Data from a study ( E4599 ) of Bevacizumab ( Avastin ) plus Paclitaxel and Carboplatin in first-line non-squamous, non-small cell lung cancer ( NSCLC ) showed the study met its primary efficacy endpoint of improving overall survival.

Bevacizumab is a therapeutic antibody designed to inhibit Vascular Endothelial Growth Factor ( VEGF ), a protein that plays an important role in tumor angiogenesis and maintenance of existing tumor vessels.

An interim analysis of this study demonstrated that patients receiving Bevacizumab plus Paclitaxel and Carboplatin had a 30 percent improvement in overall survival ( or a hazard ratio of 0.77, which can also be referred to as a 23 percent reduction in the risk of death ), compared to patients who received chemotherapy alone.

This study showed that median survival of patients treated with Bevacizumab plus chemotherapy was 12.5 months compared to 10.2 months for patients treated with chemotherapy alone.

“ The results of this Phase III study reveal, for the first time, an improvement in survival with the addition of a targeted biologic agent to standard chemotherapy in this patient population, and the first time median survival has been extended beyond one year in advanced lung cancer,” said Alan B Sandler, of Vanderbilt University Medical Center in Nashville. “ We also observed improvements in other measures of patient benefit, including progression-free survival and tumor response rate. ”

This study showed a 61 percent improvement in progression-free survival ( or a hazard ratio of 0.62, which can also be referred to as a 38 percent reduction in the risk of progression ).
Median progression-free survival was 6.4 months for patients treated with Bevacizumab plus chemotherapy, compared to 4.5 months for patients treated with chemotherapy alone.

The response rate in patients with measurable disease was 27 percent ( 97/357 ) in the group receiving Bevacizumab plus chemotherapy, compared to 10 percent ( 35/350 ) in the group receiving chemotherapy alone.

In previous clinical experience with Avastin in combination with Paclitaxel and Carboplatin in NSCLC, patients with a specific type of NSCLC called squamous cell carcinoma had a higher risk of experiencing life-threatening or fatal pulmonary bleeding.
These patients were excluded from this Phase III study and the rate of life-threatening or fatal pulmonary bleeding in patients treated with Avastin was substantially reduced from prior clinical studies.

A preliminary assessment of adverse events by the investigators showed that Grade 3/4/5 bleeding occurred in 4.5 percent of patients in the Avastin plus chemotherapy arm, compared to 1 percent of patients in the chemotherapy alone arm.

Treatment-related deaths occurred at a rate of 2 percent ( 8/420 ) in the Avastin plus chemotherapy arm, compared to less than 1 percent ( 2/427 ) in the chemotherapy alone arm.
Fatal ( Grade 5 ) hemoptysis occurred at a rate of 1 percent ( 5/420 ) in the Avastin plus chemotherapy arm.

The preliminary safety assessment showed that the most common adverse events were neutropenia, hypertension and thrombotic events.
Grade 3/4 neutropenia occurred in 24 percent of patients treated with Avastin plus chemotherapy and 16 percent of patients who received chemotherapy alone.
Hypertension occurred in 6 percent of patients who received Avastin plus chemotherapy and 1 percent of patients who received chemotherapy alone.
Grade 3/4 venous thrombosis occurred in 4 percent of patients treated with Avastin plus chemotherapy, compared with 3 percent of patients treated with chemotherapy alone.
Grade 3/4 arterial thrombosis occurred in 2 percent of patients treated with Avastin plus chemotherapy, compared with 1 percent in patients treated with chemotherapy alone.

The trial was sponsored by the National Cancer Institute ( NCI ), part of the National Institutes of Health ( NIH ), under a Cooperative Research and Development Agreement between NCI and Genentech, and conducted by a network of researchers led by the Eastern Cooperative Oncology Group ( ECOG ).

Source: 41st Annual Meeting of the American Society of Clinical Oncology ( ASCO ), 2005


XagenaMedicine2005