Safety and efficacy of first-line bevacizumab-based therapy in advanced non-squamous non-small-cell lung cancer (SAiL, MO19390): a phase 4 study

• Published in: The lancet oncology 2010-08, Vol.11 (8), p.733-740
• Main Authors: Crinò, Lucio, Prof, Dansin, Eric, MD, Garrido, Pilar, MD, Griesinger, Frank, Prof, Laskin, Janessa, MD, Pavlakis, Nick, MBBS, Stroiakovski, Daniel, Prof, Thatcher, Nick, Prof, Tsai, Chun-Ming, Prof, Wu, Yi-long, Prof, Zhou, Caicun, Prof
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Angiogenesis Inhibitors - administration & dosage; Angiogenesis Inhibitors - adverse effects; Angiogenesis Inhibitors - therapeutic use; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - pathology; Drug-Related Side Effects and Adverse Reactions; Female; Hematology, Oncology and Palliative Medicine; Humans; Intention to Treat Analysis; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Male; Middle Aged; Survival Analysis
• ISSN: 1470-2045; 1474-5488
• DOI: 10.1016/S1470-2045(10)70151-0

Summary Background Results of two phase 3 trials have shown first-line bevacizumab in combination with chemotherapy improves clinical outcomes in patients with advanced or recurrent non-squamous non-small-cell lung cancer (NSCLC). The SAiL ( MO19390 ) study was undertaken to assess the safety and efficacy of first-line bevacizumab combined with standard chemotherapy regimens in clinical practice. Methods Between August, 2006, and June, 2008, patients with untreated locally advanced, metastatic, or recurrent non-squamous NSCLC were recruited to this open-label, single group, phase 4 study from centres in 40 countries. Eligible patients had histologically or cytologically documented inoperable, locally advanced, metastatic, or recurrent disease (stage IIIB–IV); an Eastern Cooperative Oncology Group performance status of 0–2; and adequate haematological, hepatic, and renal function. Patients received bevacizumab (7·5 or 15 mg/kg every 3 weeks) plus standard chemotherapy for up to six cycles, followed by single-agent bevacizumab until disease progression. The primary endpoint was safety; analysis was by intention to treat (ITT). This study is registered with ClinicalTrials.gov , number NCT00451906. Findings At the final data cutoff (July 24, 2009), an ITT population of 2212 patients was assessed. The incidence of clinically significant (grade ≥3) adverse events of special interest was generally low; thromboembolism occurred in 172 (8%) patients, hypertension in 125 (6%), bleeding in 80 (4%), proteinuria in 67 (3%), and pulmonary haemorrhage in 15 (1%). 57 (3%) patients died because of these adverse events, with thromboembolism (26 patients, 1%) and bleeding (17, 1%) as the most common causes. The most common grade 3 or higher serious adverse events deemed by investigators to be associated with bevacizumab were pulmonary embolism (28 patients; 1%) and epistaxis, neutropenia, febrile neutropenia, and deep vein thrombosis (all of which occurred in 13 patients [1%]). Bevacizumab was temporarily interrupted after 28 (2%) of 1347 bleeding events and 72 (7%) of 1025 hypertension events, and permanently discontinued after 110 (8%) bleeding events and 40 (4%) hypertension events. No new safety signals were reported. Interpretation Our results confirm the manageable safety profile of first-line bevacizumab in combination with various standard chemotherapy regimens for treatment of advanced non-squamous NSCLC. Funding F Hoffmann-La Roche Ltd.