Originally published as JCO Early Release 10.1200/JCO.2009.22.0616 on September 8 2009

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Safety of Bevacizumab in Patients With Non–Small-Cell Lung Cancer and Brain Metastases

From the Multidisciplinary Thoracic Oncology Program, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC; University of Pennsylvania, Philadelphia, PA; Genentech, San Francisco, CA; and Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT.

Corresponding author: Mark A. Socinski, MD, Multidisciplinary Thoracic Oncology Program, Physician's Office Building, 170 Manning Dr, 3rd Floor, Campus Box 7305 Chapel Hill, NC 27599-7305; e-mail: Socinski{at}med.unc.edu.

Purpose Patients with non–small-cell lung cancer (NSCLC) and brain metastases have previously been excluded from trials of bevacizumab because of suspected risk of CNS hemorrhage. This phase II trial, AVF3752g (PASSPORT), specifically addressed bevacizumab safety (incidence of grade 2 CNS hemorrhage) in patients with NSCLC and previously treated brain metastases.

Patients and Methods This open-label multicenter trial for first- and second-line treatment of nonsquamous NSCLC enrolled patients with treated brain metastases. First-line patients received bevacizumab (15 mg/kg) every 3 weeks with platinum-based doublet therapy or erlotinib (at physician's decision), and second-line patients received bevacizumab with single-agent chemotherapy or erlotinib, until disease progression or death.

Results Of the 115 enrolled patients, 66 of 76 first-line patients received carboplatin-based chemotherapy; 22 of 39 second-line patients received pemetrexed, and nine of 39 received erlotinib. As of the June 23, 2008 data cut, among 106 safety-evaluable patients, median on-study duration was 6.3 months (range, 0 to 22 months), with a median of five bevacizumab cycles (range, one to 17), and no reported episodes of grade 2 CNS hemorrhage (95% CI, 0.0% to 3.3%). Of the bevacizumab-targeted adverse events reported, two were grade 5. Both were pulmonary hemorrhages, one occurring during treatment and the other occurring 6 weeks after the data cut; there was also one grade 4, nonpulmonary/non-CNS hemorrhage. Twenty-six patients (24.5%) discontinued study treatment as a result of an adverse event, and 37 (34.9%) discontinued because of disease progression.

Conclusion Addition of bevacizumab to various chemotherapy agents or erlotinib in patients with NSCLC and treated brain metastases seems to be safe and is associated with a low incidence of CNS hemorrhage.

Supported by Genentech, South San Francisco, CA.

A portion of the work described herein, from a different data cut, was presented in an abstract at the 44th Annual Meeting of the American Society of Clinical Oncology, May 30-June 3, 2008, Chicago, IL.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Clinical trial information can be found for the following: NCT00312728 [ClinicalTrials.gov] .

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