An interim analysis of a Phase III study of Avastin ( Bevacizumab ) in combination with Paclitaxel and Carboplatin in advanced, non-small cell lung cancer ( NSCLC ) met its primary efficacy endpoint of improving overall survival, or a reduction in the risk of death, compared to chemotherapy alone.
Non-small cell lung cancer is the most common form of lung cancer.
Avastin is a recombinant humanized antibody to Vascular Endothelial Growth Factor ( VEGF ), designed to bind to and inhibit VEGF, a protein that plays a critical role in tumor angiogenesis ( the formation of new blood vessels to the tumor ).
The Phase III trial investigated the use of Avastin in combination with a Platinum-based chemotherapy ( Paclitaxel and Carboplatin ) in patients who had not received any previous treatment.
The randomised, controlled, multicenter study enrolled 878 patients with advanced NSCLC.
It was conducted by a network of Researchers led by the Eastern Cooperative Oncology Group ( ECOG ).
Patients were randomized to receive treatment with Paclitaxel and Carboplatin with or without Avastin.
Avastin was administered at 15 mg/kg every three weeks.
Paclitaxel and Carboplatin were also administered every three weeks.
The treatment in both arms was repeated every three weeks for up to six courses in the absence of disease progression or unacceptable toxicity.
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.
The FDA approved Avastin on February, 2004 as a first-line treatment for metastatic colorectal cancer in combination with intravenous 5-FU-based chemotherapy.
Approval was based on data from two trials.
The pivotal trial was a large, placebo-controlled, randomized study of 925 patients that demonstrated a prolongation in the median survival of patients treated with Avastin plus the IFL ( 5-FU/Leucovorin/CPT-11 ) chemotherapy regimen by approximately five months, compared to patients treated with the IFL chemotherapy regimen alone ( 20.3 months versus 15.6 months ).
In addition, this study demonstrated an improvement in progression-free survival of more than four months (10.6 months in the Avastin/IFL arm compared to 6.4 months in the IFL-alone arm ).
Genentech and Roche are investigating the use of Avastin in advanced colorectal cancer with other chemotherapies, and in other cancers such as pancreatic cancer, ovarian cancer, renal cell carcinoma.
Source: Genentech, 2005