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)
Open accessAbstract
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. PATIENTS AND 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.
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One trial of two different doses of bevacizumab in combination with cisplatin plus gemcitabine versus placebo provided updated OS results that were not statistically significantly different.
“One trial of two different doses of bevacizumab in combination with cisplatin plus gemcitabine versus a placebo provided updated OS results (earlier results were reviewed in 2009 guideline). The results were not statistically significantly different and therefore do not provide support for changing the current recommendation.76”
From Systemic Therapy for Stage IV Non–Small-Cell Lung Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update (2015) · cites this paper as [76]
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- Authors
- Reck, M., von Pawel, J., Zatloukal, P., Ramlau, R., Gorbounova, V., Hirsh, V., Leighl, N., Mezger, J., Archer, V., Moore, N., & Manegold, C.
- Affiliations
- LungenClinic Grosshansdorf (DE)
- Charles University (CZ)
- Russian Cancer Research Center NN Blokhin (RU)
- McGill University Health Centre (CA)
- Princess Margaret Cancer Centre (CA)
- St. Vincentius-Kliniken (DE)
- Roche (United Kingdom) (GB)
- F. Hoffmann-La Roche AG (CH)
- Heidelberg University (DE)
- Corresponding author
- Reck, M.
- ORCID
- Venue
- Annals of Oncology
- Publisher
- Elsevier BV
- Published
- 2010-09
- Volume
- 21
- Issue
- 9
- Pages
- 1804-1809
- ISSN
- 0923-7534 (ISSN-L)
- PMC
- PMC2924992
- OpenAlex
- W2115330744
- Cited by
- 638
- References
- 12
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 7 · 2023: 30 · 2022: 24 · 2021: 34 · 2020: 24 · 2019: 30 · 2018: 37 · 2017: 32 · 2016: 45 · 2015: 45 · 2014: 60 · 2013: 79 · 2012: 72
- FWCI
- 66.95
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Annals of Oncology (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Hoffmann-La Roche Ltd
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
- Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
- Keywords
- bevacizumab, cisplatin, gemcitabine, non-small cell lung cancer, first-line therapy, anti-VEGF therapy, overall survival, progression-free survival, second-line therapy
- MeSH terms
- Bevacizumab, Gemcitabine, Antibodies, Monoclonal, Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Non-Small-Cell Lung, Deoxycytidine, Humans, Lung Neoplasms, Neoplasm Recurrence, Local, Neoplasm Staging, Placebos, Prognosis, Survival Rate, Carcinoma, Adenosquamous, Antibodies, Monoclonal, Humanized
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