4 MONTHS INCREASE IN PFS AT WHAT COST?

Bevacizumab prolongs progression-free survival for women with advanced ovarian cancers
16.06.10
Category: Scientific News

There is a need for mature overall survival and quality-of-life results to understand the full effect of this study

Carboplatin and paclitaxel (CP) plus bevacizumab, followed by bevacizumab maintenance, may now offer another treatment option for women diagnosed with advanced epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer. Support for this regimen comes from an international phase III Gynecologic Oncology Group (GOG) study that demonstrated prolonged progression-free survival (PFS) with the addition of concomitant and maintenance bevacizumab to CP compared with CP alone in patients receiving frontline treatment for advanced ovarian cancer.

Bevacizumab is the first molecular targeted and first antiangiogenic agent to demonstrate benefit in this population. Dr Robert A Burger of Fox Chase Cancer Center presented results of the GOG-0218 study during Plenary Session at the 45th ASCO Annual Meeting (Chicago, 4-8 July 2010).

The double-blind, placebo-controlled, phase III trial enrolled nearly 1,900 patients with chemotherapy-naive stage III or IV epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer in the United States, Canada, South Korea, and Japan. All women underwent abdominal surgery for staging and maximal tumor debulking before being randomly assigned to one of three treatment arms: (1) CP plus placebo during the induction phase (cycles 1 to 6), followed by placebo maintenance (cycles 7 to 22); (2) CP plus concurrent bevacizumab during induction, followed by placebo maintenance; and (3) CP plus concurrent bevacizumab during induction, followed by bevacizumab maintenance. Bevacizumab was not administered during the first 21-day induction cycle so as to limit postsurgical bleeding complications. The entire treatment schedule took 15 months to complete.

Although overall survival was originally selected as the primary endpoint, this was changed to PFS to accord with international consensus as a more appropriate endpoint for frontline phase III trials in this patient population, as well as pressure by patients to unblind their treatment assignment in the event of disease progression. The investigators monitored disease progression based on radiographic evidence, CA-125 measurements, and global clinical deterioration. Overall survival, safety, and quality of life comprised the secondary endpoints.

Patients had a median age of 60, 84% were white, and 93% had a GOG performance status of 0 or 1. Despite attempts at maximal tumor debulking, only 34% had optimally debulked stage III disease; 40% had stage III suboptimally debulked disease; 26% had stage IV disease.

After a median follow-up of 17.4 months (range: 0 to 50.7 months), PFS was signicantly prolonged by 3.8 months with CP plus concomitant and maintenance bevacizumab compared with CP alone (14.1 months compared with 10.3 months, respectively; p < 0.0001). Moreover, all patient subgroups analyzed exhibited consistent improvements in PFS with the concomitant and maintenance bevacizumab regimen regardless of disease stage, performance status, and patient age.

No significant difference in PFS was observed between the arm that received CP plus concomitant bevacizumab only and the arm that received CP alone. The investigators have not yet discerned any differences in overall survival across the three arms; however, the survival data are not yet mature. At the time of data analysis, median overall survival ranged from 38.7 to 39.7 months, and 1-year survival ranged from 90.4% to 91.3%.

The addition of bevacizumab to CP appeared well tolerated, with no unexpected adverse events observed. Although hypertension occurred significantly more often in the bevacizumab arms compared with the control arm (p < 0.05), the incidences of all other adverse events were similar across arms, including neutropenia and thromboembolic events. Dr. Burger emphasized that gastrointestinal perforation events did not markedly increase with use of bevacizumab (2.6% to 2.8% in the bevacizumab arms compared with 1.2% in the control arm), and bleeding complications were rare in all arms (0.8% to 2.4%).

As discussant, Dr Elizabeth A Eisenhauer of the National Cancer Institute of Canada Clinical Trials Group and Queen’s University, Canada, offered several insights on the GOG-0218 outcomes. According Dr Eisenhauer, a PFS gain of only 3.8 months may not be meaningful to patients and there is a need for mature overall survival and quality-of-life results to understand the full effect of this study.