A presentation from the Society of Gynecologic Oncology 2021 Virtual Annual Meeting on Women’s Cancer highlighted data investigating the combination of ixabepilone and bevacizumab compared with ixabepilone monotherapy.
The combination of weekly ixabepilone plus biweekly bevacizumab (Avastin) was an effective and well-tolerated treatment option for patients with platinum-resistant or refractory ovarian, fallopian tube, or primary peritoneal cancer, according to data from a phase 2 trial (NCT03093155) presented at the Society of Gynecologic Oncology (SGO) 2021 Virtual Annual Meeting on Women’s Cancer.
More, the addition of bevacizumab to ixabepilone compared with ixabepilone monotherapy significantly improved a number of end points, including overall response rate (ORR), progression-free survival (PFS), and overall survival (OS).
“Heavily pre-treated platinum-resistant or refractory ovarian cancer lacks therapeutic options,” Dana M. Roque, MD, of the Greenebaum Comprehensive Cancer Center at the University of Maryland Medical Center, explained in her presentation of the data. “Weekly ixabepilone and biweekly bevacizumab is well-tolerated and effective, even in the platinum-refractory setting.”
Eligible patients had recurrent or persistent platinum-resistant/refractory epithelial ovarian, fallopian tube, or primary peritoneal cancer. Eligibility criteria included patients with measurable disease, tumor availability for immunohistochemistry, and 3 or more prior cycles of paclitaxel.
The study’s population was stratified by prior receipt of bevacizumab and study site, with patients being randomized to receive either ixabepilone monotherapy at 20mg/m2 on days 1, 8, and 15 of a 28-day cycle, or ixabepilone at 20 mg/m2 plus bevacizumab at 10 mg/kg on days 1 and 15 of the same cycle.
The primary end point of the trial was PFS, with secondary end points of OS, safety, and ORR.
Overall, 81 patients were screened at 2 sites in the United States, with 37 patients assigned to receive ixabepilone monotherapy and 39 assigned to receive ixabepilone plus bevacizumab. At the clinical data cut-off point, 29 (78%) and 28 (72%) patients in the ixabepilone monotherapy and ixabepilone plus bevacizumab groups had died, respectively.
Overall, the primary end point data suggest a benefit for patients in the ixabepilone plus bevacizumab group compared with the ixabepilone monotherapy group. PFS for the combination arm was 5.5 months compared with 2.2 months for the monotherapy arm (HR, 0.33; 95% CI, 0.19-0.55; P <.001).
Regarding data for the secondary end points, OS was recorded at 10.0 and 6.0 months for the combination and monotherapy arms, respectively (HR, 0.52; 95% CI, 0.31-0.87; P = .006). The ORR was 33% with ixabepilone plus bevacizumab versus 8% with ixabepilone monotherapy (P = .004).
“In the ancillary subgroup analyses, we found that prior receipt of bevacizumab did not influence progression-free survival or overall survival,” Roque explained. “We also found no effect of heavy pre-treatment, poor performance status, non-serous histology, or elderly status on these outcomes.”
While there were no new safety signals, the dose-limiting toxicities included peripheral neuropathy, neutropenia, and fatigue. Patients receiving the combination therapy were more likely to experience hypertension (36% versus 8%; P = .005) and peripheral neuropathy (51% versus 19%; P = .004) than patients in the monotherapy arm.
Limitations of the research included incomplete immunohistochemistry data, a lack of data focusing on the extent of prior taxane exposure for patients with recurrent disease, a lack of a control arm for analyzing bevacizumab, and inadequate power available to detect differences in OS.
The research team suggested an ixabepilone starting dose of 16 mg/m2 weekly should be considered to treat patients with this disease. More, future research should center its focus on predictive biomarkers as well as cost effectiveness of using biosimilars.
Roque DM, Siegel ER, Buza N, et al. Randomized phase II trial of weekly ixabepilone with or without biweekly bevacizumab for platinum-resistant or refractory ovarian, fallopian tube, primary peritoneal cancer. Presented at: 2021 Society of Gynecologic Oncology Virtual Annual Meeting on Women’s Cancer. Abstract 11570.