CHICAGO – Adding the antiangiogenic agent bevacizumab to platinum-based chemotherapy halves the risk of progression in women with recurrent ovarian, peritoneal, or fallopian tube cancer, new data show.
In OCEANS, a randomized phase III trial, patients given bevacizumab (Avastin) during and after chemotherapy were 52% less likely to have progression of their disease than were patients given placebo.
The absolute difference in median progression-free survival was 4 months, according to results reported at the annual meeting of the American Society of Clinical Oncology. Interim overall survival results also favored the drug.
"The OCEANS study is a positive study," lead investigator Dr. Carol Aghajanian said in a press briefing. The combination therapy "provides a clinically meaningful benefit in recurrent ovarian cancer."
"This regimen should be considered a new option for women with recurrent platinum-sensitive ovarian cancer, recommended Dr. Aghajanian, chief of the gynecologic medical oncology service at Memorial Sloan-Kettering Cancer Center in New York.
Patients with advanced ovarian cancer often receive multiple lines of chemotherapy, noted Dr. Andrew Seidman, who moderated the press briefing. "There are many chapters in the story, so to speak, and I think the ability to prolong each and every chapter in this disease will, in my estimation, make the story longer – that is, ultimately improve survival. These trial results are certainly an important step in this direction."
Maintenance therapy with a biologic agent also allows patients to avoid the harsh adverse effects of chemotherapy, added Dr. Seidman, an attending physician for breast cancer medicine at Memorial Sloan-Kettering and professor of medicine at Weill Cornell Medical College, New York.
"With the ... prolongation in the time to progression, patients can live with more time to lead full and active lives, in the absence of chemotherapy," he said. "It’s also comforting to see that there were no new safety signals in this trial, and in particular, [no] bowel perforations."
The 484 women enrolled in the trial had platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer; had not received any chemotherapy for their recurrence; and had measurable disease.
They were assigned in equal numbers to receive 6-10 cycles of standard chemotherapy (carboplatin and gemcitabine) plus either bevacizumab, a monoclonal antibody to vascular endothelial growth factor given at a dose of 15 mg/kg every 3 weeks, or a placebo concurrently, followed by single-agent bevacizumab or placebo, respectively.
The bevacizumab dose was based on that showing activity in single-arm phase II trials of the drug leading up to the OCEANS trial, according to Dr. Aghajanian. This dose has not been directly compared with lower doses in ovarian cancer.
Treatment continued until the time of progression, the trial’s primary end point, assessed using RECIST (Response Evaluation Criteria in Solid Tumors).
Trial results showed that the median number of cycles of chemotherapy received was six in each group. The median number of cycles of bevacizumab and placebo was 12 and 10, respectively.
After a median follow-up of 24 months, patients in the bevacizumab group had a slightly more than one-half reduction in the risk of progression relative to their counterparts in the placebo group as assessed by the investigators (hazard ratio, 0.48; P less than .0001).
Median progression-free survival was 12.4 months with bevacizumab, compared with 8.4 months with placebo. "The curves separate at 2 months and remain separated throughout," Dr. Aghajanian noted. The findings were similar when progression was instead ascertained by an independent review committee.
In addition, bevacizumab was associated with better progression-free survival across subgroups of patients stratified by factors such as the platinum-free interval before recurrence, age, and receipt of cytoreductive surgery for recurrence.
Results also showed that patients in the bevacizumab group had a comparatively higher objective response rate (78.5% vs. 57.4%, P less than .0001) and longer duration of response (10.4 vs. 7.4 months, P less than .0001).
Overall survival results are not yet mature, she cautioned. But an interim analysis also showed a trend favoring bevacizumab, with median overall survival of 35.5 months with the drug, compared with 29.9 months with placebo (hazard ratio, 0.75; P = .094).
"The safety data were reassuring and consistent with the known bevacizumab side effect profile," reported Dr. Aghajanian.
Specifically, patients in the bevacizumab group were comparatively more likely to experience grade 3 or higher hypertension (17% vs. less than 1%) and proteinuria (9% vs. 1%). And 1% of patients in that group experienced reversible posterior leukoencephalopathy syndrome, but it resolved in all cases after drug discontinuation.
Of particular note, none of the bevacizumab-treated patients experienced gastrointestinal perforation during treatment, she pointed out. And none experienced previously undescribed adverse effects.