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Journal club presentation

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sahar ali

on 1 February 2014

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Transcript of Journal club presentation

Journal club presentation
Clinical Question
amplification of human epidermal growth factor receptor 2 (HER2) occurs in approximately 20% of breast cancers and is associated with shortened survival.
Trastuzumab Emtansine for HER2-positive Advanced Breast Cancer
N Engl J Med. 2013 Jun 20;368(25):2442.
Dr. Dalal M. Bin-Zouman
Sahar A. Alkhalifah , PharmD. Candidate 2013
Princess Norh Bint Abullrahman University
Oncology Rotation
HER2-positive advanced breast cancer
When combined with first-line chemotherapy, trastuzumab increases the time to progression and overall survival among patients with metastatic disease.
Trastuzumab Emtansin
Trastuzumab emtansine (T-DM1) is an antibody–drug conjugate that incorporates the HER2-targeted antitumor properties of trastuzumab with the cytotoxic activity of the microtubule-inhibitory agent .
It allows intracellular drug delivery specifically to HER2-overexpressing cells, thereby improving the therapeutic index and minimizing exposure of normal tissue.
Among patients with advanced HER2-positive breast cancer previously treated with trastuzumab and a taxane, does trastuzumab-emtansine prolong PFS and OS when compared to lapatanib+capecitabine?
study design
Randomization :
Study procedures
Patients in the control group self-administered oral lapatinib at a dose of 1250 mg daily + oral capecitabine at a dose of 1000 mg per square meter of body-surface area every 12 hourson days 1 through 14 of each 21-day treatment cycle and recorded their doses in a patient diary.
statistical analysis
Setting: 213 centers in 26 countries
Multicenter, randomized, open-label trial

991 Women with HER2+, unresectable, locally advanced or metastatic breast cancer who were previously treated with a taxane and trastuzumab

496 patient on Lapatinib and capecitabine
495 patient on T-DM1
study End points
Patients were randomly assigned in a 1:1 ratio to T-DM1 or lapatinib plus capecitabine with the use of a hierarchical, dynamic randomization scheme through an interactive voice-response system .
Prior treatment with T-DM1, lapatinib, or capecitabine
Peripheral neuropathy >grade 3
Symptomatic CNS metastases or treatment of CNS disease within prior 2 months
Serious cardiac arrhythmia
ACS in prior 6 months
Progression of unresectable, locally-advanced or metastatic HER2+ breast cancer
Previous treatment with a taxane and trastuzumab
LVEF >50%
ECOG 0-1
Inclusion Criteria
Exclusion Criteria
Patients randomly assigned to T-DM1 received 3.6 mg per kilogram of body weight intravenously every 21 days.
Tumor assessments were performed by the independent review committee at baseline and every 6 weeks E
The left ventricular ejection fraction was measured by means of echocardiography (the preferred method) or MUGA scanning at baseline, week 6, week 12, and every 12 weeks
Progression was assessed according to modified Response Evaluation Criteria in Solid Tumors (RECIST).
Adverse events were monitored continuously and graded according to the CTCAET
baseline characteristic of the patients
Primary Efficacy endpoint
Progression-free survival
Secondary Efficacy End Points
Treatment Exposure
Safety endpoint
Death in the study
2nd Interim
1st Interim
total = 2
Jadad scale

In February 2013, the FDA approved T-DM1 for use in patients with metastatic, HER2-positive breast cancer and previous treatment with trastuzumab and a taxane, but no major guidelines have been released to reflect the results of this trial.


F. Hoffman-La Roche/Genentech, the manufacturers of T-DM1 under the trade name Kadcyla
journal critique
Appropriate study design
Appropriate sample size
Well distributed baseline characteristics
First, the study, though randomized, is not “blinded”
how T-DMI will be used in the context of expanding treatment options for women with Her2+ breast cancer.
T-DM1 significantly prolonged progression-free and overall survival with less toxicity than lapatinib plus capecitabine in patients with HER2-positive advanced breast cancer previously treated with trastuzumab and a taxane.
Thank you
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