The FDA has assigned a priority review designation to bevacizumab (Avastin) plus chemotherapy as a treatment for patients with persistent, recurrent, or metastatic cervical cancer.
Cytological specimen showing cervical cancer specifically squamous cell carcinoma in the cervix. Tissue is stained with pap stain and magnified x200.
SOURCE: The Web site of the National Cancer Institute (http://www.cancer.gov).
The FDA has assigned a priority review designation to bevacizumab (Avastin) plus chemotherapy as a treatment for patients with persistent, recurrent, or metastatic cervical cancer. As part of this program, the agency plans to take action on the drug's application within 6 months instead of the standard 10 months under regular review. Based on the time of submission, Genentech, the company that markets the drug, announced an FDA action date of October 24, 2014.
Priority review was based on results from the phase III GOG 240 study, which demonstrated that treatment with bevacizumab combined with chemotherapy improved overall survival (OS) by 29% compared with chemotherapy alone in patients with advanced cervical cancer. Results from the study were initially presented at the 2013 ASCO Annual Meeting. In February 2014, the results were also published in theNew England Journal of Medicine.1
“The findings in this clinical trial are important because they are likely to change clinical practice and provide an opportunity to improve outcome in patients with recurrent cervical cancer who have previously had very limited treatment options,” lead study investigator Krishnansu S. Tewari, MD, a professor of obstetrics and gynecology at the University of California Irvine, said when the findings were presented.
In the study, 452 patients were randomized to receive 1 of 2 standard chemotherapy regimens with or without bevacizumab. The first chemotherapy regimen consisted of cisplatin at 50 mg/m2plus paclitaxel at 135 or 175 mg/m2. The second regimen contained topotecan at 0.75 mg/m2on days 1 to 3 plus paclitaxel at 175 mg/m2on day 1 of a 21-day cycle. Bevacizumab was administered at 15 mg/kg. The primary endpoint was OS, with a reduction of 30% in the hazard ratio considered clinically important.
The addition of bevacizumab to chemotherapy was associated with increased OS. For the two chemotherapy regimens with the addition of bevacizumab, the median OS was 17.0 months compared with 13.3 months for chemotherapy alone (HR = 0.71; 98% CI, 0.54-0.95;P= .004). The median progression-free survival was 8.2 months in the combination arms, versus 5.9 months without bevacizumab (HR = 0.67; 95% CI, 0.54-0.82), and the objective response rate (ORR) was 48% compared with 36% (P= .008), for the combination and chemotherapy alone, respectively.
For patients receiving paclitaxel/cisplatin plus bevacizumab versus those in the paclitaxel/cisplatinalone arm, the hazard ratio for OS was 0.68, and ORR was 50% versus 45%, respectively (P= .51). In the topotecan/paclitaxel arms, the hazard ratio for OS when bevacizumab was added was 0.74, with an ORR of 47% with the combination versus 27% with chemotherapy alone (P= .002). The comparison of the two chemotherapy arms did not demonstrate OS superiority for topotecan plus paclitaxel over cisplatin plus paclitaxel (HR = 1.20).
Consistent with the mechanism of action, hypertension of grade 2 or higher was significantly more common with bevacizumab (25% vs 2%,P<.001). However, hypertension did not lead to the discontinuation of therapy for any patients. Grade 3/4 gastrointestinal or genitourinary fistulas (6% vs 0%) and thromboembolic events (8% vs 1%) were significantly increased with the addition of bevacizumab. Fatal adverse events were the same in both treatment groups.
“This regulatory application for Avastin is important because chemotherapy is the only approved treatment for women with metastatic, recurrent, or persistent cervical cancer,” Sandra Horning, MD, chief medical officer and head of Global Product Development at Roche, the parent group of Genentech. “Treatment with Avastin plus chemotherapy may help women with these conditions live longer than chemotherapy alone, and we look forward to working with the FDA on potentially making this medicine available to patients.”
Bevacizumab is approved in various settings for patients with metastatic colorectal cancer, metastatic non-squamous non-small cell lung cancer, recurrent glioblastoma, and metastatic renal cell carcinoma. Additionally, the treatment has demonstrated promise in patients with ovarian cancer.