Randomized phase II–III study of bevacizumab in combination with chemotherapy in previously untreated extensive small-cell lung cancer: results from the IFCT-0802 trial

• Published in: Annals of oncology Vol. 26; no. 5; pp. 908 - 914
• Main Authors: Pujol, J.-L., Lavole, A., Quoix, E., Molinier, O., Souquet, P.-J., Barlesi, F., Le Caer, H., Moro-Sibilot, D., Fournel, P., Oster, J.P., Chatellain, P., Barre, P., Jeannin, G., Mourlanette, P., Derollez, M., Herman, D., Renault, A., Dayen, C., Lamy, P.J., Langlais, A., Morin, F., Zalcman, G., Westeel, V., Poudenx, M., Mazieres, J., Martinet, Y., Gury, J-P., Baize, N., Dumont, P., Vaylet, F., Foucher, P., Dauba, J., Tredaniel, J., Laize, H., Petit, L., Coëtmeur, D., Doubre, H., Pichon, E., Schneider, S., Goutorbe, F., Gervais, R., Zaegel, M., Dehette, S., Coudert, B., Duhamel, J-P., Dixmier, A., Thiberville, L., Deguiral, P., Monnot, H., Romand, P., Berard, H., Raspaud, C.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-05-2015; Elsevier
• Subjects: Adult; Aged; Angiogenesis Inhibitors - adverse effects; Angiogenesis Inhibitors - therapeutic use; anti-angiogenesis therapy; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; bevacizumab; Bevacizumab - adverse effects; Bevacizumab - therapeutic use; Cancer; chemotherapy; Cisplatin - therapeutic use; Cyclophosphamide - therapeutic use; Disease Progression; Disease-Free Survival; Epirubicin - therapeutic use; Etoposide - therapeutic use; Female; France; Humans; Induction Chemotherapy; Kaplan-Meier Estimate; Life Sciences; Lung Neoplasms - drug therapy; Lung Neoplasms - mortality; Lung Neoplasms - pathology; Male; Middle Aged; Proportional Hazards Models; Risk Factors; Small Cell Lung Carcinoma - drug therapy; Small Cell Lung Carcinoma - mortality; Small Cell Lung Carcinoma - pathology; small-cell lung cancer; Time Factors; Treatment Outcome; Young Adult; France; bevacizumab; anti-angiogenesis therapy; small-cell lung cancer; chemotherapy
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/annonc/mdv065

IFCT study administering 7.5 mg/kg Bevacizumab plus chemotherapy after chemotherapy induction did not improve outcomes in extensive SCLC patients.
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).
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.
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.
Administering 7.5 mg/kg Bev after induction did not improve outcome in extensive SCLC patients.