FDA approves Avastin to treat patients with aggressive and late-stage cervical cancer

August 14, 2014

The U.S. Food and Drug Administration today approved a new use for Avastin (bevacizumab) to treat patients with persistent, recurrent or late-stage (metastatic) cervical cancer.

Cervical cancer grows in the tissues of the lower part of the uterus known as the cervix. It commonly occurs when human papillomaviruses (HPV), a virus that spreads through sexual contact, cause cells to become cancerous. Although there are two licensed vaccines available to prevent many types of HPV that can cause cervical cancer, the National Cancer Institute estimates that 12,360 American women will be diagnosed with cervical cancer and 4,020 will die from the disease in 2014.

Avastin works by interfering with the blood vessels that fuel the development of cancerous cells. The new indication for cervical cancer is approved for use in combination with chemotherapy drugs paclitaxel and cisplatin or in combination with paclitaxel and topotecan.

“Avastin is the first drug approved for patients with late-stage cervical cancer since the 2006 approval of topotecan with cisplatin,” said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “It is also the first biologic agent approved for patients with late-stage cervical cancer and was approved in less than four months under the FDA’s priority review program, demonstrating the agency’s commitment to making promising therapies available to patients faster.”

The FDA reviewed Avastin for treatment of patients with cervical cancer under its priority review program because the drug demonstrated the potential to be a significant improvement in safety or effectiveness over available therapy in the treatment of a serious condition. Priority review provides an expedited review of a drug’s application.

The safety and effectiveness of Avastin for treatment of patients with cervical cancer was evaluated in a clinical study involving 452 participants with persistent, recurrent, or late-stage disease. Participants were randomly assigned to receive paclitaxel and cisplatin with or without Avastin or paclitaxel and topotecan with or without Avastin. Results showed an increase in overall survival to 16.8 months in participants who received chemotherapy in combination with Avastin as compared to 12.9 months for those receiving chemotherapy alone.

The most common side effects associated with use of Avastin in patients with cervical cancer include fatigue, decreased appetite, high blood pressure (hypertension), increased glucose in the blood (hyperglycemia), decreased magnesium in the blood (hypomagnesemia), urinary tract infection, headache and decreased weight. Perforations of the gastrointestinal tract and abnormal openings between the gastrointestinal tract and vagina (enterovaginal fistula) also were observed in Avastin-treated patients.

Avastin is marketed by South San Francisco, California-based Genentech, a member of the Roche Group.

A recombinant humanized monoclonal IgG1 antibody that binds to and inhibits the biologic activity of human vascular endothelial growth factor (VEGF). Bevacizumab contains human framework regions and the complementarity-determining regions of a murine antibody that binds to VEGF. Bevacizumab is produced in a Chinese Hamster Ovary mammalian cell expression system in a nutrient medium containing the antibiotic gentamicin and has a molecular weight of approximately 149 kilodaltons.

sequence

>"Bevacizumab light chain"
DIQMTQSPSSLSASVGDRVTITCSASQDISNYLNWYQQKPGKAPKVLIYFTSSLHSGVPS
RFSGSGSGTDFTLTISSLQPEDFATYYCQQYSTVPWTFGQGTKVEIKRTVAAPSVFIFPP
SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

>"Bevacizumab heavy chain"
EVQLVESGGGLVQPGGSLRLSCAASGYTFTNYGMNWVRQAPGKGLEWVGWINTYTGEPTY
AADFKRRFTFSLDTSKSTAYLQMNSLRAEDTAVYYCAKYPHYYGSSHWYFDVWGQGTLVT
VSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVL
QSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEL
LGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREE
QYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPS
REEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK
SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

Bevacizumab 

Monoclonal antibody
Type	Whole antibody
Source	Humanized (from mouse)
Target	VEGF-A
Clinical data
Trade names	Avastin
AHFS/Drugs.com	monograph
Licence data	EMA:Link, US FDA:link
Pregnancy cat.	C (US)
Legal status	℞ Prescription only
Routes	Intravenous
Pharmacokinetic data
Bioavailability	100% (IV only)
Half-life	20 days (range: 11–50 days)
Identifiers
CAS number	216974-75-3
ATC code	L01XC07
DrugBank	DB00112
UNII	2S9ZZM9Q9V
KEGG	D06409
ChEMBL	CHEMBL1201583
Chemical data
Formula	C6638H10160N1720O2108S44
Mol. mass	approx. 149 kDa