Phase II study of pemetrexed, carboplatin, and thoracic radiation with or without cetuximab in patients with locally advanced...

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Author(s): R. Govindan, J. Bogart, X. Wang, L. Hodgson, R. Kratzke, E. E. Vokes, for the Cancer and Leukemia Group B; Washington University School of Medicine, St. Louis, MO; State University of New York, New York, NY; Duke University, Durham, NC; University of Minnesota, Minneapolis, MN; University of Chicago, Chicago, IL
 
Abstract:
Background: Cisplatin, etoposide and concurrent thoracic radiation has remained the standard treatment for locally advanced unresectable non small cell lung cancer (NSCLC) over the past two decades. The Cancer and Leukemia Group B (CALGB) conducted a phase II study using a novel chemotherapy regimen administered in systemically active doses with thoracic radiation (CALGB 30407). We previously reported the preliminary safety results (ASCO 2008, abstract 7518).
 
Methods: Eligible patients with previously untreated stage III NSCLC received thoracic radiation (70 Gy) along with carboplatin (AUC 5) and pemetrexed 500 mg/m2 on day 1 administered intravenously every 21 days for 4 cycles (arm A) or the same chemotherapy regimen with weekly cetuximab for 6 weeks concurrent with radiation (arm B). All patients received four additional cycles of pemetrexed (500 mg/m2 every 21 days) as consolidation therapy. The primary endpoint was the percentage of patients who lived longer than 18 months after starting initial treatment. We planned to study the regimen (s) further if the 18 month survival rates equaled or exceeded 55%.
 
Results: Characteristics of the 99 eligible pts (48 in arm A and 51 arm B) enrolled from 09/05 to 1/08: male 62%, 22% were 70 yrs or older. The most common histological type was adenocarcinoma (46% in Arm A and 41% in Arm B). Updated toxicity data (grade 3 or greater, %) by arms (arm A/arm B) for 106 pts: neutropenia 40/47; febrile neutropenia 8/6, thrombocytopenia 36/34, nausea/vomiting 8/10, esophagitis 32/24, skin rash 2/21 and fatigue 22/17. The median follow up time is 17 months. Preliminary efficacy data by arms (arm A/arm B) for 99 pts: complete or partial response 73% (95% CI 59-83)/71% (95% CI 57-81%), median failure free survival (months) 12.9 (95% CI 8.6-18.0)/10.3 (95% CI 8.7-18.9); 18 month survival 57% (95% CI 41-79)/47% (95% CI 33-67) and median survival (months) 22.3/18.7.
 
Conclusions: The combination of pemetrexed, carboplatin and thoracic radiation has met the protocol-specified criteria for further study. Although it does not appear that the addition of cetuximab confers additional benefit in this setting, further follow-up is necessary.