Optimal salvage treatment for HER2-positive breast cancer after trastuzumab and T-DM1 failure still remains to be established. We would like to investigate the efficacy and safety of combination chemotherapy of eribulin and trastuzumab as salvage treatment for HER2-Positive breast cancer after exposure to trastuzumab and T-DM1
HER2-targeted therapy is the mainstay therapeutic option for the treatment of HER2 positive breast cancer patients. Even after progression on HER2-targeted therapy, HER2 remains an effective therapeutic target. In a phase III randomized clinical trial, Lapatinib plus capecitabine showed superior outcome compared to capecitabine alone in HER2 positive breast cancer patients who has progressed after trastuzumab-based therapy Moreover, ado-trastuzumab emtansine (T-DM1) showed improved progression free survival (PFS) and overall survival (OS) in HER2-positive advanced breast cancer patients previously treated with trastuzumab and a taxane. Not only switching to a different HER2-targeted agent, but rechallenge of trastuzumab has also shown efficacy in trastuzumab failed HER2-positive breast cancer patients. In HER2-positive breast cancer patients who failed trastuzumab and lapatinib, rechallenge of trastuzumab in combination with conventional chemotherapy showed response rate of 31%, PFS of 4.9 months, and OS of 19.4 months. Eribulin mesylate is a non-taxane inhibitor of microtubule which shows efficacy in HER2-positive breast cancer. The efficacy of eribulin and trastuzumab combination chemotherapy as first line palliative chemotherapy in HER2-positive breast cancer was identified in a phase II trial. Eribulin plus trastuzumab was an effective regimen which showed response rate of 71.2% and PFS of 11.6 months. Currently, the first line regimen for HER2-positive metastatic breast cancer is combination therapy of pertuzumab, trastuzumab, and docetaxel as a result of the CELOPARTRA trial . After failure on pertuzumab and trastuzumab based combination chemotherapy, T-DM1 is frequently used as a 2nd line therapy. Optimal salvage treatment for HER2-positive breast cancer after trastuzumab and T-DM1 failure still remains to be established. We would like to investigate the efficacy and safety of combination chemotherapy of eribulin and trastuzumab as salvage treatment for HER2-Positive breast cancer after exposure to trastuzumab and T-DM1.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
180
* Patients will receive eribulin mesylate 1.4 mg/m2 administered I.V. with infusion over 2 to 5 minutes on days 1 and 8 of each 21-day cycle and SB3 8 mg/kg I.V. over 90 minutes on day 1 of cycle 1 . Thereafter, SB3 6 mg/kg will be infused over 30 minutes on day 1 of each subsequent 21-day cycle until progression or unacceptable toxicity. * Dose reductions for eribulin, but not for SB3, is permitted. * Two dose reductions (1.1, 0.7 mg/m2) are allowed for eribulin before consideration of study treatment discontinuation. Eribulin could be continued as monotherapy if trastuzumab-similar was discontinued, and vice-versa.
* Patients will receive eribulin mesylate 1.4 mg/m2 administered I.V. with infusion over 2 to 5 minutes on days 1 and 8 of each 21-day cycle until progression or unacceptable toxicity. * Two dose reductions (1.1, 0.7 mg/m2) are allowed before consideration of study treatment discontinuation.
Seoul National University Hospital
Seoul, South Korea
RECRUITINGPrimary Efficacy Endpoint(PFS)
PFS is defined as the time from randomization to first documented disease progression as determined by the investigator using RECIST 1.1 or death from any cause, whichever occurs earlier.
Time frame: First day of study treatment to the date of disease progression or death due to any cause, whichever came first, assessed up to 2 years
Objective response rate (ORR)
Objective response, defined as a CR or PR, will be determined by investigator tumor assessment using RECIST 1.1. Patients without a post-baseline tumor assessment will be considered non-responders.
Time frame: Enrollment to end of treatment up to 2 years
Duration of objective response (DOR)
DOR is defined as the time from first occurrence of a documented objective response (PR or CR) to disease progression, as determined by investigator tumor assessment using RECIST 1.1, or death from any cause, whichever occurs first
Time frame: Enrollment to end of treatment up to 2 years
Clinical benefit rate (CBR)
Clinical benefit rate, defined as having received CR or PR of any duration or stable disease (SD) ≥ 4 months per RECIST v1.1. Patients without a post-baseline tumor assessment will be considered non-responders
Time frame: Enrollment to end of treatment up to 2 years
Overall survival (OS)
OS is defined as the time from randomization to death from any cause. Patients who are alive as of the data cut-off date of the analysis will be censored at the last known date they were alive
Time frame: First day of study treatment to the date of death due to any cause, assessed up to 2 years
Safety profile (Treatment-related adverse events as assessed by CTCAE v4.0)
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Number of participants with treatment-related adverse events will be assessed
Time frame: First day of study treatment to end of treatment, assessed up to 2 years