Abstract
PurposeBevacizumab plus fluoropyrimidine-based chemotherapy is standard treatment for first-line and second-line metastatic colorectal cancer (mCRC). However, to date, there is no current biomarker predictive for the benefit of bevacizumab use for these patients. Preclinical data suggest that the presence of the primary tumor could be involved in less efficient antitumor activity of antiangiogenic agents, but no clinical data currently support this hypothesis.Methods We performed a retrospective analysis of factors associated with overall survival (OS) in a study cohort of 409 mCRC patients. Univariate and multivariate Cox proportional hazard regression models were used to assess the influence of primary tumor resection and bevacizumab use on OS. We evaluated associations linking bevacizumab use and OS among patients who previously underwent or did not undergo primary tumor resection. Results were externally validated in a second independent cohort of 328 mCRC patients.ResultsIn the study cohort, bevacizumab use and resection of the primary tumor were associated with improved OS. However, subgroup analyses indicate that bevacizumab did not influence survival of patients bearing a primary colorectal tumor (hazard ratio (HR) 0.98, 95 % confidence interval (CI) 0.60–1.61, log-rank test P = 0.6). By contrast, the survival benefit of bevacizumab was restricted to patients who previously underwent primary tumor resection (HR 0.71, 95 % CI 0.55–0.92, P = 0.009). Similar results were observed in the validation cohort.ConclusionsAddition of bevacizumab to chemotherapy is associated with improvement of OS only in patients with primary tumor resection. These data support the rationale to validate prospectively the influence of primary tumor resection on bevacizumab antitumor effect in synchronous mCRC.Electronic supplementary materialThe online version of this article (doi:10.1245/s10434-013-3463-y) contains supplementary material, which is available to authorized users.
Highlights
There are no curative options in patients with unresectable metastases from colorectal cancer, but treatment with systemic chemotherapy improves overall survival (OS).[1]
We designed a retrospective clinical study to assess whether the resection of the primary tumor before starting chemotherapy could be associated with patient outcome in metastases from colorectal cancer (mCRC) patients receiving chemotherapy with or without bevacizumab
There was no significant difference between the bevacizumab and chemotherapy-alone groups
Summary
From January 2001 to December 2011, 409 consecutive patients with histologically proven metastatic colorectal adenocarcinoma received first-line chemotherapy treatment at the Georges-Francois Leclerc Cancer Center (Dijon, France) and were prospectively recorded in an institutional clinical database, which made them eligible for this retrospective study. Fortythree patients were included in clinical trials for first- or second-line chemotherapy for metastatic disease involving the use of bevacizumab or cetuximab. This mCRC patient cohort constituted the study cohort. The results obtained for this cohort were validated in an independent validation cohort of 328 consecutive mCRC patients who were treated at Besancon University Hospital from 1997 to 2009. This retrospective study was approved by our Institutional Review Board, and all data were anonymized. If the first infusion was well tolerated, the second was delivered over 60 min; if the 60-min infusion was well tolerated, all subsequent infusions were delivered over 30 min
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