Phase II study of the halichondrin B analog eribulin mesylate in patients with locally advanced or metastatic breast cancer previously treated with an anthracycline, a taxane, and capecitabine.
OBJECTIVE
The activity and safety of eribulin mesylate (E7389), a nontaxane microtubule dynamics inhibitor with a novel mechanism of action, were evaluated in patients with locally advanced or metastatic breast cancer previously treated with an anthracycline, taxane, and capecitabine.


METHODS
Eligible patients in this single-arm, open-label phase II study received eribulin mesylate (1.4 mg/m(2)) administered as a 2- to 5-minute intravenous infusion on days 1 and 8 of a 21-day cycle. The primary end point was objective response rate (ORR) assessed by independent review.


RESULTS
Of 299 enrolled patients who had received a median of four prior chemotherapy regimens, 291 received eribulin (for a median of four cycles). Of these, 269 patients met key inclusion criteria for the primary efficacy analysis. The primary end point of ORR by independent review was 9.3% (95% CI, 6.1% to 13.4%; all partial responses [PRs]), the stable disease (SD) rate was 46.5%, and clinical benefit rate (complete response + PR + SD > or = 6 months) was 17.1%. The investigator-reported ORR was 14.1% (95% CI, 10.2% to 18.9%). Median duration of response was 4.1 months, and progression-free survival was 2.6 months. Median overall survival was 10.4 months. The most common treatment-related grade 3 or 4 toxicities were neutropenia (54%; febrile neutropenia, 5.5%), leukopenia (14%), and asthenia/fatigue (10%; no grade 4); grade 3 neuropathy occurred in 6.9% of patients (no grade 4).


CONCLUSIONS
Eribulin demonstrated antitumor activity in extensively pretreated patients who had previously received an anthracycline, taxane, and capecitabine, with a manageable tolerability profile.
Cortes
Javier
J
Vall d'Hebron University Hospital, Barcelona, Spain. jacortes@vhebron.net
Vahdat
Linda
L
Blum
Joanne L
JL
Twelves
Chris
C
Campone
Mario
M
Roché
Henri
H
Bachelot
Thomas
T
Awada
Ahmad
A
Paridaens
Robert
R
Goncalves
Anthony
A
Shuster
Dale E
DE
Wanders
Jantien
J
Fang
Fang
F
Gurnani
Renuka
R
Richmond
Elaine
E
Cole
Patricia E
PE
Ashworth
Simon
S
Allison
Mary Ann
MA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D004988:Ethers, Cyclic; D005260:Female; D005663:Furans / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007659:Ketones / Q000009:adverse effects / Q000627:therapeutic use*; D018942:Macrolides; D008875:Middle Aged; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D019233:Retreatment; D000095662:Polyether Polyketides
D000970:Antineoplastic Agents; D004988:Ethers, Cyclic; D005663:Furans; D007659:Ketones; D018942:Macrolides; C070519:halichondrin B; D000095662:Polyether Polyketides; C490954:eribulin