Bevacizumab Improves OS in Recurrent, Platinum-Sensitive Ovarian Cancer

Robert Coleman, MD

Adding bevacizumab (Avastin) to standard platinum-based chemotherapy was associated with a clinically significant improvement in median overall survival (OS) in women with recurrent ovarian cancer, according to results from the phase III GOG-0123 trial published online in The Lancet Oncology.¹

Median OS was 42.2 months (95% CI, 37.7-46.2) for the group assigned to bevacizumab with paclitaxel and carboplatin compared with 37.3 months (95% CI, 32.6-39.7) for the group receiving paclitaxel and carboplatin alone (HR, 0.83; 95% CI, 0.68-1.05; P = .056).

“We show in this phase III trial that bevacizumab added to paclitaxel and carboplatin might favorably affect overall survival in women with platinum-sensitive recurrent ovarian cancer,” wrote the authors, led by Robert L. Coleman, MD, Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center. “We believe that the improvement in median overall survival of about 5 months in the bevacizumab group is clinically meaningful for both patients and clinicians.

“Additionally, [bevacizumab] significantly improves progression-free survival and objective response. We did not observe any new safety signals nor toxicity that differentially increased treatment discontinuation.”

Median progression-free survival was 13.8 months in the bevacizumab group versus 10.4 months in the chemotherapy-alone group (HR, 0.63; 95% CI, 0.53-0.74; P <.0001).

Researchers performed an exploratory posthoc analysis of investigator-assessed objective response for 509 (76%) patients with measurable disease who could be assessed with serial imaging. Bevacizumab was associated with a much greater objective response rate (ORR) compared with chemotherapy (78% vs 59%). Furthermore, a higher number of patients in the bevacizumab group achieved a complete response (32% vs 18%).

Researchers at 67 treatment centers in the United States, Japan, and South Korea recruited women with recurrent measurable or evaluable epithelial ovarian, primary peritoneal, or fallopian tube cancer from December 2010 to August 2011. Eligible patients had achieved clinical complete response to primary platinum-based chemotherapy and had been disease-free for at least 6 months following their last infused cycle of platinum.

Patients in the control group (n = 337) were assigned to 175 mg/m² IV paclitaxel followed by carboplatin (AUC = 5). Patients in the experimental group (n = 377) also received 15 mg/kg IV bevacizumab (15 mg/kg bodyweight) sequenced between paclitaxel and carboplatin on the day of infusion.

Researchers replaced paclitaxel with 75 mg/m² IV docetaxel in patients who developed dose-limiting peripheral neuropathy or hypersensitivity.

In the maintenance phase, the same dose of bevacizumab was administered every 3 weeks until disease progression or unacceptably toxicity. Chemotherapy in both groups was planned for six 3-week cycles, but patients who demonstrated partial or complete response could undergo 2 additional cycles.

About 20% of patients received intraperitoneal chemotherapy as first-line therapy before going on-trial, while 89 (13%) had maintenance therapy following initial chemotherapy. Sixty-seven patients (10%) received prior bevacizumab. A cohort of patients (n = 107) equally represented in both study groups were considered surgical candidates and underwent randomization for a secondary cytoreduction cohort.

Bevacizumab was delayed until cycle 2 in patients who had surgery to avoid wound healing complications.

Patients in the bevacizumab group were more likely to experience at least one grade 3 or higher adverse event (AE). In the chemotherapy group, 282 of 327 patients (86%) experienced at least one grade 3 or higher AE compared with 317 of 330 patients (96%) in the bevacizumab group. The most frequently reported grade 3 or higher treatment-related AEs reported in the bevacizumab group were hypertension (12% vs 1% in the chemotherapy group), fatigue (8% vs 2%), and proteinuria (8% vs 0).

Writing in an accompanying editorial,² Phillip Harter, MD, PhD, with Kliniken-Essen-Mitte in Essen, Germany, said that these results show that “clinicians now have a further option for the treatment of patients with platinum-sensitive recurrent ovarian cancer,” but that the physicians must take care to determine which patients should receive platinum-based chemotherapy and which should receive a PARP inhibitor.

“Is the patient symptomatic and in need of an urgent response or at risk for progressive disease under platinum retreatment?” he wrote. “This scenario would favor the addition of bevacizumab, which shows improved objective response compared with chemotherapy alone. Conversely, a positive BRCA status could help to select patients in whom treatment with a PARP inhibitor is the best option.”

References

1. Coleman RL, Brady MF, Herzog TJ, et al. Bevacizumab and paclitaxel—carboplatin chemotherapy and secondary cytoreduction in recurrent, platinum-sensitive ovarian cancer (NRG Oncology/Gynecologic Oncology Group study GOG-0213): a multicentre, open-label, randomised, phase 3 trial [published online April 21, 2017]. Lancet Oncol. doi: 10.1016/ S1470-2045(17)30279-6.
2. Harter P. A new standard of care or just another option for patients with relapsed ovarian cancer? [published online April 21, 2017]. Lancet Oncol. doi:10.1016/S1470-2045(17)30253-X

Researchers later noticed incorrect treatment-free interval stratification data for 45 patients, 7% of the total population equally balanced between both treatment groups. Sensitivity analysis of OS based on audited treatment-free interval stratification data resulted in an adjusted HR of 0.82 (95% CI, 0.68-0.996; P = .045).