Adding Bevacizumab to Carboplatin/ Paclitaxel Regimen Improves Survival in Patients With Advanced NSCLC

ORLANDO, Florida-Bevacizumab (Avastin) combined with chemotherapy extends survival in advanced, nonsquamous, non-small-cell lung cancer (NSCLC), results of a randomized, multisite trial that tested the combination as first-line therapy show. The findings are expected to change the standard of care, said the investigators who presented their findings at the 41st annual meeting of the American Society of Clinical Oncology (ASCO) (abstract LBA4). New Standard of Care Bevacizumab(Drug information on bevacizumab) with carboplatin(Drug information on carboplatin) and paclitaxel(Drug information on paclitaxel) "is now the ECOG reference standard for the first-line treatment of advanced nonsquamous NSCLC," said Alan Sandler, MD, associate professor of medicine at Vanderbilt-Ingram Cancer Center, who led the trial for the Eastern Cooperative Oncology Group (ECOG). The trial enrolled 878 patients with stage IIIb or IV disease and randomized them to one of two arms. One arm received paclitaxel at 200 mg/m² and carboplatin to an AUC of 6 on day 1 every 3 weeks for six cycles, while the other arm received these two drugs plus bevacizumab at 15 mg/kg on day 1 for six cycles, followed by bevacizumab alone until disease progression or intolerable toxicity. Patients with squamous cell carcinoma were not included in the trial because the risk of serious hemorrhage with bevacizumab is greater in this group. Better Outcomes Patients in the bevacizumab arm had significantly better outcomes. Median survival in this group was 12.5 months, vs 10.2 months for the group that received chemotherapy alone. Theresponse rate in the bevacizumab group was 27.2%, vs 10% for the control group. Median time to progression was 6.4 months vs 4.5 months, respectively. At 1 year, 51.9% of patients in the bevacizumab group were alive, compared with 43.7% in the control group. At 2 years, 22.1% of the bevacizumab patients were alive vs 16.9% of those who received chemotherapy alone. Well-Tolerated Tx Both regimens were well tolerated, Dr. Sandler said, although toxicity was greater on the bevacizumab arm. Grade 4/5 neutropenia was experienced by 24% of the bevacizumab patients vs 16.4% of those on the control arm. Hemorrhage occurred in 4.5% of the patients receiving bevacizumaband in 0.7% of the patients receiving chemotherapy alone. There were 10 treatment-related deaths, 5 of which were caused by hemoptysis and occurred on the bevacizumab arm. Hypertension was significantly greater among those taking bevacizumab- 6% vs 0.7%-but was easily managed with medications, Dr. Sandler said. Bevacizumab is a humanized monoclonal antibody that targets vascular endothelial growth factor (VEGF) and is thought to inhibit the growth of blood vessels feeding the tumor. Lee Ellis, MD, professor of surgical oncology and cancer biology at The University of Texas M.D. Anderson CancerCenter, Houston, discussed the abstract and pointed out that its mechanism of action is still uncertain. "Anti- VEGF therapy inhibits activity of both endothelial cells and some tumor cells," he said in his discussion of the results."We do think that anti-VEGFCenter, Houston, discussed the abstract and pointed out that its mechanism of action is still uncertain. "Anti- VEGF therapy inhibits activity of both endothelial cells and some tumor cells," he said in his discussion of the results. "We do think that anti-VEGFtherapy is antiangiogenic, though this is very difficult to prove in clinical trials, and I think we will have a hard time proving this in the future. But efficacy is what counts." Dr. Ellis added that it would be very useful to develop predictive markersfor bevacizumab, not only for outcome but also for adverse events. "We need to be cognizant of the adverse effects," he emphasized, "including hypertension, bowel perforation, and hemorrhage. Although infrequent, they are important adverse events."