Konference: 2008 33st Congress ESMO - účast ČR
Kategorie: Zhoubné nádory plic a průdušek
Téma: Oncology highlights 2008
Číslo abstraktu: 730
Autoři: W. E. Eberhardt; J. von Pawel; I. Vynnychenko; prof. MUDr. Petr Zatloukal (1955-2012), CSc.; F. De Marinis; K. O’Byrne; U. Gatzemeier; L. G. Paz-Ares; MD Michael Emig; Prof., Mag., Dr. Robert Pirker
Objectives: To demonstrate survival improvement for the
EGFR-targeted monoclonal antibody cetuximab (Erbitux®) in
combination with CT compared to CT alone in 1stline NSCLC.
Methods: In this phase III multicenter, multinational study, patients with EGFR expressing advanced NSCLC were randomized 1:1 to CT (cisplatin 80 mg/m2 d1 and vinorelbine 25 mg/m2 d1, d8 q3w) + cetuximab (400 mg/m2 initial dose, then 250 mg/m2/wk) or CT alone. The primary endpoint was overall survival (OS) and secondary endpoints included tumor response, progression-free survival (PFS), disease control,and safety.
Results: A total of 1125 patients were randomized: 557 to CT + cetuximab and 568 to CT alone. Median age: 59 (range 18–83) years; male: 70%; stage IV: 94%; adenocarcinoma: 47%; squamous cell carcinoma: 34%; ECOG performance status 0/1: 83%. Survival analysis was performed as preplanned after 868 events. OS was significantly improved in the CT + cetuximab arm vs CT (median 11.3 vs 10.1 months; HR [95% CI]: 0.871 [0.762–0.996]; p=0.0441). Results from prespecified subgroup analyses demonstrate that the addition of cetuximab provides a greater benefit in Caucasians (n=946; HR [95% CI]: 0.803 [0.694–0.928]; p=0.003) across all histologies. The response rate was significantly improved in the CT + cetuximab arm vs CT (36.3 vs 29.2%; 95% CI: 32.3–40.4 and 25.5–33.2; p=0.012). PFS was comparable in both arms whereas time to treatment failure was significantly improved with CT + cetuximab (4.2 vs 3.6 months; HR [95% CI]: 0.859 [0.760–0.970]; p=0.015). Treatment was generally well tolerated. The most common grade 3/4 adverse events (CT + cetuximab vs CT) were: neutropenia 52.7% vs 51.4%; febrile neutropenia 21.7% vs 15.5%; anemia 13.9% vs 16.7%; acne-like rash 10.4% vs 0.2%; dyspnea 8.6% vs 9.1%; and fatigue 7.3% vs 6.6%. Conclusions: Adding cetuximab to standard CT improved overall survival over CT alone. The safety profile of CT + cetuximab was predictable and manageable. The FLEX study is the first to show a survival benefit of a targeted agent in combination with platinum-based chemotherapy across all histological subtypes in 1st-line treatment of NSCLC.
Presented at ASCO 2008: 3
Methods: In this phase III multicenter, multinational study, patients with EGFR expressing advanced NSCLC were randomized 1:1 to CT (cisplatin 80 mg/m2 d1 and vinorelbine 25 mg/m2 d1, d8 q3w) + cetuximab (400 mg/m2 initial dose, then 250 mg/m2/wk) or CT alone. The primary endpoint was overall survival (OS) and secondary endpoints included tumor response, progression-free survival (PFS), disease control,and safety.
Results: A total of 1125 patients were randomized: 557 to CT + cetuximab and 568 to CT alone. Median age: 59 (range 18–83) years; male: 70%; stage IV: 94%; adenocarcinoma: 47%; squamous cell carcinoma: 34%; ECOG performance status 0/1: 83%. Survival analysis was performed as preplanned after 868 events. OS was significantly improved in the CT + cetuximab arm vs CT (median 11.3 vs 10.1 months; HR [95% CI]: 0.871 [0.762–0.996]; p=0.0441). Results from prespecified subgroup analyses demonstrate that the addition of cetuximab provides a greater benefit in Caucasians (n=946; HR [95% CI]: 0.803 [0.694–0.928]; p=0.003) across all histologies. The response rate was significantly improved in the CT + cetuximab arm vs CT (36.3 vs 29.2%; 95% CI: 32.3–40.4 and 25.5–33.2; p=0.012). PFS was comparable in both arms whereas time to treatment failure was significantly improved with CT + cetuximab (4.2 vs 3.6 months; HR [95% CI]: 0.859 [0.760–0.970]; p=0.015). Treatment was generally well tolerated. The most common grade 3/4 adverse events (CT + cetuximab vs CT) were: neutropenia 52.7% vs 51.4%; febrile neutropenia 21.7% vs 15.5%; anemia 13.9% vs 16.7%; acne-like rash 10.4% vs 0.2%; dyspnea 8.6% vs 9.1%; and fatigue 7.3% vs 6.6%. Conclusions: Adding cetuximab to standard CT improved overall survival over CT alone. The safety profile of CT + cetuximab was predictable and manageable. The FLEX study is the first to show a survival benefit of a targeted agent in combination with platinum-based chemotherapy across all histological subtypes in 1st-line treatment of NSCLC.
Presented at ASCO 2008: 3
Datum přednesení příspěvku: 12. 9. 2008
