Both Halaven and Exjeva are new drugs that were recently approved.
HALAVEN( eribubilin) is indicated for the treatment of patients with metastatic breast cancer who have previously received at least two chemotherapeutic regimens for the treatment of metastatic disease. Prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting.
This was based on an open-label, randomized, multicenter trial of 762 patients with metastatic breast cancer who received at least two chemotherapeutic regimens for the treatment of metastatic disease and experienced disease progression within 6 months of their last chemotherapeutic regimen, EMBRACE study. A statistically significant improvement in overall survival was observed in patients randomized to the Halaven arm compared to the control. An updated, unplanned survival analysis, conducted when 77% of events had been observed, was consistent with the primary analysis. In patients randomized to Halaven, the objective response rate by the RECIST criteria was 11% (95% CI: 8.6%, 14.3%) and the median response duration was 4.2 months (95% CI: 3.8, 5.0 months). The difference between overall survival in the 2 treatment groups was statistically significant; median overall survival was 13.1 months with eribulin and 10.6 months with TPC (hazard ratio, 0.81; P = .041).
This was significant but not very pronounced. The magnitude of the improvement is similar to what has been reported for docetaxel vs mitomycin plus vinblastine (31%), and for capecitabine plus docetaxel vs docetaxel alone (26%). It does not mean that Havalen is better than all other chemo choices, which remains for subsequent studies to determine, only that it is somewhat better than “any single-agent treatment (chemotherapy, hormonal or biological) or radiotherapy or symptomatic therapy alone”. Many physicians chose to use vinorelbine, gemcitabine, or capecitabine in the control arm; none chose supportive care and none used combinations.There was a prior phase II study that included patient pre-treated with anthracyclines, taxanes or capecitibine.
Although approved after anthracycline therpay, a pattern of care study in 2014 showed that in practice the drug is used irrespective of prior anthracycline used. There was no significant difference detected for prior anthracycline use impacting the number of eribulin administrations or days of therapy.
There are also two studies supporting its use in first line, withouu prior treatment. At SABCS 2012, the results of a phase clinical trial (Study 206, NCT01268150) of eribulin monotherapy as first-line treatment for locally recurrent or metastatic HER2 negative breast cancer were presented. Efficacy and safety were evaluated. Of 56 enrolled patients, 54 had at least 1 post-baseline assessment. ORR was 31% [complete response (CR) 0%, partial response (PR) 31%, stable disease (SD) 48%], and CBR was 48%. The median time to response (TTR), duration of response (DOR), and PFS were 1.4, 5.8, and 6.1 months, respectively. Treatment-related serious adverse events occurred in 5 patients (9%): neutropenia (4%), and febrile neutropenia (5%). At SABCS 2012, the results of a phase clinical trial (Study 208, NCT01269346) of eribulin plus trastuzumab as first-line combined therapy for locally recurrent or metastatic HER2-positive breast cancer were presented. Efficacy and safety were evaluated. 37 of 52 planned patients have been treated. The ORR was 60% [CR 5%, PR 54%, SD 30%, progressive disease (PD%], and CBR was 70%. Treatment-related serious adverse events occurred in 4 patients (11%): neutropenia (8%), and febrile neutropenia (6%).
Xgeva(denosumab) is indicated for the prevention of skeletal-related events in patients with bone metastases from solid tumors. In the pivotal study, Denosumab was superior to zoledronic acid in delaying or preventing SREs in patients with breast cancer metastatic to bone and was generally well tolerated. With the convenience of a subcutaneous injection and no requirement for renal monitoring, denosumab represents a potential treatment option for patients with bone metastases. It is not approved for myeloma but there are studies supporting it for that diagnosis.
Halaven, Prescribing Information: http://www.eisai.com/pdf_files/Halaven_PI.pdf, 2013
35th Annual San Antonio Breast Cancer Symposium (SABCS): Abstract S6-6. Presented December 7, 2012
nccn, Breast Cancer 2013
Alison T. Stopeck, et al, Denosumab Compared With Zoledronic Acid for the Treatment of Bone Metastases in Patients With Advanced Breast Cancer: A Randomized, Double-Blind Study JCO November 8, 2010 JCO.2010.29.7101
Monica N. Fornier Denosumab: Second Chapter in Controlling Bone Metastases or a New Book? JCO Dec 10, 2010:5127-5131
David H. Henry, Luis Costa, Francois Goldwasser, Vera Hirsh, Vania Hungria, Jana Prausova, Giorgio Vittorio Scagliotti, Harm Sleeboom, Andrew Spencer, Saroj Vadhan-Raj, Roger von Moos, Wolfgang Willenbacher, Penella J. Woll, Jianming Wang, Qi Jiang, Susie Jun, Roger Dansey and Howard Yeh, Randomized, Double-Blind Study of Denosumab Versus Zoledronic Acid in the Treatment of Bone Metastases in Patients With Advanced Cancer (Excluding Breast and Prostate Cancer) or Multiple Myeloma. JCO March 20, 2011 vol. 29 no. 9 1125-1132
Ali McBride, Claudio Faria, Xuan Li, Annette Powers; University of Arizona Cancer Center, Tucson, AZ; Eisai Inc., Woodcliff Lake, NJ
Eribulin treatment patterns in patients with and without prior anthracycline use. J Clin Oncol 32, 2014 (suppl 30; abstr 292)
Vahdat LT, Schwartzberg L, Gluck S, Rege J, OShaughnessy J. Results of a phase 2, multicenter, single-arm study of eribulin mesylate as first-line therapy for locally recurrent or metastatic HER2-negative breast cancer. Cancer Res 2012; (Suppl.): Abstr P1-12-02.
Vahdat LT, Schwartzberg L, Wilks S, Rege J, Liao J, Cox D, OShaughnessy J. Eribulin mesylate + trastuzumab as first-line therapy for locally recurrent or metastatic HER2-positive breast cancer. results from a phase 2, multicenter, single-arm study. Cancer Res 2012; (Suppl.): Abstr P5-20-04.
Xgeva, Prescribing Information
Read the Layperson version here.