BRIDGE: an open-label phase II trial evaluating the safety of bevacizumab + carboplatin/paclitaxel as first-line treatment for patients with advanced, previously untreated, squamous non-small cell lung cancer.
BACKGROUND
Patients with predominantly squamous non-small cell lung cancer (NSCLC) have been generally excluded from studies of bevacizumab treatment, because squamous histology was identified as a possible risk factor for severe (grade ≥3) pulmonary hemorrhage (PH) in a phase II study. BRIDGE was designed to determine whether delaying initiation of bevacizumab treatment and selecting patients without baseline risk factors for PH would lower the incidence of severe PH among patients with squamous NSCLC.


METHODS
Patients in this open-label, single-arm study were treated with carboplatin/paclitaxel for two cycles, followed by carboplatin/paclitaxel and bevacizumab in cycles 3 to 6, followed by bevacizumab until progression or unacceptable toxicity. Eligible patients had stage IIIb, stage IV, or recurrent squamous NSCLC. The primary end point was incidence of grade ≥3 PH.


RESULTS
Grade ≥3 PH occurred in 1 of 31 patients who received ≥1 dose of bevacizumab: estimated incidence was 3.2% (90% confidence interval 0.3-13.5%). The patient experienced grade 3 PH, discontinued from the study, then experienced grade 4 PH 10 days later, and died of progressive disease. No other serious bleeding events occurred. Nine patients (29.0%) experienced grade 3 adverse events, including five with hypertension; five patients experienced grade 4 adverse events (dyspnea, PH, basal ganglia infarction, cerebral ischemia, and pain). Median progression-free survival was 6.2 months (95% confidence interval 5.32-7.62 months).


CONCLUSIONS
The incidence of grade ≥3 PH was 3.2% (one patient). No new safety signals were identified. Although the rate of PH was low, the number of patients in this study was also low. Treatment of squamous NSCLC with bevacizumab should be considered experimental.
Sarah Cannon Research Institute, Nashville, Tennessee 37203, USA. John.Hainsworth@HCAHealthcare.com
John D
JD
Hainsworth
Liang
L
Fang
Jane E
JE
Huang
David
D
Karlin
Kenneth
K
Russell
Leonardo
L
Faoro
Christopher
C
Azzoli
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000556:secondary; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D010865:Pilot Projects; D012307:Risk Factors; D015996:Survival Rate; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D016190:Carboplatin; D017239:Paclitaxel