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Observational Study
. 2020 Nov 1;6(11):1713-1721.
doi: 10.1001/jamaoncol.2020.3938.

Association of Coffee Intake With Survival in Patients With Advanced or Metastatic Colorectal Cancer

Christopher Mackintosh  1 , Chen Yuan  2 , Fang-Shu Ou  3 , Sui Zhang  2 , Donna Niedzwiecki  4 , I-Wen Chang  5 , Bert H O'Neil  6 , Brian C Mullen  3 , Heinz-Josef Lenz  7 , Charles D Blanke  8 , Alan P Venook  9 , Robert J Mayer  2 , Charles S Fuchs  10 , Federico Innocenti  11 , Andrew B Nixon  12 , Richard M Goldberg  13 , Eileen M O'Reilly  14 , Jeffrey A Meyerhardt  2 , Kimmie Ng  2
Affiliations
Observational Study

Association of Coffee Intake With Survival in Patients With Advanced or Metastatic Colorectal Cancer

Christopher Mackintosh et al. JAMA Oncol. .

Abstract

Importance: Several compounds found in coffee possess antioxidant, anti-inflammatory, and insulin-sensitizing effects, which may contribute to anticancer activity. Epidemiological studies have identified associations between increased coffee consumption and decreased recurrence and mortality of colorectal cancer. The association between coffee consumption and survival in patients with advanced or metastatic colorectal cancer is unknown.

Objective: To evaluate the association of coffee consumption with disease progression and death in patients with advanced or metastatic colorectal cancer.

Design, setting, and participants: This prospective observational cohort study included 1171 patients with previously untreated locally advanced or metastatic colorectal cancer who were enrolled in Cancer and Leukemia Group B (Alliance)/SWOG 80405, a completed phase 3 clinical trial comparing the addition of cetuximab and/or bevacizumab to standard chemotherapy. Patients reported dietary intake using a semiquantitative food frequency questionnaire at the time of enrollment. Data were collected from October 27, 2005, to January 18, 2018, and analyzed from May 1 to August 31, 2018.

Exposures: Consumption of total, decaffeinated, and caffeinated coffee measured in cups per day.

Main outcomes and measures: Overall survival (OS) and progression-free survival (PFS).

Results: Among the 1171 patients included in the analysis (694 men [59%]; median age, 59 [interquartile range, 51-67] years). The median follow-up time among living patients was 5.4 years (10th percentile, 1.3 years; IQR, 3.2-6.3 years). A total of 1092 patients (93%) had died or had disease progression. Increased consumption of coffee was associated with decreased risk of cancer progression (hazard ratio [HR] for 1-cup/d increment, 0.95; 95% CI, 0.91-1.00; P = .04 for trend) and death (HR for 1-cup/d increment, 0.93; 95% CI, 0.89-0.98; P = .004 for trend). Participants who consumed 2 to 3 cups of coffee per day had a multivariable HR for OS of 0.82 (95% CI, 0.67-1.00) and for PFS of 0.82 (95% CI, 0.68-0.99), compared with those who did not drink coffee. Participants who consumed at least 4 cups of coffee per day had a multivariable HR for OS of 0.64 (95% CI, 0.46-0.87) and for PFS of 0.78 (95% CI, 0.59-1.05). Significant associations were noted for both caffeinated and decaffeinated coffee.

Conclusions and relevance: Coffee consumption may be associated with reduced risk of disease progression and death in patients with advanced or metastatic colorectal cancer. Further research is warranted to elucidate underlying biological mechanisms.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Ou reported receiving grants from the National Cancer Institute (NCI) during the conduct of the study and outside the submitted work. Dr O’Neil reported other from Eli Lilly and Company outside the submitted work. Dr Blanke reported receiving grants from the NCI during the conduct of the study. Dr Venook reported receiving grants from the National Institutes of Health (NIH) during the conduct of the study and grants from Genentech/Roche outside the submitted work. Dr Fuchs reported receiving personal fees from Agios Pharmaceuticals, Inc, Amylin Pharmaceuticals, Bain Capital, CytomX Therapeutics, Inc, Daiichi-Sankyo Company, Limited, Eli Lilly and Company, Entrinsic Health, EvolveImmune Therapeutics, Inc, Genentech, Inc, Merck & Co, Taiho Pharmaceutical Co, Ltd, and Unum Therapeutics, Inc, outside the submitted work; serving as a director for CytomX Therapeutics, Inc; owning unexercised stock options for CytomX Therapeutics, Inc, and Entrinsic Health; co-founding and having equity in EvolveImmune Therapeutics, Inc; and providing expert testimony for Amylin Pharmaceuticals and Eli Lilly and Company. Dr Nixon reported receiving personal fees from Pfizer, Inc, Chendu Kanghong Pharmaceutical Group Co, Ltd, Eli Lilly and Company, and Promega Corporation and grants from Acceleron Pharma, Inc, Amgen, Inc, AstraZeneca/MedImmune, Eureka Therapeutics, Genentech, Inc, Leadiant Biosciences, Inc, MedPacto, Inc, Seattle Genetics, Inc, and Tracon Pharmaceuticals, Inc, outside the submitted work; and having patents to Methods of Developing a Prognosis For Pancreatic Cancer and Predicting Responsiveness to Cancer Therapeutics issued and patents to Methods of Predicting Responsiveness of a Cancer to a VEGF Targeting Agent and Methods of Prognosing and Treating Cancer pending. Dr Goldberg reported receiving personal fees from Genentech, Inc, Taiho Pharmaceutical Co, Ltd, Novartis International AG, and Merck & Co outside the submitted work. Dr O’Reilly reported receiving grants from Acta Biologica, MabVax Therapeutics Holdings, Inc, Celgene Corporation, AstraZeneca, and Silenseed and personal fees from Ipsen Group, Rafael Therapeutics, CytomX Therapeutics, Inc, Merck & Co, Polaris Pharmaceuticals, and Swedish Orphan Biovitrum AB outside the submitted work. Dr Meyerhardt reported receiving personal fees from Taiho Pharmaceutical Co, Ltd, COTA Healthcare, and Ignyta, Inc, outside the submitted work. Dr Ng reported receiving grants from the NCI, the Department of Defense, and Cancer Research UK during the conduct of the study and grants and nonfinancial support from Pharmavite, LLC, grants from Revolution Medicines, Inc, Evergrande Group, Genentech, Inc, Gilead Sciences, Inc, Celgene Corporation, TrovaGene, Inc, and Tarrex Biopharma, Ltd, and personal fees from Bayer, Seattle Genetics, Inc, and Array BioPharma, Inc, outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Derivation of the Study Population
Figure 2.
Figure 2.. Overall (OS) and Progression-Free (PFS) Survival by Frequency of Total Coffee Consumption
Patients who consumed 1 cup/d or less were grouped into a single category for ease of graphic viewing. A, Median OS for patients who never consumed coffee was 31 (interquartile range [IQR], 16-46) months; 1 or fewer cups/d, 30 (IQR, 17-49) months; 2 to 3 cups/d, 32 (IQR, 19-50) months; and 4 or more cups/d, 39 (IQR, 19-67) months. B, Median PFS for patients who never consumed coffee was 12 (IQR, 8-18) months; 1 or fewer cups/d, 12 (IQR, 8-19) months; 2 to 3 cups/d, 13 (IQR, 9-21) months; and 4 or more cups/d, 14 (IQR, 9-21) months. The log-rank P value for trend was calculated by using frequency of consumption as a continuous variable.
Figure 3.
Figure 3.. Multivariable-Adjusted Hazard Ratios (HRs) and 95% CIs for Overall and Progression-Free Survival
Data are calculated per 1-cup/d increment in total coffee consumption, across strata of covariates and adjusted for age (continuous), total energy intake (continuous), sex (female or male), Eastern Cooperative Oncology Group (ECOG) performance status (0 or 1-2), prior adjuvant chemotherapy (yes or no), chemotherapy backbone (leucovorin, fluorouracil, and oxaliplatin [mFOLFOX6] or leucovorin, fluorouracil, and irinotecan [FOLFIRI]), assigned treatment arm (bevacizumab, cetuximab, or bevacizumab plus cetuximab), body mass index (continuous), and physical activity (continuous), excluding the stratification variable. MET indicates metabolic equivalent; P (I), P value for interaction.
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Comment in

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