Chicago, IL—Adding bevacizumab (Avastin) to standard chemotherapy improves overall survival (OS) in women with metastatic or relapsed cervical cancer, representing the first instance in which a targeted therapy has significantly prolonged OS in this patient population.
This phase 3 randomized clinical trial showed a near 4-month improvement in survival by adding bevacizumab to either paclitaxel (Taxol) plus cisplatin (Platinol) or to paclitaxel plus topotecan (Hycamtin), said Krishnansu S. Tewari, MD, Professor of Obstetrics and Gynecology, University of California, Irvine, at the 2013 American Society of Clinical Oncology annual meeting.
Few options currently exist for women with relapsed cervical cancer. Cisplatin plus paclitaxel is the standard of care, but it extends survival by ≤12 months. Acquired drug resistance to cisplatin plus paclitaxel or to platinum-based chemoradiation renders these treatments less effective for recurrence, leading to poor outcomes, said Dr Tewari.
Because angiogenesis appears to play an active role in cervical carcinogenesis and its progression, an antiangiogenesis therapy, such as bevacizumab, was a logical option to study in patients with relapsed or advanced disease, he said.
The National Cancer Institute–funded study included 452 women with recurrent or metastatic cervical cancer who were randomized to 1 of 4 arms—treatment with paclitaxel plus cisplatin, paclitaxel plus cisplatin plus bevacizumab, paclitaxel plus topotecan, or paclitaxel plus topotecan plus bevacizumab. Patients could not have received previous chemotherapy for a recurrence.
There was no significant difference in OS between the 2 chemotherapy arms. Progression-free survival was improved from a mean 5.9 months with chemotherapy alone to 8.2 months with the addition of bevacizumab. The response rate was significantly higher with bevacizumab plus chemotherapy compared with chemotherapy alone (48% vs 36%, respectively; P = .0078).
Most notable, median OS was 17.0 months in the arms that received bevacizumab versus 13.3 months for those that received chemotherapy without bevacizumab—a 29% reduction in the risk of death (P = .0035). The 3.7-month OS improvement “is clinically meaningful in a population of patients that doesn’t respond to chemotherapy very well,” said Dr Tewari.
There were 4 fatal adverse events each with bevacizumab and with chemotherapy alone. “No new side effects were identified with bevacizumab,” he emphasized. Gastrointestinal fistula occurred in 7 (3%) bevacizumab-treated patients and in none of the patients receiving chemotherapy alone. “This is a recognized complication of this drug,” Dr Tewari added.
Grade ≥2 hypertension was a complication in 54 (25%) of the patients in the bevacizumab group and in 4 (2%) of the group that received chemotherapy alone, but no patients withdrew from the study because of hypertension.
Health-related quality of life, as measured by the Functional Assessment of Cancer Therapy for cervical cancer index, was marginally worse, a maximum of 2.95 points, in the bevacizumab group versus the group that received only chemotherapy. (The score on this index ranges from 0 to 116 points, with a clinically meaningful change being 4 to 5 points.)
“I’m hoping that the data are strong enough to allow this drug to be approved for this indication, and I do believe ultimately that it will change practice,” said Dr Tewari. The finding may open the door to testing other antiangiogenesis drugs in the setting of advanced cervical cancer, he suggested.
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