Bevacizumab beyond Progression Prolongs Survival in Metastatic Colorectal Cancer

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In a study highlighted at a press briefing during the 2012 ASCO Annual Meeting, German investigators reported that prolonging treatment with bevacizumab (Avastin) beyond disease progression extends overall survival in patients with metastatic colorectal cancer.1 Patients received bevacizumab plus standard second-line chemotherapy after disease progressed on bevacizumab and first-line therapy.

“This is the first randomized trial to prospectively evaluate bevacizumab beyond first progression. The study confirms that continuing bevacizumab while changing chemotherapy translates into a significant improvement in overall as well as progression-free survival in patients with metastatic colorectal cancer,” said Dirk Arnold, MD, of the University Clinic Eppendorf in Hamburg.

Study Details

The randomized phase III TML 18147 trial enrolled 820 patients with metastatic colorectal cancer who had progressive disease following first-line chemotherapy with an irinotecan- or oxaliplatin-based regimen, plus bevacizumab. Upon disease progression, the patients were randomly assigned to second-line therapy with the regimen they did not receive first, with or without concomitant bevacizumab.

Median overall survival was 11.2 months with continued bevacizumab, compared with 9.8 months with chemotherapy alone, for a 19% reduction in mortality risk (P = .0062). Median progression-free survival was 5.7 vs 4.1 months, respectively, a 32% risk reduction (P < .0001), Dr. Arnold reported.

“There was no sign that the continuation of bevacizumab had an impact on further grade 3 to 5 adverse events,” he further noted. “Rates were already low and similar between the arms.” Adverse events of any grade were noted in 41% of patients receiving bevacizumab/chemotherapy, with 12% grades 3 to 5.

Important Concept

The TML trial tested an important biologic concept for antiangiogenic drugs, showing that duration of treatment does matter. Although the current evidence is in metastatic colorectal cancer, the principle could hold true across lung cancer and breast cancer, Dr. Arnold suggested.

Press briefing moderator Bruce J. Roth, MD, of Washington University in St. Louis, commented that oncologists have been trained to discontinue cytotoxic chemotherapy at the time of progression, “but the issue is more complicated for anti-VEGF [vascular endothelial growth factor] therapies like bevacizumab, and this issue has been raised in other tumor types.” He explained that the mechanism of resistance to anti-VEGF agents may be different, and this might explain the benefit with continued treatment. ■

Disclosure: Dr. Arnold has served in a consulting or advisory role and has received honoraria from Amgen, Merck Serono, and Roche, and has received research funding from Roche. Dr. Roth reported no potential conflicts of interest.


1. Arnold D, Andre T. Bennouna J, et al: Bevacizumab plus chemotherapy continued beyond first progression in patients with metastatic colorectal cancer previously treated with bevacizumab plus chemotherapy: Results of a randomized phase III intergroup study (TML study). 2012 ASCO Annual Meeting. Abstract CRA3503. Presented June 3, 2012.

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