EGFR/VEGF Inhibition Yields Promising Results in NSCLC

Combining both cetuximab and bevacizumab with platinum-based chemotherapy showed strong efficacy in a phase II trial of patients with advanced non–small-cell lung cancer (NSCLC). The study’s results were published in the December issue of the Journal of Thoracic Oncology.

“Progress in chemotherapy-based treatment of NSCLC has been slow,” wrote researchers led by Edward S. Kim, MD, of the Levine Cancer Institute in Charlotte, NC. “Efforts to combine novel targeted agents with chemotherapy have been largely unsuccessful in the majority of trials, partly because of failure to account for the complex biology intrinsic to human lung cancers.” But some previous work that combined bevacizumab with chemotherapy and, separately, cetuximab with chemotherapy, has shown promise. The new trial, Southwest Oncology Group (SWOG) 0536, was a phase II study of a novel regimen involving both of those targeted agents along with chemotherapy as frontline therapy for NSCLC.

A total of 110 patients were enrolled, and 102 of those received up to 6 cycles of carboplatin, paclitaxel, cetuximab, and bevacizumab. Those patients who achieved an objective response or had stable disease then received maintenance cetuximab and bevacizumab until disease progression.

“We were surprised that the efficacy-response, progression-free survival, survival-were the highest ever reported in a lung cancer study from SWOG,” Kim said in an email. The median progression-free survival was 7 months, and the median overall survival was 15 months, and there was a response rate of 56% and an overall disease control rate of 77%; the 1-year survival rate was 57%. Forty-seven patients received maintenance therapy as planned. Notably, neither KRAS nor EGFR mutation status was associated with any difference in clinical outcomes.

Kim added that the regimen was generally well tolerated, “with some additional side effects.” The study’s primary endpoint was grade 4 or higher hemorrhage; this occurred in only 2% of patients (two patients with grade 5 pulmonary hemorrhage), which met the prespecified criteria for safety of the regimen. There were two treatment-related deaths, including one infection and one of unknown cause. The most common grade 3 or greater adverse events were acneiform rash, neutropenia, infection, neuropathy, and fatigue.

Overall, this showed “promising activity for a chemotherapy plus targeted therapy regimen,” Kim said. “It builds on existing drugs, and is currently being validated in a phase III trial.” That trial, which is currently recruiting patients, is the largest current frontline metastatic lung cancer trial, Kim said. It has a planned enrollment of approximately 1,600 patients.