Treatment with bevacizumab was associated with an absolute risk
reduction for 1-year death and 6-month progression, but those improvements were
accompanied by an increase in several serious adverse events, results of the
ECOG-E4599 and AVAiL trials showed.
Researchers used a random effect model to conduct pooled analysis of the
two trials. Results were then summarized as number-needed-to-treat and
number-needed-to-harm. Patients in ECOG-E4599 were randomly assigned to
paclitaxel (200 mg/m2) plus carboplatin (area under the curve 6)
alone, or with 15 mg/kg
bevacizumab (Avastin, Genentech/Roche). Patients in AVAiL
were randomly assigned to 80 mg/m2 cisplatin and gemcitabine
(Gemzar, Eli Lilly) 1,250 mg/m2 plus 7.5 mg/kg bevacizumab or 15
mg/kg bevacizumab or placebo.
There were 1,576 patients with advanced, chemotherapy-naive,
non-squamous non–small cell lung cancer included in the
primary analysis and 1,921 included in the secondary analysis. The primary
analysis included only the patients treated with 15 mg/kg bevacizumab in the
experimental arm, whereas the secondary, descriptive analysis included the
patients treated with bevacizumab 15 mg/kg or those treated with 7.5 mg/kg
bevacizumab in the experimental arm.
The absolute reduction in risk for 1-year death was 3.3% (95% CI,
–6.5 to 13.2) with a number-needed-to-treat of 30. The absolute risk
reduction for 6-month progression was 15.2% (95% CI, 0.07-29.6) with a
number-needed-to-treat of six. The number-needed-to-treat favored bevacizumab
in both cases.
The absolute risk for treatment-related death was 2.4% (95% CI,
0.8-3.9); 6.6% for hypertension (95% CI, 4.6-8.6); 2.1% for proteinuria (95%
CI, 0.3-3.8); 7.3% for neutropenia (95% CI, 3.2-11.4); and 1.5% for
thrombocytopenia (95% CI, 0.2-2.7).
Researchers did not observe a dose response in the efficacy and the
safety analysis when all the patients treated with bevacizumab were included
into the pooled analysis.