Impact of Consensus Molecular Subtype on Survival in Patients With Metastatic Colorectal Cancer: Results From CALGB/SWOG 80405 (Alliance)
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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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- Authors
- Lenz, H.-J., Ou, F.-S., Venook, A. P., Hochster, H. S., Niedzwiecki, D., Goldberg, R. M., Mayer, R. J., Bertagnolli, M. M., Blanke, C. D., Zemla, T., Qu, X., Wirapati, P., Tejpar, S., Innocenti, F., & Kabbarah, O.
- Affiliations
- USC Norris Comprehensive Cancer Center (US)
- Mayo Clinic (US)
- University of California, San Francisco (US)
- Yale Cancer Center, New Haven, CT
- Duke Medical Center (US)
- West Virginia University (US)
- Dana-Farber Cancer Institute (US)
- Brigham and Women's Hospital (US)
- Oregon Health & Science University (US)
- Genentech (US)
- SIB Swiss Institute of Bioinformatics (CH)
- Universitair Ziekenhuis Leuven (BE)
- University of North Carolina at Chapel Hill (US)
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2019-08-01
- Volume
- 37
- Issue
- 22
- Pages
- 1876-1885
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- PMC
- PMC6675593
- OpenAlex
- W2943196840
- Cited by
- 246
- References
- 35
- Citations by year
- 2026: 11 · 2025: 31 · 2024: 28 · 2023: 27 · 2022: 39 · 2021: 61 · 2020: 37 · 2019: 8 · 2018: 4
- FWCI
- 15.13
- Type
- journal article
- Language
- en
- Update notices
- correction (2020-02-07)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Clinical Oncology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Lirias (KU Leuven) (submittedVersion, other-oa)
- Funders
- Eli Lilly and Company
- Pfizer
- Bayer
- GlaxoSmithKline
- Sanofi
- Gilead Sciences
- Teva Pharmaceutical Industries
- Baxalta
- Taiho Pharmaceutical
- Exelixis
- Jazz Pharmaceuticals
- Leidos
- BeiGene
- Incyte
- Eisai
- National Institutes of Health (UL1TR001863)
- Genentech
- Takeda Oncology
- Pharmacyclics
- National Cancer Institute (U10CA180882, U10CA180820, U10CA180791, UG1CA233290, U10CA180888, U10CA180836, U10CA180790, UG1CA233331, UG1CA233180, U10CA180830, U10CA180795, U10CA180850, U10CA180838, U10CA180867, U10CA180821, UG1CA180830, U10CA180799)
- National Institute of General Medical Sciences (U54GM104942)
- National Center for Advancing Translational Sciences
- Janssen Pharmaceuticals
- Topics
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Health Sciences › Medicine › Oncology › Colorectal Cancer Surgical Treatments
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Keywords
- consensus molecular subtypes, metastatic colorectal cancer, prognostic factors, predictive biomarkers, bevacizumab, cetuximab, first-line chemotherapy, overall survival, progression-free survival, targeted therapy selection
- MeSH terms
- Bevacizumab, Cetuximab, Irinotecan, Oxaliplatin, Aged, Antineoplastic Combined Chemotherapy Protocols, Leucovorin, Female, Fluorouracil, Humans, Male, Middle Aged, Neoplasm Metastasis, Predictive Value of Tests, Prognosis, Colorectal Neoplasms, Gene Expression Regulation, Neoplastic, Treatment Outcome, Disease-Free Survival, Gene Expression Profiling, Kaplan-Meier Estimate
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