Retrospective Evaluation of the Clinical and Radiographic Risk Factors Associated With Severe Pulmonary Hemorrhage in First-Line Advanced, Unresectable Non–Small-Cell Lung Cancer Treated With Carboplatin and Paclitaxel Plus Bevacizumab

Purpose Severe (grade ≥ 3) pulmonary hemorrhage (PH) in advanced non–small-cell lung cancer was observed in two prospective, randomized, phase II (N = 99) and phase III (N = 878) trials of bevacizumab plus carboplatin and paclitaxel. Retrospective case-control and cohort analyses were conducted to identify associated radiographic and clinical risk factors for PH. Patients and Methods Six patients with PH from the phase II trial, 15 potential PH patients with hemorrhage at any site from the phase III trial, and their matched controls were evaluated with review of baseline and on-treatment radiographs by an independent radiology facility, blinded to patient/control status. Patients with severe (grade ≥ 3) PH from each trial were matched with up to three controls based on sex, age group, histology (phase II), or sex and age group (phase III). Results Seven PH patients in the phase III trial were identified as severe PH. Six of the patients were early onset (occurred < 150 days of initiating bevacizumab) and one was late onset. Baseline tumor cavitation, not tumor location, was identified as the only potential risk factor for patients with early onset. Combined analysis of severe PH patients from the phase II and phase III trials (n = 13), compared with their pooled matched controls (n = 42), did not identify any additional baseline radiographic or clinical variables associated with PH. Conclusion PH was an uncommon event. Based on these analyses, baseline tumor cavitation may be a potential risk factor for PH. No other baseline clinical variables were predictive for PH although the number of events was small.