Impact of Primary Tumor Site on Bevacizumab Efficacy in Metastatic Colorectal Cancer

Hui-Li Wong; Belinda Lee; Kathryn Field; Anna Lomax; Mark Tacey; Jeremy Shapiro; Joe McKendrick; Allan Zimet; Desmond Yip; Louise Nott; Ross Jennens; Gary Richardson; Jeanne Tie; Suzanne Kosmider; Phillip Parente; Lionel Lim; Prasad Cooray; Ben Tran; Jayesh Desai; Rachel Wong; Peter Gibbs

doi:10.1016/j.clcc.2016.02.007

Impact of Primary Tumor Site on Bevacizumab Efficacy in Metastatic Colorectal Cancer

Clin Colorectal Cancer. 2016 Jun;15(2):e9-e15. doi: 10.1016/j.clcc.2016.02.007. Epub 2016 Feb 13.

Authors

Hui-Li Wong¹, Belinda Lee², Kathryn Field³, Anna Lomax⁴, Mark Tacey⁵, Jeremy Shapiro⁶, Joe McKendrick⁴, Allan Zimet⁷, Desmond Yip⁸, Louise Nott⁹, Ross Jennens⁷, Gary Richardson¹⁰, Jeanne Tie¹¹, Suzanne Kosmider¹², Phillip Parente⁴, Lionel Lim¹³, Prasad Cooray⁴, Ben Tran¹, Jayesh Desai³, Rachel Wong¹⁴, Peter Gibbs¹⁵

Affiliations

¹ Systems Biology and Personalised Medicine Division, Walter & Eliza Hall Institute of Medical Research (WEHI), Parkville, Melbourne, Australia; Department of Medical Oncology, The Royal Melbourne Hospital, Parkville, Melbourne, Victoria, Australia.
² Systems Biology and Personalised Medicine Division, Walter & Eliza Hall Institute of Medical Research (WEHI), Parkville, Melbourne, Australia; Department of Medical Oncology, The Royal Melbourne Hospital, Parkville, Melbourne, Victoria, Australia; Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia. Electronic address: Belinda.lee@mh.org.au.
³ Department of Medical Oncology, The Royal Melbourne Hospital, Parkville, Melbourne, Victoria, Australia.
⁴ Eastern Health, Department of Medical Oncology, Melbourne, Victoria, Australia.
⁵ Department of Medical Oncology, The Royal Melbourne Hospital, Parkville, Melbourne, Victoria, Australia; Department of Health Education and Research, Melbourne EpiCentre, The Royal Melbourne Hospital, Parkville, Melbourne, Victoria, Australia.
⁶ Cabrini Health, Department of Oncology, Malvern, Melbourne, Victoria, Australia; Department of Medicine, Nursing & Health Sciences, Monash University, Parkville, Melbourne, Victoria, Australia.
⁷ Department of Oncology, Epworth Hospital, Richmond, Victoria, Australia.
⁸ Department of Medical Oncology, Canberra and Calvary Hospitals, Garran, Australian Capital Territory, Australia.
⁹ Department of Medical Oncology, Royal Hobart Hospital, Hobart, Tasmania, Australia.
¹⁰ Cabrini Health, Department of Oncology, Malvern, Melbourne, Victoria, Australia.
¹¹ Systems Biology and Personalised Medicine Division, Walter & Eliza Hall Institute of Medical Research (WEHI), Parkville, Melbourne, Australia; Department of Medical Oncology, The Royal Melbourne Hospital, Parkville, Melbourne, Victoria, Australia; Western Health, Department of Medical Oncology, Footscray, Melbourne, Victoria, Australia.
¹² Western Health, Department of Medical Oncology, Footscray, Melbourne, Victoria, Australia.
¹³ Eastern Health, Department of Medical Oncology, Melbourne, Victoria, Australia; Department of Oncology, Ringwood Private Hospital, Ringwood East, Victoria, Australia.
¹⁴ Systems Biology and Personalised Medicine Division, Walter & Eliza Hall Institute of Medical Research (WEHI), Parkville, Melbourne, Australia; Eastern Health, Department of Medical Oncology, Melbourne, Victoria, Australia; Department of Medicine, Nursing & Health Sciences, Monash University, Parkville, Melbourne, Victoria, Australia.
¹⁵ Systems Biology and Personalised Medicine Division, Walter & Eliza Hall Institute of Medical Research (WEHI), Parkville, Melbourne, Australia; Department of Medical Oncology, The Royal Melbourne Hospital, Parkville, Melbourne, Victoria, Australia; Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia; Western Health, Department of Medical Oncology, Footscray, Melbourne, Victoria, Australia.

PMID: 26968236
DOI: 10.1016/j.clcc.2016.02.007

Abstract

Background: With an ever-increasing focus on personalized medicine, all factors known to affect treatment response need to be considered when defining optimal therapy for individual patients. While the prognostic impact of primary tumor site on colorectal cancer (CRC) outcomes is established, emerging data suggest potential differences in response to biologic therapies. We studied the impact of tumor site on bevacizumab efficacy in patients with metastatic CRC.

Patients and methods: We analyzed data of patients in an Australian prospective multicenter metastatic CRC (mCRC) registry who received first-line chemotherapy. Tumor site was defined as right colon, cecum to transverse; left colon, splenic flexure to rectosigmoid; and rectum. Kaplan-Meier and Cox models were used for survival analyses.

Results: Of 926 patients, 297 had right colon, 354 left colon, and 275 rectum primary disease. Median age was 68.6, 65.9, and 63.3 years, respectively (P = .001). Right colon disease was significantly associated with intraperitoneal spread (P < .0001), while left colon and rectum disease preferentially metastasized to the liver and lungs, respectively (P < .0001 in both settings). A total of 636 patients (68.7%) received bevacizumab. Progression-free survival was superior for bevacizumab-treated patients in all groups but appeared greatest in right colon disease (hazard ratio, 0.46; 95% confidence interval, 0.36-0.60; P ≤ .001). Overall survival was longest in patients with disease of the rectum, followed by left colon and right colon (median, 26.2, 23.6, and 18.2 months, respectively; P = .0004).

Conclusion: Tumor site appears to be prognostic in mCRC, with rectum and right colon disease associated with the best and worst outcomes, respectively. Patients who received bevacizumab in addition to chemotherapy had superior outcomes, with the effect appearing greatest in patients with right colon disease.

Keywords: Anti-VEGF therapy; Bowel cancer; Distal colorectal cancer; Personalized medicine; Proximal colorectal cancer.

Publication types

Multicenter Study
Observational Study

MeSH terms

Adult
Aged
Aged, 80 and over
Antineoplastic Agents / therapeutic use*
Bevacizumab / therapeutic use*
Colorectal Neoplasms / drug therapy*
Colorectal Neoplasms / mortality
Colorectal Neoplasms / pathology*
Disease-Free Survival
Female
Humans
Kaplan-Meier Estimate
Male
Middle Aged
Neoplasm Metastasis
Prognosis
Proportional Hazards Models
Prospective Studies
Registries
Treatment Outcome

Substances

Antineoplastic Agents
Bevacizumab