was 28.5 %. Positive and negative percent agreement (PPA/NPA) between the cobas test and sequencing was 96.9 % (95 % confidence interval [CI] 92.2–98.8), and 88.7 % (95 % CI 84.7–91.8), respectively. PPA/NPA between the cobas and therascreen tests was 93.3 % (95 % CI 88.1–96.3) and 96.5 % (95 % CI 93.5–98.1), respectively. Bridging analysis from NCIC-CO.17 and NCT00113763 using the cobas test yielded modeled hazard ratios for overall survival and progression-free survival
Electronic supplementary material The online version of this article (doi:10.1007/s40291-016-0193-4) contains supplementary material, which is available to authorized users. & John F. Palma [email protected] 1
Medical Affairs Department, Roche Molecular Systems, 4300 Hacienda Drive, Pleasanton, CA 94588, USA
(PFS) of 0.558 (95 % CI 0.422–0.752) and 0.413 (95 % CI 0.304–0.550), respectively, for cetuximab and 0.989 (95 % CI 0.778–1.299) and 0.471 (95 % CI 0.360–0.626), respectively, for panitumumab, demonstrating significant efficacy in the KRAS-negative population for PFS. Conclusion The cobas test showed similar accuracy to the therascreen test for detecting KRAS mutations and could appropriately identify mCRC patients ineligible for anti-EGFR therapy as demonstrated by bridging analysis results.
Key Points Targeted therapy with cetuximab provides a survival benefit to patients with metastatic colorectal cancer (mCRC) whose tumors harbor a wild-type KRAS gene. To expand the available diagnostic options for testing the anti-epidermal growth factor receptor (EGFR) therapy response of patients with mCRC, the current study compared the performance of the cobas test with that of the therascreen test and Sanger sequencing. Bridging analysis of existing published data was performed through a method comparison study to validate clinical value. The cobas test demonstrated an analytical performance comparable to th
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