NEW YORK (Reuters Health) - Carboplatin-pegylated liposomal doxorubicin-bevacizumab is the new standard of care for women with recurrent ovarian cancer sensitive to treatment with platinum-based and antiangiogenic treatment, researchers say.
“This is the first phase-3 study comparing two bevacizumab-containing regimens in recurrent ovarian cancer,” Dr. Jacobus Pfisterer of the Gynecologic Oncology Center in Kiel, Germany, told Reuters Health by email. “The experimental arm did better than the current standard of care with respect to progression-free survival and overall survival, with no new toxicities.”
German national guidelines were changed to incorporate the study results, he noted. “The experimental arm is the new standard of care. The next step is a phase-3 study adding immunotherapy” to this regimen, he said.
The multicenter open-label trial involved 682 patients (median age, about 63) randomized to receive carboplatin-pegylated liposomal doxorubicin-bevacizumab (experimental group) or carboplatin-gemcitabine-bevacizumab (standard group).
The experimental group received six cycles of bevacizumab (10 mg/kg, days 1 and 15) plus carboplatin (area under the concentration curve 5, day 1) plus pegylated liposomal doxorubicin (30 mg/m2, day 1) every four weeks.
The standard group received six cycles of bevacizumab (15 mg/kg, day 1) plus carboplatin (AUC 4, day 1) plus gemcitabine (1000 mg/m2, days 1 and 8) every three weeks.
Both regimens were followed by maintenance bevacizumab (15 mg/kg every three weeks until disease progression or unacceptable toxicity).
As reported in The Lancet Oncology, median progression-free survival was 13.3 months in the experimental group versus 11.6 months in the standard group (hazard ratio, 0.81).
Median overall survival, a secondary endpoint, was 31.9 months in the experimental group versus 27.8 months in the standard group (HR 0.81).
Eighty-four patients (11%, experimental group vs.14%, standard) received post-progression bevacizumab for a median duration of 20.5 days (both groups).
Almost all patients had at least one adverse event during the study (98% vs. 97%).
The most common grade 3 or 4 adverse events were hypertension (27%, experimental vs. 20%, standard) and neutropenia (12% vs. 22%). Serious adverse events occurred in 10% of experimental group patients and 9% of those in the standard group.
One treatment-related death occurred in the experimental group (large intestine perforation) and two in the standard group (one case each of osmotic demyelination syndrome and intracranial hemorrhage).
The authors conclude, “Carboplatin-pegylated liposomal doxorubicin-bevacizumab is a new standard treatment option for platinum-eligible recurrent ovarian cancer.”
Dr. Richard Penson of Massachusetts General Hospital in Boston, author of a related editorial, commented by email to Reuters Health, “The unexpected result was that carboplatin, pegylated liposomal doxorubicin, and bevacizumab (CD-BEV) improved overall survival by four months, with significant improvements in quality of life, meeting all the criteria for a new standard of care.”
“Establishing ‘optimal’ chemotherapy is a complicated trade-off between being toxic to the cancer and kind to the patient,” he said. “CD-BEV may have that balance just right, though guidelines tend to reflect clinicians’ wish to maximize the number of options, rather than ranking them.”
“The greatest benefit to the regimen is that it potentially gets the greatest good for the greatest number, by delivering the best chance of remission that can consolidated by the use of a PARP inhibitor, and it is this ‘switch maintenance’ that offers the hope for the most durable control of a dreadful disease,” he concluded.
The study was funded by F Hoffmann-LaRoche. Dr. Pfisterer and numerous coauthors have received fees from the company.