Phase II study of eribulin mesylate, a halichondrin B analog, in patients with metastatic breast cancer previously treated with an anthracycline and a taxane.
OBJECTIVE
Eribulin mesylate (E7389), a nontaxane microtubule dynamics inhibitor, is a structurally simplified, synthetic analog of the marine natural product halichondrin B. This open-label, single-arm, phase II study evaluated efficacy and tolerability of eribulin in heavily pretreated patients with metastatic breast cancer (MBC).


METHODS
MBC patients who were previously treated with an anthracycline and a taxane received eribulin mesylate (1.4 mg/m(2)) as a 2- to 5-minute intravenous (IV) infusion on days 1, 8, and 15 of a 28-day cycle. Because of neutropenia (at day 15), an alternative regimen of eribulin on days 1 and 8 of a 21-day cycle was administered. The primary end point was overall response rate.


RESULTS
Of the 103 patients treated, the median number of prior chemotherapy regimens was four (range, one to 11 regimens). In the per-protocol population (n = 87), eribulin achieved an independently reviewed objective response rate (all partial responses [PRs]) of 11.5% (95% CI, 5.7 to 20.1) and a clinical benefit rate (PR plus stable disease > or = 6 months) of 17.2% (95% CI, 10.0 to 26.8). The median duration of response was 171 days (5.6 months; range, 44 to 363 days), the median progression-free survival was 79 days (2.6 months; range, 1 to 453 days), and the median overall survival was 275 days (9.0 months; range, 15 to 826 days). The most common drug-related grades 3 to 4 toxicities were as follows: neutropenia, 64%; leukopenia, 18%; fatigue, 5%; peripheral neuropathy, 5%; and febrile neutropenia, 4%.


CONCLUSIONS
Eribulin demonstrated activity with manageable tolerability (including infrequent grade 3 and no grade 4 neuropathy) in heavily pretreated patients with MBC when dosed as a short IV infusion on days 1 and 8 of a 21-day cycle.
Vahdat
Linda T
LT
Weill Medical College of Cornell University, Division of Hematology/Oncology, New York, NY 10021, USA. ltv2001@med.cornell.edu
Pruitt
Brian
B
Fabian
Carol J
CJ
Rivera
Ragene R
RR
Smith
David A
DA
Tan-Chiu
Elizabeth
E
Wright
Jonathan
J
Tan
Antoinette R
AR
Dacosta
Noshir A
NA
Chuang
Ellen
E
Smith
John
J
O'Shaughnessy
Joyce
J
Shuster
Dale E
DE
Meneses
Nicole L
NL
Chandrawansa
Kumari
K
Fang
Fang
F
Cole
Patricia E
PE
Ashworth
Simon
S
Blum
Joanne L
JL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018943:Anthracyclines / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy*; D001952:Bridged-Ring Compounds / Q000627:therapeutic use; D004988:Ethers, Cyclic / Q000627:therapeutic use; D005260:Female; D005663:Furans / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D006801:Humans; D007659:Ketones / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D018942:Macrolides; D008870:Microtubules / Q000187:drug effects; D008875:Middle Aged; D009362:Neoplasm Metastasis; D043823:Taxoids / Q000627:therapeutic use; D016896:Treatment Outcome; D000095662:Polyether Polyketides
D018943:Anthracyclines; D000970:Antineoplastic Agents; D001952:Bridged-Ring Compounds; D004988:Ethers, Cyclic; D005663:Furans; D007659:Ketones; D018942:Macrolides; D043823:Taxoids; C080625:taxane; C070519:halichondrin B; D000095662:Polyether Polyketides; C490954:eribulin