J-L Pujol1, A Lavole2, E Quoix3, O Molinier4, P-J Souquet5, F Barlesi6, H Le Caer7, D Moro-Sibilot8, P Fournel9, J P Oster10, P Chatellain11, P Barre12, G Jeannin13, P Mourlanette14, M Derollez15, D Herman16, A Renault17, C Dayen18, P J Lamy19, A Langlais20, F Morin20, G Zalcman. 1. Pneumology Department, University Hospital, Montpellier jl-pujol@chu-montpellier.fr. 2. Pneumology Department, AP-HP Hospital Tenon, Paris. 3. Pneumology Department, University Hospital, Strasbourg. 4. Respiratory Diseases Department, Le Mans Hospital, Le Mans. 5. Pneumology Department, Pierre-Bénite Hospital, Lyon. 6. Oncology Department, Hopital Nord, Aix-Marseille University. 7. Pneumology Department, Draguignan Hospital, Draguignan. 8. Pneumology Department, University Hospital, Grenoble. 9. Oncology Department, Loire Cancer Institute, St-Priest-en-Jarez. 10. Pneumology Department, Colmar Hospital, Colmar. 11. Pneumology Department, Alpes-Léman Hospital, Ambilly. 12. Pneumology Department, Jean Rougier Hospital, Cahors. 13. Pneumology Department, Gabriel Montpied University Hospital, Clermont-Ferrand. 14. Pneumology Department, Private Hospital, Cornebarrieu. 15. Pneumology Department, Private Hospital, Maubeuge. 16. Pneumology Department, Nevers Hospital, Nevers. 17. Pneumology Department, Pau Hospital, Pau. 18. Pneumology Department, Saint-Quentin Hospital, Saint-Quentin. 19. Department of Biopathology and Oncogenetics, Regional Cancer Institute, Montpellier. 20. French Cooperative Thoracic Intergroup (IFCT), Paris.
Abstract
BACKGROUND: This randomized phase II-III trial sought to evaluate the efficacy and safety of adding bevacizumab (Bev) following induction chemotherapy (CT) in extensive small-cell lung cancer (SCLC). PATIENTS AND METHODS: Enrolled SCLC patients received two induction cycles of CT. Responders were randomly assigned 1:1 to receive four additional cycles of CT alone or CT plus Bev (7.5 mg/kg), followed by single-agent Bev until progression or unacceptable toxicity. The primary end point was the percentage of patients for whom disease remained controlled (still in response) at the fourth cycle. RESULTS: In total, 147 patients were enrolled. Partial response was observed in 103 patients, 74 of whom were eligible for Bev and randomly assigned to the CT alone group (n = 37) or the CT plus Bev group (n = 37). Response assessment at the end of the fourth cycle showed that disease control did not differ between the two groups (89.2% versus 91.9% of patients remaining responders in CT alone versus CT plus Bev, respectively; Fisher's exact test: P = 1.00). Progression-free survival (PFS) since randomization did not significantly differ, with a median PFS of 5.5 months [95% confidence interval (CI) 4.9% to 6.0%] versus 5.3 months (95% CI 4.8% to 5.8%) in the CT alone and CT plus Bev groups, respectively [hazard ratio (HR) for CT alone: 1.1; 95% CI 0.7% to 1.7%; unadjusted P = 0.82]. Grade ≥2 hypertension and grade ≥3 thrombotic events were observed in 40% and 11% of patients, respectively, in the CT plus Bev group. Serum vascular endothelial growth factor (VEGF) and soluble VEGF receptor titrations failed to identify predictive biomarkers. CONCLUSION: Administering 7.5 mg/kg Bev after induction did not improve outcome in extensive SCLC patients.
RCT Entities:
BACKGROUND: This randomized phase II-III trial sought to evaluate the efficacy and safety of adding bevacizumab (Bev) following induction chemotherapy (CT) in extensive small-cell lung cancer (SCLC). PATIENTS AND METHODS: Enrolled SCLCpatients received two induction cycles of CT. Responders were randomly assigned 1:1 to receive four additional cycles of CT alone or CT plus Bev (7.5 mg/kg), followed by single-agent Bev until progression or unacceptable toxicity. The primary end point was the percentage of patients for whom disease remained controlled (still in response) at the fourth cycle. RESULTS: In total, 147 patients were enrolled. Partial response was observed in 103 patients, 74 of whom were eligible for Bev and randomly assigned to the CT alone group (n = 37) or the CT plus Bev group (n = 37). Response assessment at the end of the fourth cycle showed that disease control did not differ between the two groups (89.2% versus 91.9% of patients remaining responders in CT alone versus CT plus Bev, respectively; Fisher's exact test: P = 1.00). Progression-free survival (PFS) since randomization did not significantly differ, with a median PFS of 5.5 months [95% confidence interval (CI) 4.9% to 6.0%] versus 5.3 months (95% CI 4.8% to 5.8%) in the CT alone and CT plus Bev groups, respectively [hazard ratio (HR) for CT alone: 1.1; 95% CI 0.7% to 1.7%; unadjusted P = 0.82]. Grade ≥2 hypertension and grade ≥3 thrombotic events were observed in 40% and 11% of patients, respectively, in the CT plus Bev group. Serum vascular endothelial growth factor (VEGF) and soluble VEGF receptor titrations failed to identify predictive biomarkers. CONCLUSION: Administering 7.5 mg/kg Bev after induction did not improve outcome in extensive SCLCpatients.