Avastin® (bevacizumab) in Lung Cancer
Full Prescribing Information, including Boxed Warnings.
Avastin was the first anti-angiogenesis therapy approved by the U.S. Food and Drug Administration (FDA). It was approved in combination with carboplatin and paclitaxel for the first-line treatment of patients with unresectable, locally advanced, recurrent or metastatic non-squamous, non-small cell lung cancer (NSCLC) in October 2006.
Avastin "First" in Metastatic NSCLC Avastin, in combination with chemotherapy, is the first drug in more than 10 years to improve upon standard first-line treatment, and the first targeted therapy ever to extend overall median survival beyond one year in a large, randomized clinical study.
Proposed Mechanism of Action Avastin is a therapeutic antibody (not chemotherapy) specifically designed to bind to and inhibit the vascular endothelial growth factor (VEGF) protein, a potent source of angiogenesis. Angiogenesis is a process that connects tumors to the blood supply.3 By inhibiting VEGF, Avastin may interfere with the blood supply to a tumor, which is thought to be critical to a tumor's ability to grow and spread in the body (metastasize). The effects of Avastin on tumor blood vessels may also enhance the delivery of chemotherapy drugs to the cancer.4-6
Clinical Trial Data First-Line Treatment in Metastatic NSCLC The FDA approval for this indication was based on results from E4599, a randomized, controlled, multi-center trial that enrolled 878 patients with unresectable, locally advanced, recurrent or metastatic non-squamous NSCLC. Results showed that patients receiving Avastin plus paclitaxel and carboplatin chemotherapy had a 25 percent improvement in overall survival, the trial's primary endpoint, compared to patients who received paclitaxel and carboplatin alone (based on a hazard ratio of 0.80). One-year survival was 51 percent in the Avastin plus chemotherapy arm versus 44 percent in the chemotherapy-alone arm. Median survival of patients treated with Avastin plus chemotherapy was 12.3 months, compared to 10.3 months for patients treated with chemotherapy alone.1
The National Comprehensive Cancer Network (NCCN) recommends Avastin as a preferred therapy in combination with carboplatin and paclitaxel in appropriate patients for the first-line treatment of advanced non-squamous NSCLC, the leading cause of cancer deaths in the U.S.7
Avastin Safety First-Line Metastatic Colorectal Cancer In pivotal trials, the most serious adverse events associated with Avastin were GI perforation, wound healing complication, hemorrhage, non-GI fistula formation, arterial thromboembolic events, hypertensive crisis, reversible posterior leukoencephalopathy syndrome, neutropenia and infection, nephrotic syndrome, and congestive heart failure. The most common severe (grade 3-5) adverse events in Study E4599, occurring at a ≥2% higher incidence in Avastin-treated patients vs controls, were neutropenia, fatigue, hypertension, infection, and hemorrhage.
View full prescribing information, including Boxed WARNINGS. For more information on Avastin, visit http://www.avastin.com.
Avastin Development Program Based on data showing that VEGF may play a broad role in a range of cancers, a global development program for Avastin currently includes more than 450 clinical trials in more than 30 different tumor types, including early-stage cancers. Avastin is also being studied in combination with other targeted therapy agents in the absence of chemotherapy.
References
1 Genentech. "Avastin. Full Prescribing Information."
2 American Cancer Society. "Leading Sites of New Cancer Cases and Deaths - 2007 Estimates." Available at http://www.cancer.org/downloads/stt/CFF2007LeadingSites.pdf. Accessed May 7, 2007.
3 Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N. Vascular endothelial growth factor is a secreted antiogenic mitogen. Science. 1989;246:1306-1309.
4 Rosen LS. Clinical experience with angiogenesis signaling inhibitors: focus on vascular endothelial growth factor (VEGF) blockers. Cancer Control. 2002;9:36-44.
5 Kerbel R, Folkman J. Clinical translation of angiogenesis inhibitors. Nat Rev Cancer. 2002;2:727-739.
6 Jain RK. Normalizing tumor vasculature with antiangiogenic therapy: a new paradigm for combination therapy. Nat Med. 2001;7:987-989.
7 Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun M. Cancer statistics, 2007. CA Cancer J Clin. 2007;57:43-66.