@article{f43fa0365a0e4f8e89723f3229a9011b,
title = "Italian, multicenter, phase III, randomized study of cisplatin plus etoposide with or without bevacizumab as first-line treatment in extensive-disease small-cell lung cancer: The GOIRC-AIFA FARM6PMFJM trial",
abstract = "Purpose Considering promising results in phase II studies, a randomized phase III trial was designed to assess the efficacy of adding bevacizumab to first-line cisplatin plus etoposide for treatment of extensive-disease (ED) small-cell lung cancer (SCLC). Patients and Methods Treatment-naive patients with ED-SCLC were randomly assigned to receive either cisplatin plus etoposide (arm A) or the same regimen with bevacizumab (arm B) for a maximum of six courses. In the absence of progression, patients in arm B continued bevacizumab alone until disease progression or for a maximum of 18 courses. The primary end point was overall survival (OS). Results Two hundred four patients were randomly assigned and considered in intent-to-treat analyses (103 patients in arm A and 101 patients in arm B). At a median follow-up of 34.9 months in arm A and arm B, median OS times were 8.9 and 9.8 months, and 1-year survival rates were 25% and 37% (hazard ratio, 0.78; 95% CI, 0.58 to 1.06; P = .113), respectively. A statistically significant effect of bevacizumab on OS in patients who received maintenance was seen (hazard ratio, 0.60; 95% CI, 0.40 to 0.91; P = .011). Median progression-free survival times were 5.7 and 6.7 months in arm A and arm B, respectively (P = .030). Regarding hematologic toxicity, no statistically significant differences were observed; for nonhematologic toxicity, only hypertension was more frequent in arm B (grade 3 or 4, 1.0% v 6.3% in arms A v B, respectively; P = .057). Conclusion The addition of bevacizumab to cisplatin and etoposide in the first-line treatment of ED-SCLC had an acceptable toxicity profile and led to a statistically significant improvement in progression-free survival, which, however, did not translate into a statistically significant increase in OS. Further research with novel antiangiogenic agents, particularly in the maintenance setting, is warranted. {\textcopyright} 2017 American Society of Clinical Oncology. All rights reserved.",
keywords = "bevacizumab, cisplatin, etoposide, antineoplastic agent, adult, aged, anemia, Article, cancer combination chemotherapy, cancer survival, controlled study, disease course, drug dose reduction, drug efficacy, drug withdrawal, fatigue, female, follow up, hematologic disease, human, hypertension, intention to treat analysis, Italy, leukopenia, maintenance chemotherapy, major clinical study, male, median survival time, multicenter study, multiple cycle treatment, nausea, neutropenia, overall survival, phase 3 clinical trial, priority journal, progression free survival, randomized controlled trial, small cell lung cancer, survival rate, thrombocytopenia, thrombosis, treatment outcome, vomiting, clinical trial, disease free survival, Lung Neoplasms, middle aged, Small Cell Lung Carcinoma, very elderly, Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Bevacizumab, Cisplatin, Disease-Free Survival, Etoposide, Female, Humans, Male, Middle Aged",
author = "M. Tiseo and L. Boni and F. Ambrosio and A. Camerini and E. Baldini and S. Cinieri and M. Brighenti and F. Zanelli and E. Defraia and R. Chiari and C. Dazzi and C. Tibaldi and G.M. Turolla and V. D'Alessandro and N. Zilembo and A.R. Trolese and F. Grossi and F. Riccardi and A. Ardizzoni and {GOIRC-AIFA FARM6PMFJM Trial} and Erika Rijavec",
note = "Cited By :8 Export Date: 14 July 2017 CODEN: JCOND Correspondence Address: Tiseo, M.; Oncologia Medica, Azienda Ospedaliero- Universitaria, Via Gramsci 14, Italy; email: mtiseo@ao.pr.it Chemicals/CAS: bevacizumab, 216974-75-3; cisplatin, 15663-27-1, 26035-31-4, 96081-74-2; etoposide, 33419-42-0; Bevacizumab; Cisplatin; Etoposide References: Govindan, R., Page, N., Morgensztern, D., Changing epidemiology of small-cell lung cancer in the United States over the last 30 years: Analysis of the surveillance, epidemiologic, and end results database (2006) J Clin Oncol, 24, pp. 4539-4544; Murray, N., Turrisi, A.T., III, A review of first-line treatment for small-cell lung cancer (2006) J Thorac Oncol, 1, pp. 270-278; Fr{\"u}h, M., De Ruysscher, D., Popat, S., Smallcell lung cancer (SCLC): ESMO Clinical Practice Guidelines for diagnosis treatment and follow-up (2013) Ann Oncol, 24, pp. vi99-vi105; Zhang, Y., He, J., The development of targeted therapy in small cell lung cancer (2013) J Thorac Dis, 5, pp. 538-548; Ferrara, N., Gerber, H.P., LeCouter, J., The biology of VEGF and its receptors (2003) Nat Med, 9, pp. 669-676; Lucchi, M., Mussi, A., Fontanini, G., Small cell lung carcinoma (SCLC): The angiogenic phenomenon (2002) Eur J Cardiothorac Surg, 21, pp. 1105-1110; Stefanou, D., Batistatou, A., Arkoumani, E., Expression of vascular endothelial growth factor (VEGF) and association with microvessel density in small-cell and non-small-cell lung carcinomas (2004) Histol Histopathol, 19, pp. 37-42; Spigel, D.R., Hainsworth, J.D., Yardley, D.A., Tracheoesophageal fistula formation in patients with lung cancer treated with chemoradiation and bevacizumab (2010) J Clin Oncol, 28, pp. 43-48; Horn, L., Dahlberg, S.E., Sandler, A.B., Phase II study of cisplatin plus etoposide and bevacizumab for previously untreated, extensive-stage small-cell lung cancer: Eastern Cooperative Oncology Group Study E3501 (2009) J Clin Oncol, 27, pp. 6006-6011; Spigel, D.R., Townley, P.M., Waterhouse, D.M., Randomized phase II study of bevacizumab in combination with chemotherapy in previously untreated extensive-stage small-cell lung cancer: Results from the SALUTE trial (2011) J Clin Oncol, 29, pp. 2215-2222; Spigel, D.R., Greco, F.A., Zubkus, J.D., Phase II trial of irinotecan, carboplatin, and bevacizumab in the treatment of patients with extensive-stage small-cell lung cancer (2009) J Thorac Oncol, 4, pp. 1555-1560; Ready, N.E., Dudek, A.Z., Pang, H.H., Cisplatin, irinotecan, and bevacizumab for untreated extensivestage small-cell lung cancer: CALGB 30306, a phase II study (2011) J Clin Oncol, 29, pp. 4436-4441; Wakelee, H.A., Dahlberg, S.E., Brahmer, J.R., Differential effect of age on survival in advanced NSCLC in women versus men: Analysis of recent Eastern Cooperative Oncology Group (ECOG) studies, with and without bevacizumab (2012) Lung Cancer, 76, pp. 410-415; Ready, N.E., Pang, H.H., Gu, L., Chemotherapy with or without maintenance sunitinib for untreated extensive-stage small-cell lung cancer: A randomized, double-blind, placebo-controlled phase II study-CALGB 30504 (Alliance) (2015) J Clin Oncol, 33, pp. 1660-1665; Pujol, J.L., Lavole, A., Quoix, E., 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 (2015) Ann Oncol, 26, pp. 908-914; Pujol, J.L., Breton, J.L., Gervais, R., Phase III double-blind, placebo-controlled study of thalidomide in extensive-disease small-cell lung cancer after response to chemotherapy: An intergroup study FNCLCC cleo04 IFCT 00-01 (2007) J Clin Oncol, 25, pp. 3945-3951; Lee, S.M., Woll, P.J., Rudd, R., Antiangiogenic therapy using thalidomide combined with chemotherapy in small cell lung cancer: A randomized, double-blind, placebo-controlled trial (2009) J Natl Cancer Inst, 101, pp. 1049-1057; Arnold, A.M., Seymour, L., Smylie, M., Phase II study of vandetanib or placebo in small-cell lung cancer patients after complete or partial response to induction chemotherapy with or without radiation therapy: National Cancer Institute of Canada Clinical Trials Group Study BR.20 (2007) J Clin Oncol, 25, pp. 4278-4284",
year = "2017",
doi = "10.1200/JCO.2016.69.4844",
language = "English",
volume = "35",
pages = "1281--1287",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "12",
}