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Ixabepilone remains inferior to paclitaxel in metastatic disease
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SAN ANTONIO — Ixabepilone appeared inferior to paclitaxel and nab-paclitaxel in terms of OS among patients with locally recurrent or metastatic breast cancer, according to long-term follow-up of a phase 3 clinical trial presented at the San Antonio Breast Cancer Symposium.
Earlier results of the CALGB 40502 trial showed ixabepilone (Ixempra, R-Pharm US) appeared inferior to paclitaxel in terms of PFS. Nab-paclitaxel also did not demonstrate superiority over paclitaxel, with a trend toward inferiority.
Hope S. Rugo, MD, clinical professor of medicine at University of California San Francisco Comprehensive Cancer Center, presented long-term follow-up findings from the trial, with an unplanned subset analysis in hormone receptor-positive and triple-negative breast cancers.
Researchers evaluated weekly paclitaxel 90 mg/m2 compared with weekly nab-paclitaxel 150 mg/m2 or weekly ixabepilone 16 mg/m2 with or without 10 mg/kg bevacizumab (Avastin, Genentech) every 2 weeks as first-line therapy for locally recurrent or metastatic breast cancer.
The analysis included 283 patients in the paclitaxel arm who served as controls, as well as 271 patients in the nab-paclitaxel and 245 patients in the ixabepilone experimental arms.
“The primary objective was to compare PFS in the control and experimental arms separately,” Rugo said. “We are updating PFS and OS data with 4 years of additional follow-up.”
The current analysis includes findings for 70 additional PFS events, for a total of 732.
PFS results showed a median duration of 10.8 months (95% CI, 9.6-12) in the paclitaxel group, 9.2 months (95% CI, 7.9-10.1) in the nab-paclitaxel arm, and 7.4 months (95% CI, 6.3-8.3) for ixabepilone.
The PFS comparison between nab-paclitaxel and paclitaxel showed that these two treatments were similar (HR = 1.13; 95% CI, 0.94-1.34). However, paclitaxel demonstrated superiority in this outcome compared with ixabepilone (HR = 1.22; 95% CI, 1.11-1.33).
“Both paclitaxel and nab-paclitaxel were better than ixabepilone,” Rugo said.
Among 201 patients with triple-negative disease, PFS was 6.4 months in the paclitaxel group, 7.4 months for nab-paclitaxel and 5.6 months for ixabepilone. Comparison of paclitaxel and nab-paclitaxel showed a trend toward improvement for the latter (HR = 0.79; 95% CI, 0.55-1.12).
“What you can see is that, numerically, nab-paclitaxel has 1 month longer PFS than paclitaxel,” Rugo said. “But, we are not powered to see statistically significant differences in this post-hoc analysis. Ixabepilone, however, remains inferior.”
Researchers calculate an HR of 1.39 (95% CI, 0.99-1.96) for PFS for ixabepilone compared with paclitaxel in this subgroup.
A similar trend occurred among 546 patients with hormone receptor-positive, HER-2-negative disease. In this subgroup, median PF was 12.2 months with paclitaxel, 9.6 months with nab-paclitaxel and 8 months with ixabepilone. Neither nab-paclitaxel (HR = 1.29; 95% CI, 1.04-1.59) nor ixabepilone (HR = 1.5; 95% CI, 1.21-1.86) improved PFS outcomes over paclitaxel in this subgroup.
“You can see that paclitaxel results in the numerically longest PFS, with relatively similar results in nab-paclitaxel and ixabepilone,” Rugo said.
Median OS in the triple-negative cohort reached 21 months with nab-paclitaxel, and was 15.3 months with paclitaxel and 15.1 months with ixabepilone.
“Again, we aren’t powered to see any statistically significant differences here,” Rugo said.
In the hormone receptor-positive population, the longest OS was in the paclitaxel group, at 33.2 months
“OS for nab-paclitaxel and ixabepilone were relatively similar with 1-month difference,” Rugo said.
For overall response rates, paclitaxel (38%) and nab-paclitaxel (34%) demonstrated similar outcomes that were superior to ixabepilone (27%; P = .0048).
“Interestingly, there was no difference in terms of the overall response rates between paclitaxel and nab-paclitaxel based on hormone receptor subset,” Rugo said.
Safety data indicated that nab-paclitaxel led to more grade 3 or worse adverse events (81% vs. paclitaxel, 60% vs. ixabepilone, 61%), dose modifications (68% vs. 42% vs. 38%) and discontinuations (26% vs. 14% vs. 23%) than the other therapies.
“In this updated analysis of weekly chemotherapy in patients with chemotherapy-naive metastatic breast cancer, ixabepilone continued to be inferior to paclitaxel for PFS,” Rugo concluded. “It is now also inferior for OS.”
She added that in the post-hoc subset analysis, paclitaxel bested the other two therapies for hormone receptor-positive disease, whereas suggestions of improved PFS and OS were reported for nab-paclitaxel compared to paclitaxel. – by Rob Volansky
Reference:
Rugo HS, et al. Abstract GS5-06. Presented at: San Antonio Breast Cancer Symposium; Dec. 5-9, 2017; San Antonio.
Disclosures: Rugo reports no relevant financial disclosures. Please see the abstract for all other authors’ relevant financial disclosures.