Avastin (Bevacizumab) Plus Chemotherapy Gets FDA Nod for Treatment of Advanced Cervical Cancer
First biologic/chemo combination approved for this indication
The FDA has approved Avastin (bevacizumab, Roche) in combination with paclitaxel and cisplatin or paclitaxel and topotecan for the treatment of women with persistent, recurrent or metastatic carcinoma of the cervix.
With this approval in advanced cervical cancer, Avastin is now approved in the U.S. to treat five distinct tumor types. The approval in advanced cervical cancer was based on the GOG-0240 study, an independent, National Cancer Institute-sponsored trial conducted by the Gynecologic Oncology Group.
The new study assessed the efficacy and safety profile of bevacizumab plus chemotherapy (paclitaxel and cisplatin or paclitaxel and topotecan) in 452 women with persistent, recurrent, or metastatic cervical cancer. The study met its primary endpoint of improving overall survival (OS), with a statistically significant 26% reduction in the risk of death for women who received bevacizumab plus chemotherapy compared with those who received chemotherapy alone (median OS: 16.8 months vs. 12.9 months, respectively; hazard ratio [HR] = 0.74; P = 0.0132).
Moreover, women who received bevacizumab plus chemotherapy had a significantly higher rate of tumor shrinkage (objective response rate) compared with chemotherapy alone (45% vs. 34%, respectively).
Hypertension of grade 2 or higher was significantly more common with bevacizumab- containing regimens compared with chemotherapy alone (29% vs. 6%, respectively), but no patients discontinued bevacizumab because of hypertension. Grade 3 or higher thrombosis was significantly increased with the bevacizumab-containing regimens (8.3% vs. 2.7%).
Gastrointestinal-vaginal fistulas occurred in 8.2% of patients receiving bevacizumab-containing regimens compared with 0.9% of those treated with chemotherapy alone; all of the affected patients had a history of prior pelvic radiation. Patients who develop these fistulas may require additional surgery. Moreover, 1.8% of bevacizumab-treated patients and 1.4% of control patients had non-gastrointestinal fistulas in the vaginal, vesical, or female genital tract.
Gastrointestinal perforations also occurred in 3.2% of bevacizumab-treated patients, all of whom had a history of prior pelvic radiation. There was no increase in treatment-related deaths in the bevacizumab-plus-chemotherapy arm compared with the chemotherapy-alone arm.
An independent blood supply is critical for a tumor to grow beyond a certain size (2 mm) and to metastasize to other parts of the body. Tumors develop their own blood supply (angiogenesis) by releasing vascular endothelial growth factor (VEGF) — a key driver of tumor growth. Bevacizumab is an antibody that targets and inhibits VEGF. This inhibition by bevacizumab allows the drug to be combined with a broad range of chemotherapies and other anti-cancer treatments with little additional impact on the side effects of these therapies.
Source: Roche; August 15, 2014.