Avastin Regimen Shows Survival Trend in Phase 3 Ovarian Cancer Trial

Treatment with Avastin (bevacizumab) plus chemotherapy resulted in an improvement in overall survival (OS) of nearly five months compared with chemotherapy alone for women with platinum-sensitive recurrent ovarian cancer, according to results from the phase 3 GOG0213 trial presented at the 2015 Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.

The clinical trial results mark the first time a phase 3 study has shown improvement in OS for this patient population. Although findings from GOG0213 narrowly missed statistical significance, they build upon evidence supporting the use of Avastin in recurrent platinum-sensitive settings. In November 2014, the Food and Drug Administration (FDA) approved Avastin in combination with chemotherapy for the treatment of women with platinum-resistant recurrent ovarian cancer based upon an improvement in progression-free survival (PFS).

Lead author Robert L. Coleman, professor and vice chair of Clinical Research, Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, is pleased with the findings. “Even though we narrowly missed statistical significance, we saw a strong trend toward improved overall survival,” Coleman says.

Coleman indicated the trial would address several persistent questions in the treatment of women with these cancers. “Platinum-based doublets have become a standard of care for women with platinum-sensitive recurrent ovarian cancer, but the roles of secondary bevacizumab and secondary surgery have yet to be defined,” he said at the conference. “There’s intense interest surrounding both of these issues, as well as a desire to understand bevacizumab’s effect on overall survival when other trials have largely assessed progression-free survival.

GOG0213, which was initiated in December 2007, accrued 674 women with epithelial ovarian, primary peritoneal or fallopian tube cancers whose disease recurred after frontline or maintenance therapy that could have included prior Avastin. Nearly 70 percent of the participants were aged 50 to 69 years.

The study’s primary objective was to examine the role of Avastin in combination with paclitaxel plus carboplatin followed by maintenance with Avastin versus the same chemotherapy doublet. Both arms received paclitaxel and carboplatin for six cycles, and the study arm patients then continued with Avastin maintenance. Chemotherapy randomization terminated in August 2011 and matured for OS in November 2014.

Median OS for patients in the Avastin treatment group was 42.2 months, compared with 37.3 months for those receiving chemotherapy alone. PFS improved by nearly 3.5 months with Avastin: 13.8 months compared with 10.4 months for patients on chemotherapy alone. The risk reduction for progression and death with Avastin were 39 percent and 17 percent, respectively.

The study’s second objective is to examine the role of secondary cytoreduction before chemotherapy is initiated. Enrollment for this objective is ongoing; accordingly, results are pending. Both objectives share the same primary endpoint of OS; secondary endpoints for both include safety and toxicity, PFS, and intervention-dependent quality of life (QoL).

During the trial, patients were randomized to chemotherapy or chemotherapy plus Avastin. Each treatment arm had equal representation among three strata that had been prospectively defined: cytoreductive surgery as part of the study’s second objective (8 percent); prior platinum-free interval (6 to 12 months, 31 percent; more than 12 months, 69 percent); and previous Avastin exposure (yes, 10 percent; no, 90 percent).

Adverse events (AEs) increased with the Avastin-containing regimen but all remained within expected parameters.

During his presentation, Coleman compared outcomes from six studies that had sought to improve treatments for women with recurrent ovarian cancer. Improvements in PFS have established platinum-based doublets as the standard of care but none of the studies showed an improvement in OS.

Similarly, Avastin enhanced PFS when added to gemcitabine and carboplatin compared with the chemotherapy combination alone in the phase 3 OCEANS trial but did not demonstrate a statistically significant OS improvement.

Coleman answered the question of whether he believes GOG 213’s findings are already practice changing. “Yes, because we have pushed the median survival past 40 months in patients with recurrent disease,” he says. “We’re starting to find strategies and treatments that ultimately are quite strong.”