Bevacizumab maintenance therapy extended OS in patients with NSCLC
Bevacizumab maintenance therapy contributed to an OS benefit in patients with advanced-stage non–small cell lung cancer with nonsquamous histology, according to study findings published online.
In recent randomized trials conducted in the United States and Europe, bevacizumab was evaluated combined with first-line chemotherapy in stage IIIB/IV NSCLC. In the study design of both trials, patients were offered maintenance bevacizumab (Avastin, Genentech) — after six cycles of combination therapy until disease progression or unacceptable toxicity.
In the US trial, 53% of patients continued with bevacizumab maintenance vs. 42% of patients in the European study. Based on these results, bevacizumab maintenance therapy beyond initial induction was included in the United States and European regulatory approval.
“Despite the supporting evidence and the regulatory approvals, the European Society of Medical Oncology consensus report did not include bevacizumab maintenance therapy in their recommendations,” the researchers wrote. “This exclusion suggests that the clinical utility of bevacizumab maintenance therapy requires additional supporting evidence. There are ongoing trials that compare maintenance therapy with bevacizumab or pemetrexed in advanced-stage nonsquamous disease. However, they will not address the underlying hypothesis that bevacizumab maintenance therapy prolongs patient survival without significant toxicity.”
To examine the association between bevacizumab maintenance therapy and OS in patients with advanced-stage nonsquamous NSCLC, the researchers conducted a retrospective analysis of observational data from 17 US-based community oncology practices from 2007 to Aug. 31, 2009.
Inclusion criteria for this study consisted of:
- Patients must have received first-line chemotherapy with bevacizumab for the treatment of advanced disease as part of routine clinical practice and according to institutional administration guidelines.
- Patients must be aged at least 18 years.
- Patients must have a diagnosis of stage IIIb or IV nonsquamous cell NSCLC.
- Therapy have been initiated before Aug. 31, 2009.
According to results of the analysis, 272 patients with advanced-stage NSCLC met the inclusion criteria, yet only 74 (27.2%) patients received bevacizumab maintenance therapy. Patients in the bevacizumab maintenance group tended to be younger and fitter, with a more favorable disease profile, which resulted in an improvement in the crude unadjusted OS (23.1 vs. 10.3 months; HR=0.44; 95% CI, 0.32-0.59). Landmark and propensity score analyses maintained the finding of a reduced risk of death with bevacizumab maintenance therapy (HR=0.52; 95% CI, 0.37-0.73 for landmark analyses and HR=0.70; 95% CI, 0.39-1.28 for propensity score analyses).
Rationale for not commencing maintenance therapy were available for 179 (90.4%) of 198 patients and included: lack of response to induction therapy (15.2%); toxicity during the induction phase (10.6%); not considered in the initial management plan (10.1%); switched to another therapy (11.1%); early patient death (7.1%); poor performance status (5.6%); patient refusal (5.1%); other medical or treatment history (5.1%); other undisclosed reasons (20.7%).
“Despite having received US Food and Drug Administration approval, not all patients who were eligible received bevacizumab maintenance therapy in our cohort,” the researchers wrote. “The reasons behind this observation need further exploration. There was also a higher propensity to use this treatment in patients with a better risk as well as in certain geographic regions of the United States. Regardless of these variations, the statistical and sensitivity analysis suggested that bevacizumab maintenance therapy was associated with a survival benefit in our cohort of patients with nonsquamous NSCLC.”
Disclosure: The researchers report employment-relationships and financial support from Genentech.