Safety of bevacizumab in patients with non-small-cell lung cancer and brain metastases.
OBJECTIVE
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 > or = 2 CNS hemorrhage) in patients with NSCLC and previously treated brain metastases.


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 > or = 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.


CONCLUSIONS
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.
Socinski
Mark A
MA
Multidisciplinary Thoracic Oncology Program, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599-7305, USA. Socinski@med.unc.edu
Langer
Corey J
CJ
Huang
Jane E
JE
Kolb
Margaret M
MM
Compton
Peter
P
Wang
Lisa
L
Akerley
Wallace
W
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000556:secondary; D016190:Carboplatin / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000556:secondary; D000069347:Erlotinib Hydrochloride; D005260:Female; D005971:Glutamates / Q000627:therapeutic use; D006147:Guanine / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000068437:Pemetrexed; D011799:Quinazolines / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D005971:Glutamates; D011799:Quinazolines; D000068437:Pemetrexed; D000068258:Bevacizumab; D006147:Guanine; D016190:Carboplatin; D000069347:Erlotinib Hydrochloride