Effectiveness of Combining Bevacizumab With First-Line Chemotherapy Regimens for Metastatic Colorectal Cancer in Real-World Practice

• Published in: Clinical colorectal cancer 2021-06, Vol.20 (2), p.101-112.e6
• Main Authors: Bang, Yeong Hak, Hong, Yong Sang, Lee, Ji Sung, Lee, Keun-Wook, Han, Hye Sook, Kim, Sun Young, Kim, Ji-Won, Kim, Hee Kyung, Kim, Jin Won, Eun, Choi Ki, Kim, Tae Won, Kim, Jeong Eun
• Format: Article
• Language: English
• Subjects: Anti-VEGF; Colorectal neoplasms; Metastasectomy; Propensity score; Survival analysis
• ISSN: 1533-0028; 1938-0674
• DOI: 10.1016/j.clcc.2020.10.001

Anti–vascular endothelial growth factor (VEGF) agents have shown clinical benefits against metastatic colorectal cancer (mCRC) when combined with cytotoxic chemotherapeutic drugs. Because randomized controlled trials have restrictive enrollment criteria, and because the participants typically do not resemble actual patients, we here investigated the efficacy of bevacizumab as part of a combination therapy for mCRC in a Korean real-world practice setting. We retrospectively evaluated 3748 patients with an initial diagnosis of mCRC or recurrent colorectal cancer with distant metastasis who received first-line chemotherapy in a tertiary cancer center. The primary study endpoint was overall survival. We used multivariate analysis using the Cox regression hazard model and propensity score matching (PSM) methods to adjust for any confounding clinicopathologic factors. Subgroup analysis was also performed for patients who did not receive local treatments for metastatic lesions before receipt of first-line chemotherapy. In an initial crude analysis, patients who received first-line FOLFOX or FOLFIRI showed better survival outcomes if these regimens were combined with bevacizumab (median overall survival, 3.5 vs. 2.3 years; hazard ratio [HR] = 0.66; 95% confidence interval [CI], 0.59-0.73; P < .001). However, Cox regression hazard model adjusted analysis using PSM methods revealed no significant survival differences between these groups (3.0 vs. 2.6 years; HR = 0.92; 95% CI, 0.79-1.07; P = .2612). We performed further survival analysis of 2814 patients with unresectable disease without metastasectomy who received metastatic radiofrequency ablation before chemotherapy. Cox regression and PSM analysis indicated that bevacizumab group showed better survival (HR = 0.82; 95% CI, 0.71-0.94; P = .005; and HR = 0.84; 95% CI, 0.71-0.99; P = .018). The addition of bevacizumab to a first-line chemotherapeutic regimen provides survival benefits in a real-world setting for mCRC patients who cannot undergo curative-intent local treatment for metastatic lesions. •It was unclear whether the marginal benefits of bevacizumab in combination with chemotherapeutics were reproducible in a real-world heterogeneous population.•Bevacizumab produces no survival benefit in metastatic colorectal cancer patients overall when combined with first-line chemotherapeutics in a real-world practice setting•A combination first-line chemotherapy involving bevacizumab is associated, however, with improv