Combining Ixabepilone and Bevacizumab Appears Safe and Effective in Recurrent Uterine and Ovarian Cancers
In patients with recurrent/persistent uterine or ovarian/primary peritoneal/fallopian tube cancers, ixabepilone (Ixempra), especially with the addition of biweekly bevacizumab (Avastin), appears to be safe and effective, according to a study by Roque et al in Gynecologic Oncology. Further evaluation of this combination treatment is warranted to establish the optimal dose and schedule.
Despite improvements in first-line treatment approaches, ovarian and uterine cancers remain resistant to platinum and taxane-based therapies such as carboplatin and paclitaxel. New effective therapeutic approaches are needed for patients with advanced ovarian and uterine cancers. Growing interest lies in novel combinations of cytotoxic and antiangiogenic therapies. One potential therapeutic partnership is ixabepilone and bevacizumab. This regimen has been under investigation in other cancers such as advanced renal carcinoma but not in gynecologic cancers.
Thus, Roque and colleagues conducted a retrospective study examining the efficacy and safety of ixabepilone and bevacizumab in patients with ovarian/primary peritoneal/fallopian tube cancers. They also analyzed ixabepilone as a single agent in this patient population.
Study Details
Included in the study were 60 patients, 24 with uterine cancer and 36 with ovarian/fallopian tube/primary peritoneal cancer. Serous tumors represented the most common ovarian histology (50%) and were equally as common (37.5%) as endometrioid tumors among uterine tumors. Of the stage I uterine cancers, six were of endometrioid histology (two grade 1 tumors, one grade 2 tumor, and three grade 3 tumors), three were uterine serous cancers, and one was a heterologous carcinosarcoma. Prior to receiving ixabepilone with or without bevacizumab, patients had received a median of 3.5 (range = 1–10) prior lines of chemotherapy.
Patients completed a mean of 4.7 ± 2.9 cycles of ixabepilone; 66.7% (16/24) and 91.7% (33/36) of patients with uterine and ovarian cancers, respectively, received concurrent bevacizumab. The initial ixabepilone dose was 16 mg/m2 in most patients and 20 mg/m2 in some patients with uterine cancer and ovarian cancer. The median follow-up since diagnosis within this entire cohort was 3.66 years (range = 0.59–16.19).
Objective Response Rate of 41.7%
The objective response rate in patients with uterine cancers was 41.7%, with 12.5% achieving complete response and 29.2% achieving partial response. Disease stabilization occurred in an additional 20.3% of patients, and the median duration of response or disease stabilization was 7 months. The median progression-free and overall survival rates were 5.2 and 9.63 months, respectively. Progression-free survival was improved in patients who received concurrent bevacizumab (6.5 vs 3.0 months, respectively; P = .01; hazard ratio [HR] = 0.2; 95% confidence interval [CI] = 0.05–0.77), and overall survival was also longer (9.6 vs 4.2 months, respectively; P = .02, HR = 0.19, 95% CI = 0.05–0.74).
The overall response rate for ovarian cancers was 47.2%, with 11.1% of patients achieving complete response and 36.1% achieving partial response, and disease stabilization occurred in an additional 25%. There were insufficient numbers of ovarian cancer patients who received ixabepilone monotherapy to perform comparative analyses to ixabepilone with or without bevacizumab.
Toxicity associated with ixabepilone therapy that resulted in dose reduction included neuropathy (three patients). Toxicity associated with bevacizumab therapy that resulted in dose reduction included mucositis (one patient). Due to the acceptable level of toxicity associated with bevacizumab, consistent with previous studies, the investigators indicate that bevacizumab may have a role in the prolongation of progression-free survival in combination with cytotoxic therapy.
The investigators concluded, “We have shown that weekly ixabepilone, especially with the addition of biweekly bevacizumab, has promising activity and acceptable toxicity in patients with platinum- and taxane-resistant uterine and ovarian cancers. This regimen may warrant further prospective study for use in persistent or recurrent disease.”
Alessandro D. Santin, MD, of Yale University, is the corresponding author of this article in Gynecologic Oncology.
The authors reported no potential conflicts of interest.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
