Treatment with bevacizumab beyond progression: A new standard in mCRC?
The addition of bevacizumab (BEV) to 5-FU-based chemotherapy has been a standard 1st-line treatment option for patients with metastatic colorectal cancer (mCRC) for many years, although the use of this agent beyond progression is an area of ongoing debate. However, emerging data suggest that this question may soon be answered
In proffered papers session at ESMO 2012 in Vienna, Dr Gianluca Masi from the University Hospital of Pisa, Italy, presented data from a randomized Phase 3 trial, conducted by the Gruppo Oncologico Nord Ovest (GONO), which evaluated the continuation of bevacizumab beyond progression in patients with mCRC who had received bevacizumab as part of their 1st-line therapy. In this trial, 184 patients who had progressed following 1st-line chemotherapy (FOLFOX, FOLFIRI or FOLFOXIRI) + bevacizumab were randomized to receive 2nd- line treatment with chemotherapy alone (either FOLFOX or mFOLFIRI) or in combination with bevacizumab 5 mg/kg every 2 weeks.
Despite accrual to this trial being stopped early, results showed that the addition of BEV was associated with a significant progression- free survival (PFS) benefit compared with chemotherapy alone (median PFS: 6.77 months versus 4.97 months; HR 0.65; 95% CI: 0.48–0.89, p=0.0062), and that this benefit was maintained across various patient subgroups. The safety profile of bevacizumab + chemotherapy was consistent with previously reported data. However, Dr Masi advised that overall survival (OS) data are still immature at this time, with only 46 and 52 events observed in the bevacizumab + chemotherapy and chemotherapy alone arms, respectively.
The decision to stop accrual to this trial was based on results from the similarly designed Treatment- across Multiple Lines (TML) trial reported in June 2012, which showed that bevacizumab continued with 2nd-line chemotherapy was associated with a significant improvement in OS in patients with mCRC.
“This is the second randomized trial investigating the impact of bevacizumab continuation beyond first progression”, concluded Dr Masi. “The continuation of bevacizumab in combination with second-line chemotherapy represents a new treatment option”, he added.