A study published in the April 18 issue of JAMA, reveals that Medicare insured non-small cell lung cancer (NSCLC) patients aged 65+, who received bevacizumab, in addition to the standard chemotherapy regimen carboplatin and paclitaxel, did not have improved survival compared to patients who received carboplatin and paclitaxel alone.

The findings of the study were presented by Deborah Schrag, M.D., M.P.H., of the Dana-Farber Cancer Institute, Boston, at a JAMA media briefing at the National Press Club.

Bevacizumab was approved by the U.S. Food and Drug Administration for the treatment of NSCLC in 2006.

The researchers said:

“A previous randomized trial demonstrated that adding bevacizumab to carboplatin and paclitaxel improved survival in advanced non-small cell lung cancer (NSCLC). However, longer survival was not observed in the subgroup of patients aged 65 years or older.

Notwithstanding the uncertainty about benefits in the population aged 65 years or older, the Centers for Medicare & Medicaid Services (CMS) has covered bevacizumab therapy for its enrollees subsequent to Food and Drug Administration (FDA) approval.

Little is known about how clinicians have interpreted efficacy studies to formulate treatment recommendations, and give that approximately two-thirds of patients with lung cancer receive their diagnosis at age 65 or older, establishing the survival advantage of bevacizumab in the Medicare population is a priority for informed decision making.”

In order to determine whether bevacizumab in addition to carboplatin-paclitaxel was linked to improved survival in the Medicare population, Dr. Schrag and her team conducted a study involving 4,168 Medicare beneficiaries aged 65+ with advances (stage IIIB or stage IV) non-squamous cell NSCLC diagnosed in 2002-2007.

The team used analytic strategies in order to address confounding and selection bias caused by the lack of treatment randomization in observational studies that may limit the ability to make valid inferences about causality.

Based on year of diagnosis and type of initial chemotherapy administered within 4 months of diagnosis, the team categorized patients into three cohorts:

  • Diagnosis in 2002-2005 and carboplatin-paclitaxel therapy.

  • Diagnosis in 2006-2007 and carboplatin-paclitaxel therapy.

  • Diagnosis in 2006-2007 and bevacizuman-carboplatin-paclitaxel therapy.

The team used various models and analyses, in order to compare overall survival and the associations between carboplatin-paclitaxel along or in addition to bevacizumab.

For patients receive carboplatin-paclitxael in 2006-2007 and 2002-2005 the team found that median overall survival was 8.9 months, and 8.0 months respectively, compared with 9.7 months for those receiving the bevacizumab combination.

One-year survival probabilities were:

  • 40.1% for carboplatin-paclitaxel in 2006-2007

  • 35.6% for carboplain-paclitaxel in 2002-2005

    • 39.6% for bevacizumab-carboplatin-paclitaxel in 2006-2007

Controlling for demographic and clinical characteristics in adjusted models, the researchers found no considerable difference in overall survival between the three cohorts.

According to the researchers, the 4 propensity score-adjusted models showed no evidence that bevacizumab-carboplatin-paclitaxel was superior to carboplatin-paclitaxel. In addition, the researchers found that neither subgroup nor sensitivity analyses linked bevacizumab with a survival advantage.

The researchers conclude:

“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.”

Written By Grace Rattue