Defining Optimal Therapy for Metastatic and Recurrent Cervical Cancer
Name of the Trial
Phase III Randomized Study of Paclitaxel in Combination with Cisplatin or Topotecan Hydrochloride with Versus without Bevacizumab in Patients with Stage IVB, Recurrent, or Persistent Carcinoma of the Cervix (GOG-0240). See the protocol summary.
Dr. Krishnansu Tewari, Gynecologic Oncology Group
Why This Trial Is Important
Treatment options are limited for women with metastatic or recurrent cervical cancer. Currently, treatment of these women often includes chemotherapy with the drug cisplatin. Unfortunately, only up to one third of patients with metastatic and recurrent disease will respond to cisplatin-based chemotherapy, and these responses are short-lived, on the order of months. Additionally, because cisplatin-based chemotherapy (in combination with radiation therapy) is also used to treat patients with earlier-stage disease, recurrent cervical cancer may be resistant to additional treatment with platinum drugs. Therefore, doctors are trying to find alternative, non-platinum combinations for advanced disease that are able to shrink tumors and help patients live longer. Previous clinical trials have offered some promising leads, indicating that patients may benefit from treatment with the drugs paclitaxel and topotecan, as well as biological agents that target tumor angiogenesis.
A recent phase III trial of four cisplatin-based chemotherapy combinations in patients with advanced cervical cancer showed a trend toward better survival when cisplatin was combined with paclitaxel. The trial was stopped early, however, because none of the regimens appeared likely to provide a statistically meaningful benefit over the others, reinforcing the need for a non-platinum-based option. Topotecan combined with cisplatin has also demonstrated benefit in patients with advanced disease, but researchers suspect much of this benefit may be due to the effects of topotecan alone. These observations provide a rationale for pairing paclitaxel and topotecan, and a small pilot study demonstrated that the combination is safe and clinically active.
Antiangiogenesis therapy using the biological agent bevacizumab is also being investigated in women with advanced cervical cancer. Results of a phase II trial of bevacizumab alone in women with persistent (refractory) or recurrent disease showed the drug to be well tolerated and active.
In this phase III trial, women with metastatic, recurrent, or persistent cervical cancer that cannot be treated with surgery and/or radiation therapy will be randomly assigned to one of four treatment groups: paclitaxel plus cisplatin, paclitaxel plus topotecan, or either of these combinations with the addition of bevacizumab. Doctors will compare overall survival and the frequency and severity of side effects in patients treated with these regimens.
"Women with such advanced cervical cancer unfortunately have very few treatment options," said Dr. Tewari. "So, it's critical for them to explore clinical trials. This is the first randomized phase III study of a targeted agent in metastatic or recurrent cervical cancer, and it is the only U.S. phase III trial exploring the use of non-platinum combination chemotherapy in this patient population."
For More Information
On February 7, 2013, NCI and the Gynecologic Oncology Group announced interim results of the study, which showed the addition of bevacizumab to standard chemotherapy with cisplatin and paclitaxel led to a significant improvement in overall survival.