Overall survival with cisplatin-gemcitabine and bevacizumab or placebo as first-line therapy for nonsquamous non-small-cell lung cancer: results from a randomised phase III trial (AVAiL).
BACKGROUND
Bevacizumab, the anti-vascular endothelial growth factor agent, provides clinical benefit when combined with platinum-based chemotherapy in first-line advanced non-small-cell lung cancer. We report the final overall survival (OS) analysis from the phase III AVAiL trial.


METHODS
Patients (n = 1043) received cisplatin 80 mg/m(2) and gemcitabine 1250 mg/m(2) for up to six cycles plus bevacizumab 7.5 mg/kg (n = 345), bevacizumab 15 mg/kg (n = 351) or placebo (n = 347) every 3 weeks until progression. Primary end point was progression-free survival (PFS); OS was a secondary end point.


RESULTS
Significant PFS prolongation with bevacizumab compared with placebo was maintained with longer follow-up {hazard ratio (HR) [95% confidence interval (CI)] 0.75 (0.64-0.87), P = 0.0003 and 0.85 (0.73-1.00), P = 0.0456} for the 7.5 and 15 mg/kg groups, respectively. Median OS was >13 months in all treatment groups; nevertheless, OS was not significantly increased with bevacizumab [HR (95% CI) 0.93 (0.78-1.11), P = 0.420 and 1.03 (0.86-1.23), P = 0.761] for the 7.5 and 15 mg/kg groups, respectively, versus placebo. Most patients ( approximately 62%) received multiple lines of poststudy treatment. Updated safety results are consistent with those previously reported.


CONCLUSIONS
Final analysis of AVAiL confirms the efficacy of bevacizumab when combined with cisplatin-gemcitabine. The PFS benefit did not translate into a significant OS benefit, possibly due to high use of efficacious second-line therapies.
Reck
M
M
Department of Thoracic Oncology, Krankenhaus Grosshansdorf, Grosshansdorf. Electronic address: dr.martin.reck@web.de.
von Pawel
J
J
Pneumology Clinic, Asklepios Fachkliniken, München-Gauting, Germany.
Zatloukal
P
P
Department of Pneumology and Thoracic Surgery, 3rd Faculty of Medicine, Charles University, Faculty Hospital Bulovka and Postgraduate Medical School, Prague, Czech Republic.
Ramlau
R
R
Regional Center for Lung Disease, Wielkopolskie Centrum Chorob Pluc i Gruzlicy, Poznan, Poland.
Gorbounova
V
V
Russian Cancer Research Center, Moscow, Russia.
Hirsh
V
V
Medical Oncology Department, McGill University Health Centre-Royal Victoria Hospital, Montreal.
Leighl
N
N
Division of Medical Oncology, Princess Margaret Hospital, Toronto, Canada.
Mezger
J
J
Medical Department II, St Vincentius-Kliniken, Karlsruhe, Germany.
Archer
V
V
Department of Late-Stage Clinical Development, F. Hoffmann-La Roche Ltd, Welwyn Garden City, UK.
Moore
N
N
Department of Biostatistics, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Manegold
C
C
Department of Surgery, Interdisciplinary Thoracic Oncology, Heidelberg University Medical Center, Mannheim, Germany.
D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D018196:Carcinoma, Adenosquamous / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D010919:Placebos; D011379:Prognosis; D015996:Survival Rate; D000093542:Gemcitabine
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D010919:Placebos; D003841:Deoxycytidine; D000068258:Bevacizumab; D000093542:Gemcitabine