Nadine J McCleary1, Sui Zhang2, Chao Ma2, Fang-Shu Ou3, Tiffany M Bainter3, Alan P Venook4, Donna Niedzwiecki5, Heinz-Josef Lenz6, Federico Innocenti7, Bert H O'Neil8, Blase N Polite9, Howard S Hochster10, James N Atkins11, Richard M Goldberg12, Kimmie Ng13, Robert J Mayer13, Charles D Blanke14, Eileen M O'Reilly15, Charles S Fuchs16, Jeffrey A Meyerhardt13. 1. Dana-Farber Cancer Institute, Boston, MA, United States of America; Harvard Medical School, Boston, MA, United States of America. Electronic address: nj_mccleary@dfci.harvard.edu. 2. Dana-Farber Cancer Institute, Boston, MA, United States of America. 3. Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, MN, United States of America. 4. University of California, San Francisco, CA. 5. Duke University, Durham, NC, United States of America. 6. USC Norris Comprehensive Cancer Center, Los Angeles, CA, United States of America. 7. The University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America. 8. Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN, United States of America. 9. Pritzker School of Medicine, The University of Chicago, Chicago, IL, United States of America. 10. Department of Medical Oncology, Rutgers Cancer Institute of New Jersey, Brunswick, NJ, United States of America. 11. Southeast Cancer Control Consortium, CCOP, Goldsboro, NC, United States of America. 12. West Virginia University Cancer Institute, Morgantown, WV, United States of America. 13. Dana-Farber Cancer Institute, Boston, MA, United States of America; Harvard Medical School, Boston, MA, United States of America. 14. SWOG and Oregon Health & Science University, Portland, OR, United States of America. 15. Memorial Sloan-Kettering Cancer Center, New York, NY, United States of America. 16. Yale Cancer Center and Smillow Cancer Hospital, Yale School of Medicine, New Haven, CT, United States of America.
Abstract
BACKGROUND: Little is known about the interaction of comorbidities and age on survival outcomes in colorectal cancer (mCRC), nor how comorbidities impact treatment tolerance. METHODS: We utilized a cohort of 1345 mCRC patients enrolled in CALGB/SWOG 80405, a multicenter phase III trial of fluorouracil/leucovorin + oxaliplatin (FOLFOX) or irinotecan (FOLFIRI) plus bevacizumab, cetuximab or both. Endpoints were overall survival (OS), progression-free survival (PFS), and grade ≥ 3 toxicities assessed using NCI CTCAE v.3.0. Participants completed a questionnaire, including a modified Charlson Comorbidity Index. Adjusted Cox and logistic regression models tested associations of comorbidities and age on the endpoints. RESULTS: In CALGB/SWOG 80405, 1095 (81%) subjects were < 70 years and >70 250 (19%). Presence of ≥1 comorbidity was not significantly associated with either OS (HR 1.10, 95% CI 0.96-1.25) or PFS (HR 1.03, 95% CI 0.91-1.16). Compared to subjects <70 with no comorbidities, OS was non-significantly inferior for ≥70 with no comorbidities (HR 1.21, 95% CI 0.98-1.49) and significantly inferior for ≥70 with at least one comorbidity (HR 1.51, 95% CI 1.22-1.86). There were no significant associations or interactions between age or comorbidity with PFS. Comorbidities were not associated with treatment-related toxicities. Age ≥ 70 was associated with greater risk of grade ≥ 3 toxicities (OR 2.15, 95% CI 1.50-3.09, p < 0.001). CONCLUSIONS: Among participants in a clinical trial of combination chemotherapy for mCRC, presence of older age with comorbidities was associated with worse OS but not PFS. The association of age with toxicity suggests additional factors of care should be measured in clinical trials.
BACKGROUND: Little is known about the interaction of comorbidities and age on survival outcomes in colorectal cancer (mCRC), nor how comorbidities impact treatment tolerance. METHODS: We utilized a cohort of 1345 mCRC patients enrolled in CALGB/SWOG 80405, a multicenter phase III trial of fluorouracil/leucovorin + oxaliplatin (FOLFOX) or irinotecan (FOLFIRI) plus bevacizumab, cetuximab or both. Endpoints were overall survival (OS), progression-free survival (PFS), and grade ≥ 3 toxicities assessed using NCI CTCAE v.3.0. Participants completed a questionnaire, including a modified Charlson Comorbidity Index. Adjusted Cox and logistic regression models tested associations of comorbidities and age on the endpoints. RESULTS: In CALGB/SWOG 80405, 1095 (81%) subjects were < 70 years and >70 250 (19%). Presence of ≥1 comorbidity was not significantly associated with either OS (HR 1.10, 95% CI 0.96-1.25) or PFS (HR 1.03, 95% CI 0.91-1.16). Compared to subjects <70 with no comorbidities, OS was non-significantly inferior for ≥70 with no comorbidities (HR 1.21, 95% CI 0.98-1.49) and significantly inferior for ≥70 with at least one comorbidity (HR 1.51, 95% CI 1.22-1.86). There were no significant associations or interactions between age or comorbidity with PFS. Comorbidities were not associated with treatment-related toxicities. Age ≥ 70 was associated with greater risk of grade ≥ 3 toxicities (OR 2.15, 95% CI 1.50-3.09, p < 0.001). CONCLUSIONS: Among participants in a clinical trial of combination chemotherapy for mCRC, presence of older age with comorbidities was associated with worse OS but not PFS. The association of age with toxicity suggests additional factors of care should be measured in clinical trials.
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