Efficacy and Tolerability of Eribulin Plus Lapatinib in Patients With Metastatic Breast Cancer (E-VITA)
Status:
Terminated
Trial end date:
2015-03-01
Target enrollment:
Participant gender:
Summary
- Lapatinib in combination with capecitabine has been approved for the treatment of women
with HER-2-positive advanced breast cancer that have progressed after anthracycline-,
taxane-, and trastuzumab-containing therapies. The use of this combination is limited by
overlapping toxicity such as diarrhea and cutaneous side effects.
- A significant number of patients receive today capecitabine with trastuzumab as first-
or second-line treatment. Therefore, other combinations of lapatinib with less toxic
cytotoxic agents are needed.
- Eribulin mesylate (E7389) is a synthetic analog of Halichondrin B (HalB), a large
polyether macrolide isolated from a marine sponge. Eribulin is a mechanistically unique
antagonist of microtubule dynamics among tubulin-targeted agents, leading to inhibition
of microtubule growth in the absence of effects on microtubule shortening, and formation
of non- productive tubulin aggregates.
- Eribulin mesylate at a dose of 1.4 mg/m² given on day 1, 8 every 3 weeks has shown
better overall survival by 2.5 months compared to treatment of physicians choice in
patients with locally advanced or metastatic breast cancer who were previously treated
for 2-5 lines with anthracyclines, taxanes, and capecitabine (EMBRACE study).
- The most frequently reported eribulin-related AEs were asthenia/fatigue (65%), alopecia
(60%), neutropenia (60%), nausea (44%), anemia (28%), pyrexia (23%), leucopenia (22%),
anorexia (21%), constipation (19%), vomiting (18%), and peripheral neuropathy (5.5%;
only grade 3). Grade 4 neutropenia occurred in 32% of patients, and febrile neutropenia
occurred in 5.5% of patients. The frequency of all other grade 3/4 AEs was less than 3%.
This toxicity profile does not overlap with that of lapatinib.
- There is uncertainty in how far a once every 3 week schedule of eribulin mesylate at a
dose of 2.0 mg/m² would be better tolerated. Several phase II studies are currently
conducted in various non-breast cancer indications to compare the d1+8 q d21 with a d1 q
d21 schedule.
- The aim of this randomized phase II study is to compare the efficacy and tolerability of
two dose-schedules of eribulin plus lapatinib in HER2-positive breast cancer,
pre-treated with trastuzumab in the adjuvant and/or metastatic setting.