PIII trial shows life extension for patients with NSCLC

Biotech giants Genentech and Roche have announced that an interim analysis of a Phase III study of Avastin (bevacizumab) plus paclitaxel and carboplatin chemotherapies in first-line non-squamous, non-small cell lung cancer (NSCLC) met its primary efficacy endpoint of improving overall survival, or a reduction in the risk of death, compared with chemotherapy alone.

The trial was sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health, 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).

'These results represent the first study combining a targeted biologic therapy with chemotherapy to show an overall survival improvement in the first-line NSCLC setting, and the first time that any treatment has improved upon the standard, two-drug chemotherapy regimen in this disease,' said Dr Hal Barron, Genentech senior vice president, development and chief medical officer. 'We would like to thank our collaborators at NCI and ECOG for their work on this study, as well as the many patients and their families who made the decision to participate in this study. We plan to share these data with the FDA to discuss the possibility of filing a supplemental Biologics License Application for Avastin plus chemotherapy in first-line NSCLC.'

This is the first Phase III study to evaluate the therapeutic antibody Avastin in combination with chemotherapy in NSCLC. This was a randomised, controlled, multicentre trial that enrolled 878 patients with previously-untreated advanced NSCLC. The patients enrolled in this trial were randomised to receive treatment with paclitaxel and carboplatin chemotherapies with or without Avastin.

Adverse events

In previous clinical experience with Avastin in combination with paclitaxel and carboplatin in NSCLC, life-threatening or fatal pulmonary bleeding was identified as a severe adverse event apparently unique to this disease. Certain characteristics, including any significant pulmonary bleeding prior to receiving treatment with Avastin or the presence of a specific type of NSCLC called squamous cell carcinoma appeared to predispose patients to experiencing this adverse event. Patients with these characteristics were excluded from this Phase III study and the rate of life-threatening or fatal pulmonary bleeding was substantially reduced from prior clinical studies. However, some patients did experience fatal pulmonary bleeding in this trial and this event was more common in the patient group that received Avastin in combination with chemotherapy than in the patient group that received chemotherapy only. Other adverse events observed in this study were similar to those identified in previous Phase II and Phase III studies of Avastin.

About Avastin

Avastin is a therapeutic antibody designed to inhibit Vascular Endothelial Growth Factor (VEGF), a protein that plays an important role in tumour angiogenesis and maintenance of existing tumour vessels. By binding to VEGF, Avastin is designed to interfere with the blood supply to tumours, a process that is critical to tumour growth and metastasis.