Bevacizumab in Non-Small Cell Lung Cancer

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The FDA approved bevacizumab in combination with carboplatin and paclitaxel as a frontline treatment for patients with non-squamous non-small cell lung cancer (NSCLC) in October 2006. The approval was based on a 2-month extension in overall survival (OS) experienced by patients enrolled in the E4599 trial who received bevacizumab plus chemotherapy versus chemotherapy alone.

Bevacizumab is an effective therapy for patients with non-squamous NSCLC, but should not be utilized in patients with squamous histology, Mark Socinski, MD, explains. Patients with squamous cell NSCLC were excluded from the E4599 study, based on an earlier experience seen among 13 patients with this histology enrolled in a phase II study. In these patients, 4 experienced life-threatening or fatal hemoptysis when treated with bevacizumab plus chemotherapy.

Outside of histology, the presence of gross hemoptysis is considered a contraindication for bevacizumab. One of the leading challenges in clinical practice is evaluating hemoptysis, Socinski notes. In general, if there is >1/2 teaspoon of red blood expelled during coughing, bevacizumab should not be administered.

Age and performance status (PS) should also be considered prior to administering bevacizumab, Socinski notes. A survival benefit has not been clearly demonstrated in patients older than 70 or 75 years. The median age of patients in the E4599 trial was 63 years. Additionally, older age groups seem to experience a higher incidence of adverse events with bevacizumab, Socinski notes. Additionally, bevacizumab has largely been studied in patients with ECOG PS 0 to 1, with limited data available for patients with PS2. Given this lack of clear data, bevacizumab should be avoided in patients with a higher PS, Socinski notes.

One of the more interesting observations made regarding bevacizumab concerns its potential utility in patients with EGFR-mutated NSCLC, Socinski notes. In a randomized trial, 154 Japanese patients with EGFR-mutated NSCLC received erlotinib or the combination of erlotinib and bevacizumab. There was a strikingly positive effect with bevacizumab, particularly in median progression-free survival (PFS), Socinski notes. In the study, the median PFS with the combination was 16.0 versus 9.7 months with erlotinib alone (HR = 0.54; P = .0015).

The phase II trial sponsored by the Academic and Community Cancer Research United is exploring erlotinib with or without bevacizumab in patients with metastatic EGFR-mutant NSCLC. The target enrollment for the study is 118 patients (NCT01532089).