Randomized Phase III Trial of Ixabepilone Plus Capecitabine Versus Capecitabine in Patients With Metastatic Breast Cancer Previously Treated With an Anthracycline and a Taxane

Abstract

This study confirmed a previous trial demonstrating improved PFS and response for the ixabepilone-capecitabine combination compared with capecitabine alone, although this did not result in improved survival.

Eribulin monotherapy in a patient with heavily pretreated metastatic breast cancer: Case study and review of the literature

“…Grade 3/4 neutropenia was more common in the combination arm (68% vs. 11% and 73% vs. 9%), as well as grade 3/4 leukopenia (57% vs. 6% and 63% vs. 7%), anemia (10% vs. 4% and 5% vs. 4%), and thrombocytopenia (8% vs. 4% and 6% vs. 3%) [26,27] Similarly, grade 3/4 peripheral neuropathy was more common in the combination arm (23% vs. 0% and 25% vs. 1%) [26] (2129}.…”

“…The most common grade 3/4 AEs were neutropenia (54%), leukopenia (49%), peripheral sensory neuropathy (14%), fatigue/asthenia (14%), anemia (8%), thrombocytopenia (8%), myalgia/arthralgia (8%), and stomatitis/mucositis (7%) [25] . In 2 phase 3 trials comparing ixabepilone plus capecitabine with capecitabine monotherapy in patients with locally advanced/metastatic breast cancer who were pretreated with taxanes and anthracyclines (one study included 752 patients and the other 1,221 patients), the ixabepilone/capecitabine combination significantly improved ORR (35% vs. 14% and 43% vs. 29%, P <0.0001 for both) and median PFS (5.8 vs. 4.2 months; P = 0.0003 and 6.2 vs. 4.2 months; P = 0.0005, respectively) [26,27] . In both studies, the combination was not associated with a statistically significant improvement in OS (12.9 vs. 11.1 months; P = 0.19 and 16.4 vs. 15.6 months; P = 0.1162) [23,27] .…”

“…Other frequently reported non-hematologic grade 3/4 AEs included hand-foot syndrome (18% vs. 17% and 21% vs. 20%), fatigue (9% vs. 3% and 12% vs. 3%), myalgia (8% vs. 0.3% and 4% vs. 0%), asthenia (7% vs. 0.8% and 6% vs. 1%), and diarrhea (6% vs. % 9% and 7% vs. 9%) [26,27] Several classes of endocrine therapy are options for patients with heavily pretreated ER-positive metastatic breast cancer, although resistance is likely to develop [6] . Up to 3 different endocrine therapies may be attempted if progression or symptomatic visceral disease develops or toxicity is unacceptable [7] .…”

Systemic Treatment Approaches in her2-Negative Advanced Breast Cancer—Guidance on the Guidelines

“…Ixabepilone has been evaluated as a single agent 56 and in combination with capecitabine in patients previously treated with anthracycline and taxane therapy [87][88][89] . A phase iii trial noted that, compared with capecitabine alone, ixabepilone-capecitabine was associated with improved rr (43% vs. 29%) and pfs (6.2 months vs. 4.2 months), but no improvement in os (16.4 months vs. 15.6 months) 88 . Grade 3 or 4 neuropathy occurred in 24% of patients treated with combination therapy, but was reported to be reversible.…”

How to overcome ATP-binding cassette drug efflux transporter-mediated drug resistance?

“…They show a diverse susceptibility profile to P-gp mediated resistance, with ixabepilone the most and sagopilone the less affected by P-gp overexpression [142,143] . Currently, ixabepilone is FDA approved for the treatment of metastatic breast cancer and has been tested in phase III clinical trials in combination with capecitabine [144][145][146] .…”