• Reproductive Cancers
• Oncology Clinical Trials

In patients with ovarian cancer, progression-free survival (PFS) and overall response rate (ORR) are significantly improved with the addition of bevacizumab to chemotherapy in front-line [Burger RA et al. N Engl J Med 2011] and platinum-sensitive recurrent [Aghajanian C et al. J Clin Oncol 2012] settings, and as shown in the Phase 3 AURELIA: A Study of Avastin (Bevacizumab) Added to Chemotherapy in Patients with Platinum-Resistant Ovarian Cancer [AURELIA; NCT00976911] trial [Pujade-Lauraine E et al. J Clin Oncol 2012].

Andrés Poveda, MD, Fundación Instituto Valenciano de Oncología (IVO), Valencia, Spain, presented the results from a subanalysis of AURELIA that showed that the benefits of bevacizumab as add-on therapy are observed regardless of the choice of chemotherapy.

AURELIA, the first trial to compare bevacizumab plus chemotherapy versus chemotherapy alone in platinum-resistant ovarian cancer patients (epithelial ovarian, fallopian tube, or primary peritoneal cancer), was a multicenter, open-label, randomized, 2-arm trial. Patients with platinum-resistant ovarian cancer that had progressed <6 months after 4 cycles of platinum-based therapy were randomly assigned in 1:1 ratio to either chemotherapy alone or chemotherapy plus bevacizumab (15 mg/kg every 3 weeks) and treated until disease progression, unacceptable toxicity, or withdrawal of consent. Chemotherapy regimen was chosen by the investigator prior to randomization and included standard regimens of paclitaxel, topotecan, or pegylated liposomal doxorubicin (PLD). Stratification factors were the chemotherapy selected, prior antiangiogenic therapy, and treatment-free interval (<3 vs 3 to 6 months from previous platinum to subsequent progressive disease).

The primary objective was to compare PFS with chemotherapy alone versus chemotherapy plus bevacizumab according to Response Evaluation Criteria in Solid Tumors (RECIST v1.0) guidelines. Secondary objectives included ORR, overall survival, quality of life, safety, and tolerability.

Subjects were median ∼60 years of age. Approximately 25% had a progression-free interval of less than 3 months. More patients in the paclitaxel cohort had received 2 prior chemotherapy regimens compared with the PLD and topotecan cohorts.

In the patients with platinum-resistant ovarian cancer, the addition of bevacizumab to single-agent chemotherapy was associated with improvements in median PFS (Table 1) and ORR across all chemotherapy cohorts.

The bevacizumab plus chemotherapy arm was associated with a higher incidence of grade ≥2 peripheral sensory neuropathy and grade ≥3 neutropenia in the paclitaxel cohort, and grade ≥2 hand-foot syndrome and grade ≥3 hypertension in the PLD cohort. Incidence rates of grade ≥3 neutropenia and leucopenia were higher in the chemotherapy-alone arm.

The effects of bevacizumab on PFS within the individual chemotherapy cohorts were consistent with the results in the overall population. Increased chemotherapy exposure associated with prolonged PFS accounted for some increase in cumulative chemotherapy toxicity. However, overall, there was no indication that bevacizumab exacerbates chemotherapy-related adverse events. The authors concluded that bevacizumab plus chemotherapy should be considered a new standard option in platinum-resistant ovarian cancer.

• © 2012 MD Conference Express®