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The median progression-free survival (PFS) was 5.5 months for patients randomized to receive ixabepilone and bevacizumab, versus 2.2 months for patients assigned to ixabepilone alone (P < .001). The median overall survival (OS) was 10 months and 6 months, respectively (P = .006), although the trial was underpowered to detect OS differences.
These results were presented in a late-breaking abstract session at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 11570).
“Therapeutic options for platinum- and taxane-resistant ovarian cancer are limited, and, unfortunately, median overall survival in this population is only approximately 12 months. It’s obvious that additional treatment strategies are warranted,” Dana M. Roque, MD, of the University of Maryland in Baltimore, said when presenting the results.
Study rationale and details
Dr. Roque explained that ixabepilone is an epothilone B analog that may retain activity in patients with taxane-resistant disease. She and her colleagues previously found, in a retrospective study, that ixabepilone, with or without bevacizumab, showed “promising” activity with acceptable toxicity in patients with recurrent uterine or ovarian/primary peritoneal/fallopian tube cancers.
At SGO 2021, Dr. Roque reported results of a prospective, phase 2 trial of 76 patients randomized to ixabepilone alone or in combination with bevacizumab.
Patients with measurable recurrent or persistent platinum-resistant or refractory epithelial nonmucinous ovarian, fallopian tube, or primary peritoneal cancers were enrolled. The patients had to have received at least three prior cycles of paclitaxel, but there was no upper limit on prior lines of therapy, including bevacizumab.
After stratification by prior bevacizumab and study site, the patients were randomly assigned to either ixabepilone monotherapy at a dose of 20 mg/m2 on days 1, 8, and 15 of every 28-day cycle (n = 37), or the same dose of ixabepilone plus bevacizumab at 10 mg/kg on days 1 and 15 every 28 days (n = 39).
Most patients in each arm – 78% in the monotherapy arm and 87% in the combination arm – had serous tumors, with the remaining patients having carcinosarcomas or other, unspecified histologies.
Efficacy and safety
The overall response rate was 33% with the combination and 8% with ixabepilone monotherapy. There were no correlations between TUBB3 staining and either responses or durable disease control.
As noted before, PFS and OS were significantly better with the combination. Neither PFS nor OS were influenced by prior bevacizumab use, heavy pretreatment, poor performance status, nonserous histology, or age.
Dose-limiting toxicities with the combination included peripheral neuropathy, neutropenia, and fatigue. There was one bowel perforation in a patient on the combination.
Patients assigned to the combination were significantly more likely to experience hypertension (36% vs. 8%, P = .005) and peripheral neuropathy (51% vs. 19%, P = .004). However, there were no differences in serious adverse events between the treatment arms.
Dr. Roque acknowledged that this study was limited by incomplete immunohistochemistry data, a lack of stratification by extent of prior taxane exposure in the recurrent setting, a lack of a bevacizumab control arm, and underpowering to detect OS differences.
Comparison with AURELIA
Dr. Roque and the invited discussant, Thomas J. Herzog, MD, of the University of Cincinnati Cancer Center in Ohio, both compared results of the current trial to results from the AURELIA trial, in which patients with platinum-resistant ovarian cancers were randomized to chemotherapy with or without bevacizumab.
According to AURELIA data published in 2014, the ORR with the bevacizumab-chemotherapy combination was 27%, compared with 33% with ixabepilone-bevacizumab in the current trial. The median PFS was 6.7 months and 5.5 months, respectively, and the median OS was 16.6 months and 10 months, respectively.
An analysis of AURELIA data published in 2015 suggested that outcomes were even better for patients who received paclitaxel plus bevacizumab. This group had an ORR of 53.3%, a median PFS of 10.4 months, and a median OS of 22.4 months.
Though the current study’s results don’t appear to measure up to results from AURELIA, Dr. Herzog called the current study “very exciting.”
“The efficacy looks very promising,” he said. “They even showed efficacy for OS that looked very interesting, even though that was underpowered.”
Dr. Herzog did note the lack of a companion diagnostic because the TUBB3 staining did not correlate with response. He also said the trial was limited by the lack of a bevacizumab control arm. Furthermore, because of the relatively small sample size in the combination group (n = 39), the lower bound of the confidence interval for ORR includes response rates typically seen with conventional therapies.
“I do think that the combination does make sense biologically, so I’d like to see more data on that,” he concluded.
The trial was sponsored by Yale University, with study drug supplied by R-Pharm-US. Dr. Roque reported no conflicts of interest. Dr. Herzog disclosed serving as a scientific advisor to several companies, including Genentech, maker of bevacizumab.
The median progression-free survival (PFS) was 5.5 months for patients randomized to receive ixabepilone and bevacizumab, versus 2.2 months for patients assigned to ixabepilone alone (P < .001). The median overall survival (OS) was 10 months and 6 months, respectively (P = .006), although the trial was underpowered to detect OS differences.
These results were presented in a late-breaking abstract session at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 11570).
“Therapeutic options for platinum- and taxane-resistant ovarian cancer are limited, and, unfortunately, median overall survival in this population is only approximately 12 months. It’s obvious that additional treatment strategies are warranted,” Dana M. Roque, MD, of the University of Maryland in Baltimore, said when presenting the results.
Study rationale and details
Dr. Roque explained that ixabepilone is an epothilone B analog that may retain activity in patients with taxane-resistant disease. She and her colleagues previously found, in a retrospective study, that ixabepilone, with or without bevacizumab, showed “promising” activity with acceptable toxicity in patients with recurrent uterine or ovarian/primary peritoneal/fallopian tube cancers.
At SGO 2021, Dr. Roque reported results of a prospective, phase 2 trial of 76 patients randomized to ixabepilone alone or in combination with bevacizumab.
Patients with measurable recurrent or persistent platinum-resistant or refractory epithelial nonmucinous ovarian, fallopian tube, or primary peritoneal cancers were enrolled. The patients had to have received at least three prior cycles of paclitaxel, but there was no upper limit on prior lines of therapy, including bevacizumab.
After stratification by prior bevacizumab and study site, the patients were randomly assigned to either ixabepilone monotherapy at a dose of 20 mg/m2 on days 1, 8, and 15 of every 28-day cycle (n = 37), or the same dose of ixabepilone plus bevacizumab at 10 mg/kg on days 1 and 15 every 28 days (n = 39).
Most patients in each arm – 78% in the monotherapy arm and 87% in the combination arm – had serous tumors, with the remaining patients having carcinosarcomas or other, unspecified histologies.
Efficacy and safety
The overall response rate was 33% with the combination and 8% with ixabepilone monotherapy. There were no correlations between TUBB3 staining and either responses or durable disease control.
As noted before, PFS and OS were significantly better with the combination. Neither PFS nor OS were influenced by prior bevacizumab use, heavy pretreatment, poor performance status, nonserous histology, or age.
Dose-limiting toxicities with the combination included peripheral neuropathy, neutropenia, and fatigue. There was one bowel perforation in a patient on the combination.
Patients assigned to the combination were significantly more likely to experience hypertension (36% vs. 8%, P = .005) and peripheral neuropathy (51% vs. 19%, P = .004). However, there were no differences in serious adverse events between the treatment arms.
Dr. Roque acknowledged that this study was limited by incomplete immunohistochemistry data, a lack of stratification by extent of prior taxane exposure in the recurrent setting, a lack of a bevacizumab control arm, and underpowering to detect OS differences.
Comparison with AURELIA
Dr. Roque and the invited discussant, Thomas J. Herzog, MD, of the University of Cincinnati Cancer Center in Ohio, both compared results of the current trial to results from the AURELIA trial, in which patients with platinum-resistant ovarian cancers were randomized to chemotherapy with or without bevacizumab.
According to AURELIA data published in 2014, the ORR with the bevacizumab-chemotherapy combination was 27%, compared with 33% with ixabepilone-bevacizumab in the current trial. The median PFS was 6.7 months and 5.5 months, respectively, and the median OS was 16.6 months and 10 months, respectively.
An analysis of AURELIA data published in 2015 suggested that outcomes were even better for patients who received paclitaxel plus bevacizumab. This group had an ORR of 53.3%, a median PFS of 10.4 months, and a median OS of 22.4 months.
Though the current study’s results don’t appear to measure up to results from AURELIA, Dr. Herzog called the current study “very exciting.”
“The efficacy looks very promising,” he said. “They even showed efficacy for OS that looked very interesting, even though that was underpowered.”
Dr. Herzog did note the lack of a companion diagnostic because the TUBB3 staining did not correlate with response. He also said the trial was limited by the lack of a bevacizumab control arm. Furthermore, because of the relatively small sample size in the combination group (n = 39), the lower bound of the confidence interval for ORR includes response rates typically seen with conventional therapies.
“I do think that the combination does make sense biologically, so I’d like to see more data on that,” he concluded.
The trial was sponsored by Yale University, with study drug supplied by R-Pharm-US. Dr. Roque reported no conflicts of interest. Dr. Herzog disclosed serving as a scientific advisor to several companies, including Genentech, maker of bevacizumab.
The median progression-free survival (PFS) was 5.5 months for patients randomized to receive ixabepilone and bevacizumab, versus 2.2 months for patients assigned to ixabepilone alone (P < .001). The median overall survival (OS) was 10 months and 6 months, respectively (P = .006), although the trial was underpowered to detect OS differences.
These results were presented in a late-breaking abstract session at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 11570).
“Therapeutic options for platinum- and taxane-resistant ovarian cancer are limited, and, unfortunately, median overall survival in this population is only approximately 12 months. It’s obvious that additional treatment strategies are warranted,” Dana M. Roque, MD, of the University of Maryland in Baltimore, said when presenting the results.
Study rationale and details
Dr. Roque explained that ixabepilone is an epothilone B analog that may retain activity in patients with taxane-resistant disease. She and her colleagues previously found, in a retrospective study, that ixabepilone, with or without bevacizumab, showed “promising” activity with acceptable toxicity in patients with recurrent uterine or ovarian/primary peritoneal/fallopian tube cancers.
At SGO 2021, Dr. Roque reported results of a prospective, phase 2 trial of 76 patients randomized to ixabepilone alone or in combination with bevacizumab.
Patients with measurable recurrent or persistent platinum-resistant or refractory epithelial nonmucinous ovarian, fallopian tube, or primary peritoneal cancers were enrolled. The patients had to have received at least three prior cycles of paclitaxel, but there was no upper limit on prior lines of therapy, including bevacizumab.
After stratification by prior bevacizumab and study site, the patients were randomly assigned to either ixabepilone monotherapy at a dose of 20 mg/m2 on days 1, 8, and 15 of every 28-day cycle (n = 37), or the same dose of ixabepilone plus bevacizumab at 10 mg/kg on days 1 and 15 every 28 days (n = 39).
Most patients in each arm – 78% in the monotherapy arm and 87% in the combination arm – had serous tumors, with the remaining patients having carcinosarcomas or other, unspecified histologies.
Efficacy and safety
The overall response rate was 33% with the combination and 8% with ixabepilone monotherapy. There were no correlations between TUBB3 staining and either responses or durable disease control.
As noted before, PFS and OS were significantly better with the combination. Neither PFS nor OS were influenced by prior bevacizumab use, heavy pretreatment, poor performance status, nonserous histology, or age.
Dose-limiting toxicities with the combination included peripheral neuropathy, neutropenia, and fatigue. There was one bowel perforation in a patient on the combination.
Patients assigned to the combination were significantly more likely to experience hypertension (36% vs. 8%, P = .005) and peripheral neuropathy (51% vs. 19%, P = .004). However, there were no differences in serious adverse events between the treatment arms.
Dr. Roque acknowledged that this study was limited by incomplete immunohistochemistry data, a lack of stratification by extent of prior taxane exposure in the recurrent setting, a lack of a bevacizumab control arm, and underpowering to detect OS differences.
Comparison with AURELIA
Dr. Roque and the invited discussant, Thomas J. Herzog, MD, of the University of Cincinnati Cancer Center in Ohio, both compared results of the current trial to results from the AURELIA trial, in which patients with platinum-resistant ovarian cancers were randomized to chemotherapy with or without bevacizumab.
According to AURELIA data published in 2014, the ORR with the bevacizumab-chemotherapy combination was 27%, compared with 33% with ixabepilone-bevacizumab in the current trial. The median PFS was 6.7 months and 5.5 months, respectively, and the median OS was 16.6 months and 10 months, respectively.
An analysis of AURELIA data published in 2015 suggested that outcomes were even better for patients who received paclitaxel plus bevacizumab. This group had an ORR of 53.3%, a median PFS of 10.4 months, and a median OS of 22.4 months.
Though the current study’s results don’t appear to measure up to results from AURELIA, Dr. Herzog called the current study “very exciting.”
“The efficacy looks very promising,” he said. “They even showed efficacy for OS that looked very interesting, even though that was underpowered.”
Dr. Herzog did note the lack of a companion diagnostic because the TUBB3 staining did not correlate with response. He also said the trial was limited by the lack of a bevacizumab control arm. Furthermore, because of the relatively small sample size in the combination group (n = 39), the lower bound of the confidence interval for ORR includes response rates typically seen with conventional therapies.
“I do think that the combination does make sense biologically, so I’d like to see more data on that,” he concluded.
The trial was sponsored by Yale University, with study drug supplied by R-Pharm-US. Dr. Roque reported no conflicts of interest. Dr. Herzog disclosed serving as a scientific advisor to several companies, including Genentech, maker of bevacizumab.
FROM SGO 2021