Bevacizumab plus Chemotherapy to Treat Cervical Cancer

Chicago—Patients with recurrent and metastatic cervical cancer who received bevacizumab with their chemotherapy regimens had statistically significant improvement in overall survival compared with those taking chemotherapy alone, according to a phase 3, randomized trial. The median overall survival was 17.0 months in the bevacizumab group and 13.3 months in the chemotherapy alone group (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.54-0.94; P=.0035).

The 3.7 month overall survival advantage for patients receiving bevacizumab was “clinically meaningful,” according to Krishnansu Sujata Tewari, MD, the study’s lead author who presented the data during the plenary session at the ASCO meeting. The National Cancer Institute supported the study. Genentech, Inc., the drug’s manufacturer, provided bevacizumab in the trial.

Bevacizumab, which is administered via intravenous infusion, is the first molecularly targeted therapy to significantly prolong survival in a gynecologic cancer. The FDA has not approved the drug for women with metastatic or relapsed cervical cancer, but bevacizumab is approved to treat metastatic colorectal cancer, nonsquamous non–small-cell lung cancer, glioblastoma, and metastatic renal cell carcinoma.

Dr. Tewari said there are approximately 500,000 new cases of cervical cancer each year, and there are 250,000 deaths related to the disease each year. The disease is difficult to treat and is found early in life, with an average age at diagnosis of 47 years. Patients with cervical cancer also are often resistant to drug therapy. The standard of care for advanced cervical cancer is
50 mg/m² of cisplatin plus 135 mg/m² of paclitaxel, which extends survival by a median of ≤12 months. If patients do not respond to cisplatin plus paclitaxel, they die, according to Dr. Tewari.

This study included 452 women with primary, stage IVB, recurrent cervical cancer who had relapsed after previously receiving radiation and chemotherapy, but had not received chemotherapy for recurrence. They were recruited between April 2009 and January 2012 and randomized to receive cisplatin plus paclitaxel, topotecan plus paclitaxel, or either of those regimens plus bevacizumab. Of the patients, 225 received chemotherapy alone and 227 received chemotherapy plus bevacizumab. The groups were well balanced. The median age was approximately 47 years, and approximately 80% of patients were white. More than 70% of patients had received prior platinum-based chemotherapy with radiation.

The median progression-free survival was 5.9 months for the chemotherapy alone regimens and 8.2 months in the chemotherapy plus bevacizumab groups (HR, 0.67; 95% CI, 0.54-0.82; P=.0002). The response rates were 48% for patients receiving bevacizumab and 36% for patients only receiving chemotherapy (P=.00807).

In addition, the median overall survival was 14.3 months for patients taking cisplatin and paclitaxel and 17.5 months for patients receiving cisplatin, paclitaxel, and bevacizumab (HR, 0.68; 95% CI, 0.48-0.97; P=.0348). The response rates were 45% for patients taking cisplatin and paclitaxel and 50% for patients receiving cisplatin, paclitaxel, and bevacizumab (P=.5090).

The median overall survival was 12.7 months for patients taking topotecan and paclitaxel and 16.2 months for patients receiving topotecan, paclitaxel, and bevacizumab (HR, 0.74; 95% CI, 0.53-1.05; P=.0896). The response rates were 27% for patients taking topotecan and paclitaxel and 47% for patients receiving topotecan, paclitaxel, and bevacizumab (P=.0022).

The median number of treatment cycles was 6 for the chemotherapy alone groups and 7 for the chemotherapy plus bevacizumab groups. There were fatal adverse events in 4 patients in each group.

The side effects were similar between the groups, and none of the side effects associated with bevacizumab were new, according to Dr. Tewari. Although hypertension was more prevalent in patients receiving bevacizumab, none of those patients discontinued treatment, according to Dr. Tewari. He added that genitourinary and gastrointestinal fistulas of grade 3 or higher as well as thromboembolic events were more common in patients taking bevacizumab.