Richard Pazdur, MD
The FDA has approved bevacizumab (Avastin) in combination with paclitaxel plus cisplatin or topotecan as a treatment for patients with persistent, recurrent, or metastatic cervical cancer, based on the extension of overall survival (OS) in the phase III GOG 240 study.
In the phase III study, bevacizumab combined with chemotherapy improved OS by 26% compared with chemotherapy alone in patients with advanced cervical cancer. Additionally, the objective response rate (ORR) was superior with the addition of bevacizumab (45% vs 34%). The approval arrives approximately 2 months earlier than estimated under the FDA's priority review program and marks the first for a biologic agent for patients with cervical cancer.
“Avastin is the first drug approved for patients with late-stage cervical cancer since the 2006 approval of topotecan with cisplatin,” Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in a press release. “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.”
In the study, 452 patients were randomized in a 1:1:1:1 ratio to receive 1 of 2 standard chemotherapy regimens with or without bevacizumab. The first chemotherapy regimen consisted of cisplatin at 50 mg/m2
plus paclitaxel at 135 or 175 mg/m2
. The second regimen contained topotecan at 0.75 mg/m2
on days 1 to 3 plus paclitaxel at 175 mg/m2
on day 1 of a 21-day cycle. Bevacizumab was administered at 15 mg/kg every 3 weeks.
Overall, 78% of patients were Caucasian and 80% had received prior radiation therapy, with 74% of patients receiving concurrent chemoradiotherapy. The primary endpoint was OS, with a secondary endpoint focused on ORR.
According to the updated prescribing information, the median OS was 16.8 months with bevacizumab compared with 12.9 months for chemotherapy alone (HR = 0.74; 98% CI, 0.58-0.94; P
= .0132). The ORR with chemotherapy plus bevacizumab was 45% (95% CI, 0.39-0.52) compared with 34% (95% CI, 0.28-0.40) with chemotherapy alone.
The hazard ratio for OS with cisplatin, paclitaxel, and bevacizumab compared with cisplatin and paclitaxel alone was 0.72 (95% CI, 0.51-1.02). For topotecan, paclitaxel, bevacizumab versus chemotherapy alone, the hazard ratio was 0.76 (95% CI, 0.55-1.06). For patients treated with topotecan plus paclitaxel with or without bevacizumab, the median OS was 13.3 months compared with 15.5 months for patients treated with cisplatin and paclitaxel with or without bevacizumab (HR = 1.15; 95% CI, 0.91-1.46; P
Grade 2 or higher hypertension was significantly more common with bevacizumab (29% vs 6%). However, hypertension did not lead to the discontinuation of therapy for any patients. The most common grade 3/4 adverse events with bevacizumab (n = 218) versus chemotherapy alone (n = 222) were abdominal pain (11.9% vs 9.9%), diarrhea (5.5% vs. 2.7%), anal fistula (3.7% vs 0%), and proctalgia (2.8% vs 0%). Other serious adverse events that were more common in the bevacizumab arm compared with chemotherapy were thrombosis (8.3% vs 2.7%), gastrointestinal-vaginal fistulas (8.2% vs 0.9%), and non-gastrointestinal fistulas (1.8% vs 1.4%).
“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, MD, chief medical officer and head of Global Product Development, said in a statement. “Cervical cancer is most commonly diagnosed in women between the ages of 35 and 44, and until today, chemotherapy was the only approved treatment option for women whose cancer recurred, persisted or spread.”
A supplemental New Drug Application (sNDA) is currently pending for bevacizumab in combination with chemotherapy as a treatment for patients with recurrent platinum-resistant ovarian cancer. In July, Genentech announced that the FDA had granted a priority review to this sNDA with a decision deadline set for November 19, 2014.
Bevacizumab was first approved as a treatment for patients with cancer in 2004. It has since been approved across various settings as a treatment for patients with metastatic colorectal cancer, metastatic non-squamous non-small cell lung cancer, recurrent glioblastoma, and metastatic renal cell carcinoma.