Carboplatin and paclitaxel with vs without bevacizumab in older patients with advanced non-small cell lung cancer

Abstract

Context: 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.

Objective: To examine whether adding bevacizumab to carboplatin and paclitaxel chemotherapy is associated with improved survival in older patients with NSCLC.

Design, setting, and participants: Retrospective cohort study of 4168 Medicare beneficiaries aged 65 years or older with stage IIIB or stage IV non-squamous cell NSCLC diagnosed in 2002-2007 in a Surveillance, Epidemiology, and End Results (SEER) region. Patients were categorized 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 Cox proportional hazards models and propensity score analyses including information about patient characteristics recorded in SEER-Medicare.

Main outcome measure: Overall survival measured from the first date of chemotherapy treatment until death or the censoring date of December 31, 2009.

Results: The median survival estimates were 9.7 (interquartile range [IQR], 4.4-18.6) months for bevacizumab-carboplatin-paclitaxel, 8.9 (IQR, 3.5-19.3) months for carboplatin-paclitaxel in 2006-2007, and 8.0 (IQR, 3.7-17.2) months for carboplatin-paclitaxel in 2002-2005. One-year survival probabilities were 39.6% (95% CI, 34.6%-45.4%) for bevacizumab-carboplatin-paclitaxel vs 40.1% (95% CI, 37.4%-43.0%) for carboplatin-paclitaxel in 2006-2007 and 35.6% (95% CI, 33.8%-37.5%) for carboplatin-paclitaxel in 2002-2005. Neither multivariable nor propensity score-adjusted Cox models demonstrated a survival advantage for bevacizumab-carboplatin-paclitaxel compared with carboplatin-paclitaxel cohorts. In propensity score-stratified models, the hazard ratio for overall survival for bevacizumab-carboplatin-paclitaxel compared with carboplatin-paclitaxel in 2006-2007 was 1.01 (95% CI, 0.89-1.16; P = .85) and compared with carboplatin-paclitaxel in 2002-2005 was 0.93 (95% CI, 0.83-1.06; P = .28). The propensity score-weighted model and propensity score-matching model similarly failed to demonstrate a statistically significant superiority for bevacizumab-carboplatin-paclitaxel. Subgroup and sensitivity analyses for key variables did not change these findings.

Conclusion: Adding bevacizumab to carboplatin and paclitaxel chemotherapy was not associated with better survival among Medicare patients with advanced NSCLC.

Figure 1

Cohort Assembly: Medicare Enrollees Diagnosed with Stage IIIB/IV Non-Squamous NSCLC in 2002–2007 Treated with Either Paclitaxel–Carboplatin Alone or with Bevacizumab Abbreviations: NSCLC, non-small-cell lung cancer; AJCC, American Joint Committee on Cancer; HMO, health maintenance organization; BCP, bevacizumab-carboplatin-paclitaxel; CP, carboplatin-paclitaxel. ^a The inclusion criteria were applied sequentially as listed. ^b 19 patients treated with BCP in 2005 were included in the BCP group.

Figure 2

Kaplan-Meier Survival Curves for Medicare Beneficiaries Diagnosed with Advanced Non-Squamous Non-Small-Cell Lung Cancer, by Year of Diagnosis and First-Line Chemotherapy Administration with or without Bevacizumab [Table: see text]