Phase II Study of Topotecan and Bevacizumab in Advanced, Refractory Non–Small-Cell Lung Cancer

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Second-line therapies for non–small-cell lung cancer (NSCLC) provide modest disease control. Weekly topotecan in combination with bevacizumab was evaluated in advanced, refractory NSCLC. Median progression-free survival was 5.1 months and overall survival was 11.5 months. Based on its favorable disease control rate and tolerable side effect profile, this combination should be further evaluated in refractory NSCLC.


This clinical trial evaluated whether topotecan in combination with bevacizumab improved progression-free survival (PFS) in patients with advanced, refractory non–small-cell lung cancer in a second-line setting.

Patient and Methods:

Patients aged 18 years old and older received topotecan (4.0 mg/m2) on days 1, 8, and 15, and bevacizumab (10 mg/kg) on days 1 and 15 as intravenous infusions on a 28-day treatment cycle. Available tumor specimens were analyzed for ISG15 gene expression as a biomarker of response to topotecan.


Forty-two patients were enrolled in the study, with a median age of 62.5 years and a median of 3 (range, 1-7) prior treatment regimens. Almost half (n = 18, 42.9%) of the patients received prior bevacizumab therapy. PFS was 5.1 months (95% CI, 3.7-7.8 months), and overall survival was 11.5 months (95% CI, 6.8-15.5 months). Response rates were as follows: 14.3% partial response, 54.8% stable disease, and 28.6% progressive disease. Hematologic toxicities included grade 3 thrombocytopenia (n = 7, 16.7%), neutropenia (n = 4, 9.5%), and anemia (n = 2, 4.8%). One toxic death occurred due to pulmonary hemorrhage, and one patient experienced a grade 4 pulmonary embolism. Grade 3 nonhematologic adverse events were uncommon (< 8%). There was a trend for improved median PFS, 3.5 months vs. 1.8 months (P = .26), in patients with high ISG15 expression.


Bevacizumab in combination with topotecan as a salvage therapy for metastatic non–small-cell lung cancer is well tolerated and is worthy of further investigation.

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