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Abstract
Introduction
What is a Herceptin (Trastuzumab) ?
Herceptin (Trastuzumab) is an monoclonal antibody ,it is an example of targeted therapy an agent that is directed against a specific change in the cancer cell. Herceptin is approved for the adjuvant treatment of HER2-overexpressing, node-positive or node-negative (ER/PR-negative or with one high-risk feature) breast cancer.
__________________________
Methods
Results
Results Results
Conclusion The combination of Herceptin and chemotherapy decreased the death rate by 23 percent compared with chemotherapy alone. After a median follow-up period of 29 months, women treated with a combination of either Herceptin plus doxorubicin (or epirubicin) and cyclophosphamide (AC therapy), or Herceptin plus paclitaxel (Taxol) survived on average more than five months longer than those treated with the chemotherapy drugs alone (25.4 months vs. 20.3 months). Quality-of-Life Increases With Herceptin Use. Cardiac toxicity in the trial was 4.1 percent for those taking trastuzumab vs. 0.8 percent for those on standard chemotherapy The most common adverse reactions in patients receiving Herceptin are fever, nausea, vomiting, infusion reactions, diarrhea, infections, increased cough, headache, fatigue, dyspnea, rash, neutropenia, anemia, and myalgia Adverse reactions requiring interruption or discontinuation of Herceptin treatment include CHF, significant decline in left ventricular cardiac function, severe infusion reactions, and pulmonary toxicity 2 years herceptin administration showed no better results in OS versa 1 year herceptin administration.
Corresponding author and co-authors;
Gani Oruqaj; [email protected], mob; +377 44 23 77 42
Learta Pervizaj ; [email protected],
Lavdim Ibrahimi; [email protected]
Fig.no.1
Normal HER2 expression
HER2 amplification leads to HER2 overexpression
HER2 overexpression leads totumour proliferation
Treatment with Herceptin
r
Extracellular targetingHerceptin , Omnitarg,
cetuximabSignal
transductionto nucleus
Intracellular targeting
TarcevaT, gefitinib
Nuclear targetingantisense
oligonucleotides, ribozymes
Gene activation CELLDIVISION HER2/neu (also known as
ErbB-2, ERBB2) stands for "Human Epidermal growth factor Receptor 2" and is a protein giving higher aggressiveness in breast cancers. It is a member of the ErbB protein family, more commonly known as the epidermal growth factor receptor family. HER2/neu has also been designated as CD340 (cluster of differentiation 340) and p185.
An increased amount of HER2 is a marker for a very aggressive form of breast cancer. Approximately 30 percent of all breast cancers overexpress HER2.
The oncogene neu is so-named because it was derived from a cell line in rat. HER2 is named because it has similar structure to human epidermal growth factor receptor, or HER1. ErbB2 was named for its similarity to ErbB (avian erythroblastosis oncogene B), the oncogene later found to code for EGFR
Targeting the HER receptor
1. Extracellular targeting
2. Intracellular targeting
• Aim of research; • Trastuzumab q3w after standard adjuvant therapy• 1 vs 2 years of treatment• Adverse side events that often encounter during treatment• Crossover permitted after 1st interim efficacy analysis• Trial ;medical records of patients treated at the Cancer Clinic-
ONKOMED
IHC 3+ or FISH+ Node-positiveand high-risknode-negative EBC
Observation
1-year trastuzumab
2-year trastuzumab
8 mg/kg loading dose 6 mg/kg
q3w
Surgery + standard
predefined (neo)adjuvant
CT + RT
Trial design
AC, doxorubicin 60 mg/m2 or epirubicin 75 mg/m2 and cyclophosphamide 600 mg/m2
HER2, human epidermal growth factor receptor 2; IHC, immunohistochemistry, MBC;metastatic breast cancer
HER2-positive MBC (IHC 3 + or 2+)No prior chemotherapy for MBC
AC q3w x 6 cycles(n=138)
AC q3w x 6 cycles + trastuzumab 4 mg/kg loading, then 2 mg/kg qw until disease progression (n=143)
Paclitaxel 175 mg/m2
q3w x 6 cycles (n=96)
Paclitaxel 175 mg/m2 q3w x 6 cycles + trastuzumab 4 mg/kg loading, then 2 mg/kg qw until disease progression (n=92)
Prior adjuvant anthracyclines
(n 42)
No prior anthracyclines
(n 42)
-OS, overall survival
Probability of survival
17.9 24.8+40%
Trastuzumab + paclitaxel Paclitaxel
05 1
015
20 2
5
30
35
40
45
6.9 months
1.0
0.6
0.8
0.4
0.2
0.0
Trial : OS (IHC 3+ taxane subgroup)
-Patients progressing on docetaxel alone could cross over to receive trastuzumab-FISH, fluorescence in situ hybridisation; -LVEF, left ventricular ejection fraction-Patients show a better outcome in overall survival rate in the regimen docetaxel + trastuzumab ,8.5 months compared to paclitaxel + trastuzumab, 6.9 months
HER2-positive MBC (IHC 3+ and / or FISH+)No prior chemotherapy for MBCBaseline LVEF >50%
Docetaxel 100 mg/m2
q3w x 6 cycles( n 42)
Docetaxel 100 mg/m2
q3w x 6 cycles +trastuzumab 4 mg/kg loading, then 2 mg/kg qw until disease progression( n 42)
•Twice as many patients receiving trastuzumab survived 3 years (33% vs 16%)
Trastuzumab + docetaxel (n=92)Docetaxel alone (n=94)
Patients alive (%)
22.7 31.20
20
40
60
80
100
0 5 10 15 20 25 30 35 5040 45
+37%Time (months)8.5 months
OS (IHC 3+ / FISH+)
aBased on pretreatment blood counts only SAE, serious adverse event; H, trastuzumab; Diff, difference
SAE, %
Fever
Heart failure
Leucopeniaa
Febrile neutropenia
Alopecia
Alone(n=95)
1
1
5
-
26
H(n=91)
2
2
6
-
26
Diff
1
1
1
0
Alone(n=94)
1
0
15
17
6
H (n=92)
1
1
20
23
10
Diff
0
1
5
6
4
Paclitaxel Docetaxel
Effect of adding trastuzumab to chemotherapy: SAEs
BREAST CANCER -HERCEPTIN IMPACT AND SUCCESS IN PATIENTS WITH AGGRESSIVE BREAST CANCER AND HER 2+ PROVED BY IHC OR FISH
Gani Oruqaj, Learta Pervizaj, Lavdim Ibrahimi Armend Spahiu, MD, internist and medical oncologist
KOSOVO, University of Prishtina-Prishtina, Medical Faculty, Cancer Care Clinic –ONKO-MED-Prizren,Kosovo
FISH
Patient tumour sample
Herceptin®
therapy
+–2+
3+
1+0
+–
FISH
IHC
Herceptin®
therapy
Herceptin®
therapy
Interceptors of HER signalling
HER2 testing algorithm
Methods and Material used in
the trial to find out the HER 2
positivity in women with MBC.
IHC and FISH confirm
Patients alive (%)
22.7 31.20
20
40
60
80
100
0 5 10 15 20 25 30 35 5040 45
+37%
8.5 months
1 year Trastuzumab trial2 years Trastuzumab trial
Acknowledgements ; Cancer Care Clinic –ONKO-MED, Prizren-Kosovo ,Armend Spahiu , MD, medical oncologist,
ONKO-MED
