• Oncology Clinical Trials
• Reproductive Cancers

• Oncology Clinical Trials
• Reproductive Cancers
• Oncology

Bevacizumab (BEV) is the first targeted agent that when added to standard chemotherapy improved overall survival (OS) in women with metastatic or relapsed cervical cancer. This finding from a randomized, open-label Phase 3 study represents the first instance in which a targeted therapy has significantly prolonged survival in this setting. Results were presented by Krishnansu S. Tewari, MD, University of California Irvine, Irvine, California, USA.

Acquired drug resistance to platinum-based therapies has rendered these treatments less effective for cervical cancer recurrence, leading to poor outcomes. Tumor neovascularization imparts an aggressive course in cervical cancer, prompting this investigation of an antiangiogenesis therapy targeting the vascular endothelial growth factor A (VEGF-A) in patients with relapsed or advanced disease.

The Paclitaxel and Cisplatin or Topotecan With or Without Bevacizumab in Treating Patients With Stage IVB, Recurrent, or Persistent Cervical Cancer study of the Gynecological Oncology Group [GOG 240; NCT00803062; Tewari KS et al. J Clin Oncol 2013 (suppl; abstr 3)] included 452 women with recurrent or metastatic cervical cancer who were randomized to 1 of 4 treatment arms using a 2×2 factorial design: 1) treatment with paclitaxel (PAC) 135 or 175 mg/m² intravenously (IV) plus cisplatin (CIS) 50 mg/m² IV; 2) PAC/CIS plus BEV 15 mg/kg IV; 3) PAC 175 mg/m² IV plus topotecan (TOPO) 0.75 mg/m² on Days 1 to 3; or 4) PAC/TOPO plus BEV 15 mg/kg IV. Patients were treated every 21 days until progression, unacceptable toxicity, or complete response. To be eligible, patients had to have measureable disease, a performance status of 0 to 1, and no prior chemotherapy for recurrent disease. The nonplatinum regimen selected was based on laboratory data indicating synergy between TOPO and microtubule-interfering agents and demonstrated activity in recurrent cervical cancer.

A preplanned interim analysis comparing the platinum doublet and the nonplatinum doublet on median OS showed no significant difference between the chemotherapy-alone groups (median OS, 15 months with PAC/CIS versus 12.5 months with PAC/TOPO; one-sided p=0.880).

Median progression-free survival was improved from a mean of 5.9 months with chemotherapy alone to 8.2 months with the addition of BEV. Similarly the response rate was significantly higher with BEV plus chemotherapy compared with chemotherapy alone (48% vs 36%; p=0.0078), with significantly more complete responses in patients treated with anti-VEGF therapy.

Median OS was 17.0 months in BEV-treated patients versus 13.3 months in the arms assigned to chemotherapy alone (HR, 0.71; p=0.0035). Median OS was superior with the addition of BEV to either chemotherapy regimen, although this difference achieved statistical significance when comparing BEV/CIS/PAC to CIS/PAC alone (17.5 vs 14.3 months, respectively; p=0.0348).

There were four fatal adverse events each with BEV and chemotherapy alone. No new side effects were identified with BEV. Gastrointestinal fistula grade ≥3, a recognized complication of BEV, occurred in 7 (3%) of BEV-treated patients and none of those on chemotherapy alone. Grade ≥2 hypertension was a complication in 54 patients (25%) of the BEV group and 4 (2%) of the group that received chemotherapy alone, but no patient withdrew from the study because of hypertension.

Health-related quality of life was measured by the Functional Assessment of Cancer Therapy-Cervical Cancer-Trial Outcome Index. The score on this index ranges from 0 to 116 points, with a clinically meaningful change being 4 to 5 points, said Dr. Tewari. Scores on this index were marginally lower, a maximum of 2.95 points and a mean of 1.2 points lower (p=0.3), in the BEV groups compared with the groups that received only chemotherapy, indicating no significant deterioration in quality of life.

BEV represents the first targeted agent that improves the outcome of metastatic or relapsed cervical cancer when added to an established chemotherapy regimen.

• © 2013 MD Conference Express®