By Joanna Lyford, Senior medwireNews Reporter
A four-drug combination of cetuximab, bevacizumab, carboplatin, and paclitaxel is effective and has acceptable safety as a first-line treatment for advanced non-small-cell lung cancer (NSCLC), US researchers report.
The regimen is now being studied in a phase III trial, raising hopes of a new therapeutic approach for the disease.
The SWOG S0536 trial, led by Edward Kim (Levine Cancer Institute, Charlotte, North Carolina, USA), included 102 treatment-naïve patients with stage IIIB/IV nonsquamous NSCLC.
They were treated with up to six cycles of carboplatin (area under the curve of 6), paclitaxel (200 mg/m2), cetuximab (400 mg/m2 day 1 then 250 mg/m2 weekly), and bevacizumab (15 mg/kg) every 21 days.
Forty-seven patients had an objective response or stable disease and also received maintenance therapy with cetuximab (250 mg/m2 weekly) and bevacizumab (15 mg/kg every 21 days) until disease progression.
The trial’s primary endpoint was grade 4 or higher hemorrhage. This occurred in two patients (2%), which was within the predefined safety margin. Both hemorrhages were fatal pulmonary hemorrhages; there were two further treatment-related deaths, one due to infection and one of unknown cause.
The most common grade 3 or higher adverse events were acneiform rash, neutropenia, infection, neuropathy, and fatigue.
In terms of efficacy, the overall response rate was 56% and the disease control rate was 77%, Kim et al report in the Journal of Thoracic Oncology. The estimated median progression-free survival was 7 months and median overall survival was 15 months.
A secondary purpose of the trial was to investigate prognostic biomarkers. Molecular analysis of tumors from 66 patients found that outcomes did not differ significantly by epidermal growth factor receptor (EGFR) fluorescent in-situ hybridization status. However, progression-free survival was better in patients with mutant KRAS than in those with wild-type KRAS, although overall survival did not differ between these groups.
“On the basis of the S0536 observations described here, additional biomarkers such as EGFR protein H score and [cytokine-angiogenesis factor] profiling, which we present as preliminary results here, are being evaluated in the phase III S0819 study as well,” Kim et al note.
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