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1. The Magnitude of benefit. By Osama Elzaafarany Assistant
Lecturer of Clinical Oncology Medical Research Institute - Alex.
University Adding Trastuzumab to adjuvant chemotherapy in Breast
cancer patients
2. Hey Doctor, Is it worthy to receive Herceptin?
3. Trastuzumab: Humanized Monoclonal antibody, against human
epidermal growth factor receptor 2 (HER2). Mediates
antibody-dependent cellular cytotoxicity against cells that
over-express HER2, and lacks effect on cells not over-expressing
HER2. Half-life: 6 days.Dosing: 4 mg/kg IV over 90 minutes, THEN 2
mg/kg IV over 30 minutes qWeek during chemotherapy for the first 12
weeks (paclitaxel or docetaxel) or 18 weeks
(docetaxel/carboplatin). Weekly
4. Evidence Based Medicine +ve trials -ve trial NSABP-B31 /
NCCTG BCRIG 006 FNCLCC-PACS-04 Chemo alone VS Chemo +
Herceptin
5. NSABP-B31: (NEGM, 2005)
6. +ve LNs High-risk ve LNs
7. The B-31 and NCCTG trials have been jointly analyzed using:
merged control arms (chemo alone) VS merged arms using concurrent
Taxol + Herceptin. There were 4045 patients included in the joint
analysis. Median follow-up of 3.9 years.
8. Addition of adjuvant Trastuzumab to chemotherapy has both
significant DFS and OS benefit compared with chemotherapy alone.
48% reduction in the risk of recurrence (P > 0.001). 39%
reduction in risk of death ( P = 0.001).
9. Kaplan-Meier estimates of (A) event-free survival and (B)
overall survival. Disease events include local, regional, or
distant recurrence; contralateral breast cancer; second primary
cancers; or death as a result of any cause. Overall survival is
measured from the time of study enrollment to last contact or
death. AC,doxorubicin and cyclophosphamide; H, trastuzumab; T,
paclitaxel.
10. Absolute differences in DFS increased by number of LNs
metas; it was most pronounced for patients with 10 +ve LNs, who had
an unprecedented 27% absolute improvement.
11. Cardiac safety: The rate of symptomatic heart failure was:
0.5% with chemotherapy alone. 2.0% with AC followed by paclitaxel
and trastuzumab. 86% of patients in the Trastuzumab arms had either
complete or partial resolution of the cardiac event in follow-up.
Risk factors for cardiac events: Patients 60 years old (P=0.003).
Patients with prior or current use of antihypertensive medication
(P= 0.005). Patients with LVEF near the LLN at registration (P
=0.033).
12. TC + Herceptin AC-T + Herceptin AC-T 81 %84 %75 %5-ys DFS
91 %92 %87 %OS The addition of 1 year of adjuvant Trastuzumab
significantly improved disease-free and overall survival among
women with HER2-positive breast cancer.
13. The survival benefit and the risk of congestive heart
failure (CHF) associated with adjuvant trastuzumab plus
chemotherapy can be estimated as follows: Benefit VS Side effects
For patients with high risk HER2-positive breast cancer,
trastuzumab is associated with an absolute risk reduction (ARR) of
death of 13.3 % (mortality rate=36.7 VS 50 % in controls). The
number of patients needed to treat (NNT) to save one life is 8. For
patients with low risk disease, the ARR is 3.3 % (10 VS 6.7 %,
respectively). The NNT is 31. For patients at high risk for CHF
prior to trastuzumab treatment, the absolute risk increase (ARI) of
CHF associated with trastuzumab is 21 % (26 VS 5 % in controls).
The number of patients needed to harm (NNH) is 5. For patients at
low risk for CHF, the ARI is 2.1 % (2.6 VS 0.5 %, respectively).
The NNH in this group is 48.
14. The recent treatment guideline recommend adjuvant
chemotherapy plus HER2-directed treatment for: All women with
HER2-positive, node-positive breast cancer. Women with
HER2-positive, node-negative tumors >1 cm in size. Improvement
in disease-free survival (DFS, hazard ratio [HR] for recurrence
0.60, 95% CI 0.50-0.71), regardless of trastuzumab treatment
duration or the administration schedule (ie, concurrent with
chemotherapy or sequentially following chemotherapy). Improvement
in overall survival (OS, HR for mortality 0.66, 95% CI 0.57-0.77)
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