Avastin Gains Expanded FDA Approval for Platinum-Sensitive Ovarian Cancer
The FDA expanded Avastin's approval to include patients with platinum-sensitive ovarian cancer.
BY Tony Hagen
PUBLISHED December 07, 2016
Avastin (bevacizumab) gained an expanded FDA approval to treat patients with platinum-sensitive recurrent ovarian cancer as a part of a combination regimen with chemotherapy followed by continued use of the angiogenesis inhibitor, according to the drug developer, Genentech.
The approval is based on results from two randomized controlled phase 3 studies, GOG-0213 and OCEANS. GOG-0213 demonstrated that adding Avastin to chemotherapy led to a non-statistically significant median overall survival (OS) difference of five months compared with chemotherapy alone (42.6 months vs 37.3 months, respectively; HR, 0.84).
Both studies demonstrated a significant improvement in progression-free survival (PFS). In the GOG-0213 study, median PFS improved by 3.4 months with the addition of Avastin to chemotherapy compared to chemotherapy alone (13.8 months vs 10.4 months, respectively), according to Genentech.
The OCEANS study, which enrolled 484 women, showed a median PFS improvement of four months for Avastin with chemotherapy versus placebo plus chemotherapy (12.4 months vs 8.4 months, respectively). The secondary endpoint of OS did not show statistically significant improvement.
In both trials, the Avastin-containing regimens resulted in higher objective response rates (ORRs). The ORR with Avastin was 78 percent in both studies; for the chemotherapy arms, the ORR was 56 percent in GOG-0213 and 57 percent in OCEANS.
The approval gives women with recurrent platinum-sensitive ovarian cancer a treatment option that is superior to chemotherapy alone, said Sandra Horning, M.D., chief medical officer and head of Global Product Development for Genentech, touting the five-month improvement in OS. Woman are considered to have a platinum-sensitive form of the disease if a relapse occurs six months or longer following the last treatment with a platinum-based chemotherapy.
Specifically, the new indication supports the use of Avastin either in combination with carboplatin and paclitaxel or in combination with carboplatin and gemcitabine chemotherapy, followed by Avastin alone, for patients with platinum-sensitive recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer, Genentech said.
In November 2014, Avastin was approved in the United States for the treatment of women with platinum-resistant recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer in combination with paclitaxel, pegylated liposomal doxorubicin or topotecan chemotherapy. Women are considered to have a platinum-resistant form of the disease if a relapse occurs less than six months after the last treatment with a platinum-based chemotherapy.
For platinum-sensitive disease, the company said adverse events in both studies were consistent with those seen in previous trials of Avastin across tumor types for approved indications, but also included low white blood cell count with fever, low sodium level in the blood, pain in extremity, low platelet count, too much protein in the urine, high blood pressure, and headache.
First announced in March 2015, the GOG-0213 results marked the first time a phase 3 study has shown improvement in OS for the platinum-sensitive patient population. Although findings from GOG-0213 narrowly missed statistical significance, they built upon evidence supporting the use of Avastin in recurrent platinum-sensitive settings.
“Even though we narrowly missed statistical significance, we saw a strong trend toward improved overall survival,” lead author Robert L. Coleman, M.D., said at the time. Coleman is professor and vice chair of Clinical Research, Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center.
GOG0213, which was initiated in December 2007, accrued 673 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 (15 mg/kg) in combination with paclitaxel (175 mg/m2) plus carboplatin (AUC5) 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.
In a prior interview with CURE, Coleman said GOG-0213’s findings would be practice changing. “We have pushed the median survival past 40 months in patients with recurrent disease,” he said. “We’re starting to find strategies and treatments that ultimately are quite strong.”