(ChemotherapyAdvisor) – The addition of bevacizumab to carboplatin and paclitaxel did not improve overall survival in Medicare patients with advanced non–small-cell lung cancer (NSCLC) and should not be considered standard of care for this population, according to a study in the April 18 issue of JAMA, a theme issue on comparative effectiveness research.

“A previous randomized trial demonstrated that adding bevacizumab to carboplatin and paclitaxel improved survival in advanced NSCLC,” the investigators noted. “However, longer survival was not observed in the subgroup of patients aged 65 years or older.” The Centers for Medicare & Medicaid Services has covered bevacizumab therapy for its enrollees subsequent to Food and Drug Administration approval. “…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,” they noted.

The retrospective cohort study categorized 4,168 Medicare beneficiaries aged 65 years or older with stage IIIB/IV nonsquamous NSCLC into 3 cohorts based on year of diagnosis and type of initial chemotherapy administered within 4 months of diagnosis: 2006-2007 and bevacizumab-carboplatin-paclitaxel; 2006-2007 and carboplatin paclitaxel; or 2002-2005 and carboplatin-paclitaxel therapy. The patients were diagnosed in 2002-2007 in a Surveillance, Epidemiology, and End Results (SEER) region.

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For bevacizumab-carboplatin-paclitaxel, median survival estimate was 9.7 months compared with 8.9 months for carboplatin paclitaxel in 2006-2007, and 8.0 months for carboplatin-paclitaxel in 2002-2005. At 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.

The hazard ratio for overall survival for bevacizumab-carboplatin-paclitaxel vs. carboplatin-paclitaxel in 2006-2007 was 1.01 (P=.85) and compared with carboplatin paclitaxel in 2002-2005 was 0.93 (P=.28). None of the 4 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.

“In the future, for malignancies like NSCLC that disproportionately affect elderly patients or where the CMS covers a large proportion of treatment costs, negotiations with pharmaceutical sponsors of pivotal trials might mandate adequate representation of elderly patients and/or preplanned subgroup analyses relevant to the Medicare population. Absent this information, clinicians will need to rely on efficacy data from subgroup analysis of randomized trials, observational data such as this report, and their clinical judgment to make treatment recommendations. 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. Clinicians should exercise caution in making treatment recommendations and should use bevacizumab judiciously for their older patients,” the authors conclude.