Heinz-Josef Lenz1, Fang-Shu Ou2, Alan P Venook3, Howard S Hochster4, Donna Niedzwiecki5, Richard M Goldberg6, Robert J Mayer7, Monica M Bertagnolli8, Charles D Blanke9, Tyler Zemla2, Xueping Qu10, Pratyaksha Wirapati11, Sabine Tejpar12, Federico Innocenti13, Omar Kabbarah10. 1. 1University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA. 2. Mayo Clinic Cancer Center, Rochester, MN. 3. 3University of California, San Francisco, San Francisco, CA. 4. 4Yale Cancer Center, New Haven, CT. 5. 5Duke University Medical Center, Durham, NC. 6. 6West Virginia University Cancer Institute, Morgantown, WV. 7. 7Dana-Farber Cancer Institute, Boston, MA. 8. 8Brigham and Women's Hospital, Boston, MA. 9. 9Oregon Health & Science University, Portland, OR. 10. 10Genentech, San Francisco, CA. 11. 11Swiss Institute of Bioinformatics, Lausanne, Switzerland. 12. 12Universitair Ziekenhuis Leuven, Leuven, Belgium. 13. 13The University of North Carolina at Chapel Hill, Chapel Hill, NC.
Abstract
PURPOSE: To determine the predictive and prognostic value of the consensus molecular subtypes (CMSs) of colorectal cancer (CRC) that represent a merging of gene expression-based features largely in primary tumors from six independent classification systems and provide a framework for capturing the intrinsic heterogeneity of CRC in patients enrolled in CALGB/SWOG 80405. PATIENTS AND METHODS: CALGB/SWOG 80405 is a phase III trial that compared the addition of bevacizumab or cetuximab to infusional fluorouracil, leucovorin, and oxaliplatin or fluorouracil, leucovorin, and irinotecan as first-line treatment of advanced CRC. We characterized the CMS classification using a novel NanoString gene expression panel on primary CRCs from 581 patients enrolled in this study to assess the prognostic and predictive value of CMSs in these patients. RESULTS: The CMSs are highly prognostic for overall survival (OS; P < .001) and progression-free survival (PFS; P < .001). Furthermore, CMSs were predictive for both OS (P for interaction < .001) and PFS (P for interaction = .0032). In the CMS1 cohort, patients treated with bevacizumab had a significantly longer OS than those treated with cetuximab (P < .001). In the CMS2 cohort, patients treated with cetuximab had a significantly longer OS than patients treated with bevacizumab (P = .0046). CONCLUSION: These findings highlight the possible clinical utility of CMSs and suggests that refinement of the CMS classification may provide a path toward identifying patients with metastatic CRC who are most likely to benefit from specific targeted therapy as part of the initial treatment.
PURPOSE: To determine the predictive and prognostic value of the consensus molecular subtypes (CMSs) of colorectal cancer (CRC) that represent a merging of gene expression-based features largely in primary tumors from six independent classification systems and provide a framework for capturing the intrinsic heterogeneity of CRC in patients enrolled in CALGB/SWOG 80405. PATIENTS AND METHODS: CALGB/SWOG 80405 is a phase III trial that compared the addition of bevacizumab or cetuximab to infusional fluorouracil, leucovorin, and oxaliplatin or fluorouracil, leucovorin, and irinotecan as first-line treatment of advanced CRC. We characterized the CMS classification using a novel NanoString gene expression panel on primary CRCs from 581 patients enrolled in this study to assess the prognostic and predictive value of CMSs in these patients. RESULTS: The CMSs are highly prognostic for overall survival (OS; P < .001) and progression-free survival (PFS; P < .001). Furthermore, CMSs were predictive for both OS (P for interaction < .001) and PFS (P for interaction = .0032). In the CMS1 cohort, patients treated with bevacizumab had a significantly longer OS than those treated with cetuximab (P < .001). In the CMS2 cohort, patients treated with cetuximab had a significantly longer OS than patients treated with bevacizumab (P = .0046). CONCLUSION: These findings highlight the possible clinical utility of CMSs and suggests that refinement of the CMS classification may provide a path toward identifying patients with metastatic CRC who are most likely to benefit from specific targeted therapy as part of the initial treatment.
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