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Combination of chemotherapy, targeted drugs appears effective in advanced NSCLC
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The combination of carboplatin, paclitaxel, cetuximab and bevacizumab followed by maintenance cetuximab and bevacizumab demonstrated efficacy and appeared well tolerated in chemotherapy-naive patients with advanced non–small cell lung cancer, according to phase 2 study results.
The SWOG S0536 study included 102 patients (median age, 64 years).
Patients received up to six cycles of carboplatin (area under the curve, 6); 200 mg/m2 paclitaxel; cetuximab [(Erbitux, Eli Lilly) 400 mg/m2 on day 1 followed by weekly 250-mg/m2 doses); and bevacizumab [(Avastin, Genentech), 15 mg/kg every 21 days].
Researchers administered maintenance cetuximab (250 mg/m2 weekly) and bevacizumab (15 mg/kg every 21 days) to patients who achieved an objective response or stable disease. Maintenance continued until disease progression.
Safety — assessed according to the frequency and severity of hemorrhagic toxicities — served as the primary endpoint. Response rate, PFS, OS and toxicity served as secondary endpoints.
Median PFS was 7 months (95% CI, 6-8), and median OS was 15 months (95% CI, 11-21).
Among 95 patients with measurable disease, 52 patients (56%) demonstrated response and 21 patients (22%) achieved stable disease.
The overall disease control rate was 77%.
Grade 4 or higher hemorrhage occurred in 2% of patients (95% CI, 0-7), which met the predefined criteria for safety.
Four treatment-related deaths occurred — two from lung hemorrhage, one from infection and one from an unknown cause.
“The combination regimen showed promising efficacy and was tolerable for patients with advanced lung cancer,” researcher Edward S. Kim, MD, chair of solid tumor oncology and investigational therapeutics at Levine Cancer Institute in Charlotte, N.C., said in a press release. “Dual antibody approaches may better inhibit cell signals that feed the cancer. Our ongoing phase 3 study, SWOG 0819, will address this regimen in a more definitive manner.”
Disclosure: The study was funded in part by Bristol-Myers Squibb and ImClone Systems Inc.
Perspective
Back to TopVamsidhar Velcheti, MD
The phase 2 SWOG S0536 study by Kim and colleagues of carboplatin, paclitaxel and bevacizumab with cetuximab demonstrates efficacy and tolerability of this four-drug regimen as a first-line treatment for advanced non–small cell lung cancer. Even though this study is not practice changing, the overall response rate (56%) and disease control rate (77%) are promising.
The key to incorporating newer biologics into current practice of NSCLC is to have reproducible, validated and clinically feasible biomarkers. The search for biomarkers for both cetuximab and bevacizumab has been particularly frustrating. Even though statistically underpowered, the biomarker analyses in this study appear to be promising — particularly the EGFR H-score and cytokine angiogenesis factor profiling. These results, along with the results from the EGFR H-score analysis in the FLEX trial (Pirker R. Abstract #1557. Presented at: World Conference on Lung Cancer; July 3-7, 2011; Amsterdam) certainly warrant additional investigation of the role of cetuximab in NSCLC and potential biomarkers.
Understandably, there is growing excitement about the ongoing phase 3 SWOG S0819 study of carboplatin/paclitaxel with or without bevacizumab and/or cetuximab in stage IV or recurrent NSCLC. This study should shed light on the validity of these EGFR biomarkers and the role of cetuximab in NSCLC.
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