The FDA yesterday approved a fifth oncology indication for the Roche/Genentech drug Avastin (bevacizumab), allowing its use in women with persistent, recurrent or metastatic cervical cancer in combination with paclitaxel and cisplatin or paclitaxel and topotecan.
Avastin becomes the first treatment to be approved besides chemo for those forms of carcinoma of the cervix—and the first drug approved by the FDA for any form of cervical cancer since 2006, when topotecan was allowed as a treatment in combination with cisplatin.
The new indication was approved in less than four months under FDA’s priority review program.
FDA based its approval on the Phase III GOG-0240 trial, a National Cancer Institute (NCI)-sponsored study of the Gynecologic Oncology Group (GOG) that assessed the efficacy and safety profile of Avastin plus chemotherapy (paclitaxel and cisplatin or paclitaxel and topotecan) in women with persistent, recurrent or metastatic cervical cancer.
Study data from 452 women showed that Avastin met its primary endpoint of improving overall survival (OS) with a statistically significant 26% reduction in the risk of death for women who received Avastin plus chemotherapy, compared to women who received chemotherapy alone. The median OS for Avastin-plus-chemo patients was 16.8 months, compared with 12.9 months for chemo alone.
GOG-0240 also showed that women who received Avastin plus chemotherapy had a significantly higher rate of tumor shrinkage (45%) compared to chemotherapy alone (34%).
“With this approval, women with advanced cervical cancer now have the option of Avastin plus chemotherapy to help them live longer than with chemotherapy alone,” Sandra Horning, M.D., CMO and head of global product development at Roche, said in a statement.
While there was no increase in treatment-related deaths in the Avastin-plus-chemotherapy arm compared with the chemotherapy arm, hypertension of Grade 2 or higher was significantly more common with Avastin-containing regimens (29% vs. 6%). No patients discontinued Avastin because of hypertension, however.
The proportion of patients with thrombosis of Grade 3 or higher was significantly increased in the Avastin arm (8.3% vs. 2.7%). Gastrointestinal-vaginal fistulas occurred in 8.2% of Avastin patients vs. 0.9% of chemo-alone patients, all of whom had a history of prior pelvic radiation. Another 1.8% of Avastin-treated patients had non-gastrointestinal fistulas in the vaginal, vesical, or female genital tract, compared with 1.4% of chemo-alone patients.
Avastin’s other approved U.S. indications include treatment of colorectal cancer, non-small cell lung cancer, kidney cancer, and progressive glioblastoma following prior therapy. In Europe, Avastin is additionally indicated for advanced stages of breast cancer and ovarian cancer.
The drug was also approved in the U.S. in 2008 for women with HER2-negative metastatic breast cancer in combination with paclitaxel—but FDA Commissioner Margaret A. Hamburg, M.D., withdrew the approval in 2011 over objections from Roche/Genentech and numerous patients. At the time, the agency cited the failure of several clinical studies combining Avastin with various chemo drugs to replicate or surpass the duration of progression-free survival seen in the study that was the basis for FDA’s approval.
The FDA’s decision marks the second new indication for which Avastin has received regulatory approval this month. On August 5, the European Commission allowed the drug to be used for a form of ovarian cancer.