Effect of bevacizumab in older patients with metastatic colorectal cancer: pooled analysis of four randomized studies
Bevacizumab is frequently combined with 5-fluorouracil-based chemotherapy for patients with metastatic colorectal cancer (mCRC). The relative benefit of bevacizumab in older patients has not been widely studied and is of interest.
Patients and methods
This retrospective analysis used data from three first-line randomized controlled studies and one second-line randomized controlled study of bevacizumab plus chemotherapy in medically fit (Eastern Cooperative Oncology Group performance status 0 or 1) patients with mCRC. Overall survival (OS) and on-treatment progression-free survival (PFS) were assessed in patients aged <65, ≥65, and ≥70 years. Results were compared using unstratified hazard ratios (HRs). Grade 3–5 adverse events were also assessed.
Bevacizumab statistically significantly improved PFS [HR 0.58; 95% confidence interval (CI) 0.49–0.68] and OS (HR 0.85; 95% CI 0.74–0.97) in patients aged ≥65 years; patients aged ≥70 years had similar improvements. Benefits were consistent across the studies, irrespective of setting, bevacizumab dose, or chemotherapy regimen. Increases in thromboembolic events were observed in patients aged ≥65 and ≥70 years in the bevacizumab group compared with the control group, mainly as a result of increases in arterial thromboembolic events. No other substantial age-related increases in grade 3–5 adverse events were observed.
In medically fit older patients, bevacizumab provides similar PFS and OS benefits as in younger patients.
- Abbott RD, Curb JD, Rodriguez BL, Masaki KH, Popper JS, Ross GW, Petrovitch H (2003) Age-related changes in risk factor effects on the incidence of thromboembolic and hemorrhagic stroke. J Clin Epidemiol 56:479–486 CrossRef
- Edwards BK, Howe HL, Ries LA, Thun MJ, Rosenberg HM, Yancik R, Wingo PA, Jemal A, Feigal EG (2002) Annual report to the nation on the status of cancer, 1973–1999, featuring implications of age and aging on U.S. cancer burden. Cancer 94:2766–2792 CrossRef
- Folprecht G, Cunningham D, Ross P, Glimelius B, Di Costanzo F, Wils J, Scheithauer W, Rougier P, Aranda E, Hecker H, Köhne CH (2004) Efficacy of 5-fluorouracil-based chemotherapy in elderly patients with metastatic colorectal cancer: a pooled analysis of clinical trials. Ann Oncol 15:1330–1338 CrossRef
- Folprecht G, Seymour MT, Saltz L, Douillard JY, Hecker H, Stephens RJ, Maughan TS, Van Cutsem E, Rougier P, Mitry E, Schubert U, Köhne CH (2008) Irinotecan/fluorouracil combination in first-line therapy of older and younger patients with metastatic colorectal cancer: combined analysis of 2,691 patients in randomized controlled trials. J Clin Oncol 26:1443–1451 CrossRef
- Giantonio BJ, Catalano PJ, Meropol NJ, O’Dwyer PJ, Mitchell EP, Alberts SR, Schwartz MA, Benson AB 3rd, Eastern Cooperative Oncology Group Study E3200 (2007) Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol 25:1539–1544 CrossRef
- Goldberg RJ, Gore JM, Gurwitz JH, Alpert JS, Brady P, Strohsnitter W, Chen ZY, Dalen JE (1989) The impact of age on the incidence and prognosis of initial acute myocardial infarction: the Worcester Heart Attack Study. Am Heart J 117:543–549 CrossRef
- Goldberg RM, Tabah-Fisch I, Bleiberg H, de Gramont A, Tournigand C, Andre T, Rothenberg ML, Green E, Sargent DJ (2006) Pooled analysis of safety and efficacy of oxaliplatin plus fluorouracil/leucovorin administered bimonthly in elderly patients with colorectal cancer. J Clin Oncol 24:4085–4091 CrossRef
- Hurwitz H, Saini S (2006) Bevacizumab in the treatment of metastatic colorectal cancer: safety profile and management of adverse events. Semin Oncol 33(5 Suppl 10):S26–S34 CrossRef
- Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, Ferrara N, Fyfe G, Rogers B, Ross R, Kabbinavar F (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350:2335–2342 CrossRef
- Kabbinavar FF, Hambleton J, Mass RD, Hurwitz HI, Bergsland E, Sarkar S (2005) Combined analysis of efficacy: the addition of bevacizumab to fluorouracil/leucovorin improves survival for patients with metastatic colorectal cancer. J Clin Oncol 23:3706–3712 CrossRef
- Kabbinavar F, Hurwitz H, Yi J, Rosen O (2009) Addition of bevacizumab to fluorouracil-based first-line treatment of metastatic colorectal cancer: pooled analysis of cohorts of older patients from two randomized trials. J Clin Oncol 27:199–205 CrossRef
- Kozloff MF, Sugrue M, Purdie DM, Flynn PJ, Kabbinavar F, Sargent D, Purdie DM, Dong W, Grothey A (2008) Safety and effectiveness of bevacizumab (BV) and chemotherapy (CT) in elderly patients (pts) with metastatic colorectal cancer (mCRC): results from the BRiTE observational cohort study. J Clin Oncol 26(15S):Abstract 4026
- Saltz LB, Clarke S, Díaz-Rubio E, Scheithauer W, Figer A, Wong R, Koski S, Lichinitser M, Yang TS, Rivera F, Couture F, Sirzén F, Cassidy J (2008) Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol 26:2013–2019 CrossRef
- Scappaticci FA, Skillings JR, Holden SN, Gerber HP, Miller K, Kabbinavar F, Bergsland E, Ngai J, Holmgren E, Wang J, Hurwitz H (2007) Arterial thromboembolic events in patients with metastatic carcinoma treated with chemotherapy and bevacizumab. J Natl Cancer Inst 99:1232–1239 CrossRef
- Silverstein MD, Heit JA, Mohr DN, Petterson TM, O’Fallon WM, Melton LJ 3rd (1998) Trends in the incidence of deep vein thrombosis and pulmonary embolism: a 25-year population-based study. Arch Intern Med 158:585–593 CrossRef
- Effect of bevacizumab in older patients with metastatic colorectal cancer: pooled analysis of four randomized studies
- Open Access
- Available under Open Access This content is freely available online to anyone, anywhere at any time.
Journal of Cancer Research and Clinical Oncology
Volume 136, Issue 5 , pp 737-743
- Cover Date
- Print ISSN
- Online ISSN
- Additional Links
- Metastatic colorectal cancer
- Older patients
- Pooled analysis
- Industry Sectors
- Author Affiliations
- 1. Cancer Research UK, Glasgow, UK
- 2. Memorial Sloan-Kettering Cancer Center, New York, NY, USA
- 3. University of Pennsylvania, Philadelphia, PA, USA
- 4. UCLA School of Medicine, Los Angeles, CA, USA
- 5. Duke University Medical Center, Durham, NC, USA
- 6. F. Hoffmann-La Roche, Basel, Switzerland