ATLANTA — Bevacizumab (Avastin) in combination with erlotinib (Tarceva) was associated with promising preliminary results in the treatment of refractory non-small cell lung cancer in data presented at the annual meeting of the American Society of Clinical Oncology.
The 17.9% response rate with the bevacizumab-erlotinib combination was better than the 12.5% rate seen in patients treated with bevacizumab and chemotherapy and the 12.2% rate seen in those treated chemotherapy alone.
Dr. Louis Fehrenbacher reported that 31 of 39 patients treated with bevacizumab and erlotinib were alive at 6 months. With bevacizumab and chemotherapy, 29 of 40 were still alive at 6 months.
The two bevacizumab arms also had similar progression-free survival: 4.8 months when the angiogenesis inhibitor was combined with chemotherapy and 4.4 months when it was used with erlotinib.
A control arm of 41 patients treated only with chemotherapy (either pemetrexed or docetaxel) had the worst outcomes. Only 26 of those patients were alive at 6 months. Median progression-free survival was just 3 months.
Dr. Fehrenbacher of Kaiser Permanente Vallejo Medical Center in California and his coinvestigators reported that about one-third of both bevacizumab arms and about one-fifth of the chemotherapy-only patients were progression free at 6 months. The investigators calculated adjusted hazard ratios of 0.66 for bevacizumab with chemotherapy and 0.72 for bevacizumab with erlotinib, compared with the chemotherapy arm.
“Overall I think this is a very encouraging finding that the [bevacizumab-erlotinib] combination may actually work in a refractory situation,” Dr. Tony Mok said in a discussion of the poster.
Dr. Mok, of the Chinese University of Hong Kong, said the results challenge the belief that combining agents is not worthwhile for second-line treatment of non-small cell lung cancer. It also raises questions, he said, about how bevacizumab works and how bevacizumab and chemotherapy work together. Instead of treating chemotherapies as interchangeable with bevacizumab, he said, clinicians need to find the best combination.
One-year data are not yet available for the trial, which enrolled patients with locally advanced or metastatic (stages IIb-IV), nonsquamous non-small cell lung cancer. The study excluded patients with brain metastases.
Bevacizumab, a monoclonal antibody marketed by Genentech in the United States and by Roche worldwide, helps to cut off blood supply to tumors by inhibiting vascular endothelial growth factor. It is approved for use in combination with chemotherapy for the treatment of metastatic colorectal cancer.
Erlotinib, produced by OSI Pharmaceuticals, targets the human epidermal growth factor receptor pathway, which also plays a role in promoting tumor growth. It is approved for use as monotherapy in patients with locally advanced or metastatic non-small cell lung cancer that has progressed on chemotherapy.
Beyond the juggling of similar benefits in the two bevacizumab arms, the much-anticipated phase II trial showed less toxicity overall when patients were treated with two targeted therapies instead of chemotherapy alone or in combination.
Only four patients (10%) in the bevacizumab-erlotinib arm discontinued treatment because of adverse events, compared with 10 patients in each of the chemotherapy arms. The trial reported serious events in 13 bevacizumab-erlotinib patients (33%), 16 bevacizumab-chemotherapy patients (40%), and 22 chemotherapy-only patients (54%). One chemotherapy-only patient died of cardiopulmonary arrest. No chemotherapy-only patients had pulmonary hemorrhage, a growing concern for patients treated with angiogenic inhibitors.
Two fatal pulmonary hemorrhages and a fatal gastrointestinal bleed occurred in patients treated with bevacizumab and chemotherapy. One patient in the bevacizumab-erlotinib arm died of a pulmonary hemorrhage.
Dr. Roy S. Herbst, senior author of the trial, noted that two much larger studies are already exploring the bevacizumab-erlotinib combination as first- and second-line therapies in non-small cell lung cancer. Dr. Herbst, chief of thoracic medical oncology at M.D. Anderson Cancer Center in Houston, said about 1,800 patients are to be enrolled in these studies, which will test the targeted agents alone and in combination against chemotherapy.
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