For patients with recurrent ovarian cancer who receive platinum-based retreatment, the more suitable partner for bevacizumab (Avastin) may be carboplatin plus pegylated liposomal doxorubicin, rather than carboplatin and gemcitabine, according to the results of a phase III ENGOT/GCIG Intergroup Study—AGO OVAR 2.21—the first to compare two bevacizumab-containing regimens.¹

Jacobus Pfisterer, MD

As Jacobus Pfisterer, MD, Director of the Gynecologic Oncology Center in Kiel, Germany, reported at the European Society for Medical Oncology (ESMO) 2018 Congress, “The study met its primary objective, with carboplatin/pegylated liposomal doxorubicin/bevacizumab [CD-BEV] resulting in superior progression-free survival compared with carboplatin/gemcitabine/bevacizumab [CG-BEV].”

“CD-BEV also improved efficacy in the subgroup of patients with previous antiangiogenic treatment, global quality of life was slightly superior with CD-BEV, and CD-BEV was associated with fewer serious adverse events,” he added.

Trial Rationale

In patients with recurrent ovarian cancer suitable for retreatment with a platinum agent, standard therapy includes CG-BEV and carboplatin/pegylated liposomal doxorubicin alone. CG-BEV significantly increases progression-free survival over carboplatin/gemcitabine alone, whereas carboplatin/pegylated liposomal doxorubicin has one of the best therapeutic indices for recurrent platinum-sensitive ovarian cancer, he pointed out. “The aim of this trial was to evaluate whether carboplatin/pegylated liposomal doxorubicin is superior to carboplatin/gemcitabine when given in combination with bevacizumab,” he said.

Dr. Pfisterer noted that at the time of the study design, poly (ADP-ribose) polymerase (PARP) inhibitors were not the standard of care, and the study did not obtain information about BRCA-mutation status.

Study Details

AGO OVAR 2.21 included 682 patients with recurrent ovarian cancer (ovarian, fallopian tube, or primary peritoneal carcinoma) suitable for platinum-based therapy. Patients had recurred at least 6 months after first-line platinum-based chemotherapy, with more than two-thirds experiencing a platinum-free interval of at least 12 months. About 50% had prior antiangiogenic treatment, mostly with bevacizumab.

Patients were randomly assigned to receive bevacizumab at 15 mg/kg every 3 weeks until progressive disease or toxicity and either gemcitabine at 1,000 mg/m² on days 1 and 8 plus carboplatin AUC 4 on day 1 (the standard arm) or pegylated liposomal doxorubicin at 30 mg/m² on day 1 plus carboplatin AUC 5 on day 1 (the experimental arm) for 6 cycles every 3 weeks. The primary endpoint was investigator-assessed progression-free survival.

CD-BEV Superior to CG-BEV

The median progression-free survival was 11.7 months with CG-BEV and 13.3 months with CD-BEV (hazard ratio [HR] = 0.807; P = .0128). Biologic (CA-125) progression-free survival was 10.0 and 11.5 months, respectively (HR = 0.758; P = .0010).

CD-BEV was superior in all subgroups. Patients with previous antiangiogenic treatment experienced a reduction in disease progression of 27% (P < .05), Dr. Pfisterer reported.

The median overall survival was 28.2 months with CG-BEV vs 33.5 months with CD-BEV (HR = 0.833; P = .0787). Quality of life as assessed by the European Organisation for the Research and Treatment of Cancer Quality-of-Life Questionnaire and the Disease-Specific Questionnaire Module instruments favored CD-BEV as well; however, the differences were statistically significant only at the two earliest time points.

Serious adverse events occurred in 8.5% of the CG-BEV arm and 9.9% of the CD-BEV arm. Grade 3 to 5 adverse events of special interest occurred in 45.3% and 44.0%, respectively. Neutropenia grade ≥ 3 was observed in 22.2% of the CG-BEV arm and in 12.0% of the CD-BEV arm. Grade ≥ 3 hypertension, however, occurred in 20.7% and 27.7%, respectively. Dr. Pfisterer acknowledged that single-agent liposomal doxorubicin can produce skin toxicity but said the addition of bevacizumab did not increase its occurrence.

“CD-BEV is a new treatment option for patients with recurrent ovarian cancer suitable for platinum-based retreatment, even after previous antiangiogenic treatment,” Dr. Pfisterer concluded. ■

DISCLOSURES: The study was funded by F. Hoffmann-La Roche. Dr. Pfisterer is a consultant/advisor with Roche, Amgen, AstraZeneca, Coherus Bioscience, DeciBio Consulting, F. Hoffmann-La Roche, PharmaMar, Shield Therapeutics, Simon-Kucher & Partners, Taylor Wessing LLP, and Tesaro.

REFERENCE

1. Pfisterer J, Dean AP, Baumann K, et al: Carboplatin/pegylated liposomal doxorubicin/bevacizumab (CD-BEV) vs. carboplatin/gemcitabine/bevacizumab (CG-BEV) in patients with recurrent ovarian cancer. 2018 ESMO Congress. Abstract 933O. Presented October 19, 2018.