Adding bevacizumab to chemotherapy in elderly patients with advanced non-squamous cell NSCLC not associated with improved survival
Adequate representation of elderly patients in pivotal trials and pre-planned subgroup analyses needed
A new analysis shows that bevacizumab added to the standard chemotherapy regimen carboplatin and paclitaxel did not have improved survival in patients age 65 years and older compared to patients who received the standard treatment of carboplatin and paclitaxel alone, according to a study in the April 18 issue of JAMA, a theme issue on comparative effectiveness research. A previous randomised trial demonstrated that adding bevacizumab to carboplatin and paclitaxel improved survival in patients with advanced non-small cell lung cancer (NSCLC), and this drug regimen was approved by the FDA in 2006.
Dr Deborah Schrag of the Dana-Farber Cancer Institute, Boston, USA and colleagues conducted a study in patients aged 65 years or older to examine whether adding bevacizumab to carboplatin/paclitaxel was associated with improved survival in the Medicare population. According to the authors, little is known about how clinicians have interpreted efficacy studies to formulate treatment recommendations, and given that approximately two-thirds of patients with lung cancer receive their diagnoses at age 65 years or older, establishing the survival advantage of bevacizumab in the Medicare population is a priority for informed decision making.
Malignancy that disproportionally affect elderly patients
Dr. Schrag and colleagues used analytic strategies to address confounding (factors that can influence outcomes) and selection bias caused by the lack of treatment randomisation in observational studies that may limit the ability to make valid inferences about causality. The study included 4168 Medicare beneficiaries ages 65 years or older with advanced, stage IIIB or stage IV, non-squamous cell NSCLC diagnosed in 2002-2007. Patients were categorised into 3 cohorts based on diagnosis year and type of initial chemotherapy administered within 4 months of diagnosis: (1) diagnosis in 2006-2007 and bevacizumab/carboplatin/paclitaxel therapy; (2) diagnosis in 2006-2007 and carboplatin/paclitaxel therapy; or (3) diagnosis in 2002-2005 and carboplatin/paclitaxel therapy. The associations between carboplatin/paclitaxel with vs. without bevacizumab and overall survival were compared using various models and analyses.
The researchers found that the median overall survival was 9.7 months for patients receiving the bevacizumab combination compared with 8.9 months for those receiving carboplatin/paclitaxel in 2006-2007, and 8.0 months for those receiving carboplatin/paclitaxel in 2002-2005. The 1-year survival probabilities were 39.6% for bevacizumab/carboplatin/paclitaxel vs. 40.1% for carboplatin/paclitaxel in 2006-2007 and 35.6% for carboplatin/paclitaxel in 2002-2005. Controlling for demographic and clinical characteristics in adjusted models, the authors did not find a significant difference in overall survival between patients treated with bevacizumab and those treated only with carboplatin/paclitaxel in either 2006-2007 or 2002-2005.
None of the four propensity score-adjusted models demonstrated any evidence to support the superiority of bevacizumab/carboplatin/paclitaxel to carboplatin/paclitaxel. Also, neither subgroup nor sensitivity analyses changed their finding that bevacizumab was not associated with a survival advantage.
The authors concluded that given that neither subgroup analyses from efficacy studies nor observational data analyses identify a benefit for adding bevacizumab to standard carboplatin/paclitaxel therapy, bevacizumab should not be considered standard of care in this context.
Project support for this analysis was obtained from the Agency for Healthcare Research and Quality (AHRQ) as part of the Developing Evidence to Inform Decisions about Effectiveness (DEcIDE) programme and from the National Cancer Institute (USA).
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