Now, a phase II open-label study has demonstrated that a combination of the camptothecin analog irinotecan (Camptosar), and bevacizumab (Avastin) may be a safe and effective alternative in heavily pre-treated patients with recurrent ovarian cancer, including those with prior bevacizumab and topoisomerase inhibitor use.
In the study population of 29 women with recurrent ovarian cancer and prior exposure to topotecan (37.9%), and bevacizumab (44.6%), median progression-free survival (PFS) was 6.8 months and median overall survival (OS) was 15.4 months, Amy Tiersten, MD, of the Perlmutter Cancer at New York University Langone Medical Center in New York City and colleagues reported online in Gynecologic Oncology.
Twelve of 24 patients with measurable disease had a response lasting longer than 6 months. The most common grade 3/4 toxicity was diarrhea, and there were no treatment-related deaths.
“Our data not only supports the activity of repeated uses of bevacizumab, but also confirms the safety of this strategy in heavily pre-treated patients,” the researchers wrote. “This is very relevant, as insurance companies are increasingly reluctant to support subsequent access to bevacizumab if it has been used earlier in a patient’s disease course.”
A targeted inhibitor of vascular endothelial growth factor A (VEGFA), bevacizumab has been studied extensively in ovarian cancer and shown to improve PFS in both the upfront and recurrent setting, Tiersten and colleagues noted.
A partial response (PR) was documented in eight patients (30%), and at first assessment, 13 patients maintained stable disease (SD). While no complete response (CR) was observed, the objective response rate (ORR) was 27.6%, and the clinical benefit rate — a measure of CR, PR, and SD — was 72.4%.
“This is notable for this patient population with a median of five prior regimens and diminished reserve,” the researchers said.
“It is also notable that 40% of patients in this study had had prior bevacizumab and yet still responded to a regimen with bevacizumab,” another of the co-authors, Stephanie V. Blank, MD, of NYU Langone Medical Center, said via email. “This may make us rethink how we use bevacizumab in treating patients with recurrent ovarian cancer.
“Ovarian cancer is a very heterogeneous disease, and we need to approach it as such. This is not a one-size-fits-all type of condition. Research funding for ovarian cancer needs to happen to improve the management of patients with recurrent ovarian cancer. The more we learn, the more we can tailor therapies to specific patients.”
Despite excellent response rates with platinum-based chemotherapy, most patients present with advanced stage disease relapse, the researchers pointed out. Treatment for women who experience multiple recurrences is limited, particularly in the presence of platinum-resistant disease and diminished reserve.
This study builds on findings from the AURELIA trial, an open-label randomized phase III trial that assessed the safety and efficacy of adding bevacizumab to physician’s choice chemotherapy in 361 platinum-resistant ovarian cancer patients.
Despite the fact that only 7% of patients in that study had received prior bevacizumab, progression-free survival and toxicity findings were comparable.
“Our study expands on the chemotherapy combinations with bevacizumab studied in AURELIA in the treatment of recurrent ovarian cancer and offers a safe and efficacious alternative,” the researchers said. “Further, the preponderance of patients who had repeated treatment with bevacizumab in this study (>40%) provides much needed data to support a rationale for repeated use of bevacizumab later in a patient’s disease course.”
A total of 29 patients with a median age of 62 were enrolled in the study between April 2010 and May 2013. All had ovarian epithelial, fallopian tube, or primary peritoneal carcinoma that was recurrent, refractory, or persistent.
Of the 29 patients, 24 had measurable disease, and five had evaluable disease with two or more CA125 levels ≥ 50 at least one week apart. The median number of prior regimens the patients had received was five.
Patients received the topoisomerase 1 inhibitor irinotecan at 250 mg/m2, as per an earlier trial, and the antiangiogenic agent bevacizumab at 15 mg/kg every 21 days until disease progression or toxicity. After dose-related toxicity was observed in the first six enrolled patients, however, the initial dose of irinotecan was lowered to 175 mg/m2.
The median number of study cycles was seven. Every two cycles, the response was assessed by Response Evaluation Criteria in Solid Tumors (RECIST) or CA-125 criteria.
Ten patients (34.5%) were platinum-sensitive and had disease recurrence 6 months or longer after the last treatment with platinum-containing chemotherapy.
A total of 19 women (65.5%) were platinum-resistant and had recurrences within 6 months of the last platinum-containing regimen.
Limitations of the study include the fact that it was not designed to target a more homogenous population of platinum-resistant patients, the researchers said. “Arguably, [this] would have allowed us to see a stronger signal of activity.”
In addition, the design did not make it possible to compare the drug combination with single-agent irinotecan or to quantify the benefit of added bevacizumab.
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