Log in to post a reply
Apr 10, 2012 07:35AM
Alaska Angel... YOU KNOW VERY WELL THAT THERE IS EXACTLY ONE STUDY THAT IS SEEKING TO DETERMINE THE EFFECTIVENESS OF HERCEPTIN MONOTHERAPY AND THAT INVOLVES A POPULATION OF HER2+ PATIENTS OVER THE AGE OF 70. AND YOU ALSO KNOW THAT IT WOULD BE ETHICALLY CHALLENGING TO SUGGEST DOING JUST HERCEPTIN WITH YOUNGER PATIENTS. YOU ALSO KNOW THAT BASED ON THE INFORMATION THAT DANCETRANCER HAS BEEN KIND ENOUGH TO PROVIDE HERE ON THIS THREAD THAT MANY DOCTORS ARE IN A QUANDRAY AS TO WHAT KIND OF THERAPY TO SUGGEST FOR THE SMALLEST OF SMALL HER2+ TUMORS BECAUSE THERE ARE NO FORTHCOMING TRIALS.
HERE ARE THE CURRENT CLINICAL TRIALS THAT ARE UNDERWAY INVOLVING CHEMO AND HERCEPTIN:
Herceptin trials in early breast cancer
This page tells you about research into using trastuzumab (Herceptin) for early breast cancer to try to stop the cancer from coming back. There is information about
What Herceptin is
Trastuzumab (Herceptin) is a biological cancer treatment. It is a monoclonal antibody that attaches to the HER2 protein found on the cells of some breast cancers. Cancers that are HER2 positive tend to have a worse outlook than cancers that are HER2 negative. If the cells of your cancer aren't HER2 positive, Herceptin won't help to treat it. Between 20 to 25 out of every 100 early breast cancers (20 to 25%) have the HER2 protein on their cells.
Back to top
Trial results for Herceptin in early breast cancer
3 large trials looked into using Herceptin to treat HER2 positive early breast cancer. They aimed to try to stop the cancer from coming back. Two of the trials were American and one is a very large European and worldwide trial called HERA. The trials looked at giving Herceptin as well as chemotherapy to women after surgery to remove their breast cancer. The researchers wanted to see whether the combined treatment could reduce the risk of breast cancer coming back even more than chemotherapy on its own. This type of treatment is called adjuvant therapy.
All the trials were for women who had breast cancer that tested positive for HER2. And most of them had cancer spread to their lymph nodes. This meant that the women had a high risk of their breast cancer coming back. In the trials the women either had Herceptin after their chemotherapy or at the same time. The trials showed that the cancer came back in about half as many women when compared to chemotherapy given without Herceptin. But we'll have to wait a few more years yet to get longer term results for all the women who took part.
A smaller fourth trial gave a short course of trastuzumab to women with lymph node-positive tumours or tumours bigger than 2 cm. The women had nine weekly infusions of trastuzumab with their chemotherapy. The risk of the cancer coming back and the risk of dying was significantly reduced in the women who had Herceptin.
It is important to know that Herceptin can cause heart problems in some women. This is more likely if you have had chemotherapy with a drug that also causes heart problems. Doxorubicin (adriamycin) is one such drug and it was used with Herceptin in the early breast cancer trials because it is particularly good at preventing breast cancer recurrence.
There are clinical trials looking at treating early breast cancer with Herceptin. There is a phase 3 trial called EPHOS B looking at the effect of having trastuzumab (Herceptin) or lapatinib before surgery. Research has shown that having Herceptin after surgery lowers the risk of the cancer coming back in people with HER2 positive breast cancer. The researchers want to find out if having drugs that work by blocking HER2 protein before surgery may lower the risk more.
Another phase 3 trial called SOLD is looking at having Herceptin with chemotherapy for early breast cancer. The aim of this trial is to compare having Herceptin with chemotherapy to the same treatment followed by continued Herceptin for one year.
There is another phase 3 trial called PERSEPHONE. This trial is comparing 6 months and 12 months of trastuzumab for early breast cancer. The aim of this trial is to find out if 6 months of treatment works as well as 12 months. As Herceptin can cause heart problems in some women, the researchers also want to find out if having treatment for a shorter time can help lower the risk of damage to the heart.
APHINITY is a phase 3 trial looking at Herceptin and pertuzumab for HER2 positive breast cancer. Pertuzumab is another monoclonal antibody that also targets the HER2 protein. The researchers want to find out if giving pertuzumab and Herceptin is better than Herceptin alone for people who have had surgery for HER2 positive breast cancer.
Back to top
What we don't know yet
Although Herceptin has been shown to reduce the chance of cancer coming back in women with HER 2 positive breast cancer, there are still some questions about how best to use Herceptin, such as
- When is the best time to have Herceptin
- How long to prescribe it for
- Whether any long term risks of this treatment could outweigh the benefits for some women
- Whether the treatment just delays the breast cancer coming back rather than preventing it altogether
To answer these questions, research into Herceptin for early breast cancer is continuing. For now, the National Institute for Health and Clinical Excellence (NICE) have said that doctors should give it 3 weekly for a year (after surgery, chemotherapy and radiotherapy has finished). They may revise this in future depending on new research results.
Back to top
More information about Herceptin for early breast cancer
There is detailed information about the NICE guidance on Herceptin for early breast cancer in the biological therapy for early breast cancer section.
You can find out more about Herceptin trials for breast cancer on our clinical trials database. Choose 'breast cancer' from the dropdown menu of cancer types and type 'trastuzumab' into the text box. If you want to see all the trials, tick the boxes for closed trials and trial results.
AND HERE'S THE STUDY FOR THE OVER 70 POPULATION USING HERCEPTIN AS MONOTHERAPY:
Evaluation of Trastuzumab Without Chemotherapy as a Post-operative Adjuvant Therapy in HER2-positive Elderly Breast Cancer Patients: Randomized Controlled Trial [RESPECT (N-SAS BC07)]†
- Masataka Sawaki1,*,
- Nahomi Tokudome2,
- Toshiro Mizuno3,
- Takahiro Nakayama4,
- Naruto Taira5,
- Hiroko Bando6,
- Shigeru Murakami7,
- Yutaka Yamamoto8,
- Masahiro Kashiwaba9,
- Hiroji Iwata10,
- Yukari Uemura11 and
- Yasuo Ohashi11
+ Author Affiliations
- 1Department of Clinical Oncology and Chemotherapy, Nagoya University Graduate School of Medicine, Nagoya
- 2Department of Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo
- 3Department of Medical Oncology, Mie University Hospital, Tsu
- 4Department of Breast and Endocrine Surgery, Osaka University Hospital, Osaka
- 5Department of Breast and Endocrine Surgery, Okayama University Hospital, Okayama
- 6Department of Breast and Endocrine Surgery, Graduate School of Comprehensive Human Science, University of Tsukuba, Tsukuba
- 7Department of Breast Surgery, Hiroshima City Asa Hospital, Hiroshima
- 8Department of Breast and Endocrine Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto
- 9Department of Surgery, Iwate Medical University, Morioka
- 10Department of Breast Oncology, Aichi Cancer Center Hospital, Nagoya
- 11Department of Biostatistics, School of Public Health, University of Tokyo, Tokyo, Japan
- *↵For reprints and all correspondence: Masataka Sawaki, Department of Clinical Oncology and Chemotherapy, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. E-mail: email@example.com
↵† An abstract was presented in part at 2010 Breast Cancer Symposium, Washington, DC, 1-3 October 2010.
- Received November 2, 2010.
- Accepted January 14, 2011.
Objective This trial is conducted to investigate the benefit of trastuzumab monotherapy compared with a combination therapy of trastuzumab and chemotherapy in women over 70 years with human epidermal growth factor receptor type-2-positive primary breast cancer.
Methods Inclusion criteria are the following: histologically diagnosed as invasive breast cancer and received curative operation for primary breast cancer; Stage I, IIA, IIB or IIIA/M0; and baseline left ventricular ejection fraction is ≥55%. Patients are randomized to receive either trastuzumab (8 mg/kg loading dose, 6 mg/kg every 3 weeks for 1 year) plus chemotherapy selected from regimens specified on the protocol or trastuzumab monotherapy. The primary endpoint is disease-free survival. Secondary endpoints are overall survival, relapse-free survival, safety, health-related quality of life, comprehensive geriatric assessment and cost effectiveness.
Results Patients recruitment has been commenced in October 2009. Enrollment of 300 patients is planned during the 4-year recruitment period.
Conclusions We hereby report the study concept.
Key wordsPrevious SectionNext Section
Trastuzumab with chemotherapy is the standard treatment as an adjuvant systemic therapy for human epidermal growth factor receptor type-2 (HER2)-positive primary breast cancer (1-4). Overexpression of HER2 has also been associated with potentially more aggressive tumors; therefore, trastuzumab is a key drug in the treatment of HER2-positive primary cancer. However, monotherapy of trastuzumab as an adjuvant treatment without concurrent or preceding chemotherapy is not conducted in clinical practice since its benefit has not been investigated as well as elderly patients (5). It has clinical significance to demonstrate the benefit of trastuzumab monotherapy without toxicity induced by chemotherapy, especially in elderly patients. Chemotherapy is not always a standard therapy in elderly patients based on the analysis of Early Breast Cancer Trialists' Collaborative Group (EBCTCG) because of limited data (6). Careful monitoring is necessary for elderly patients due to toxicity, cardiac toxicity associated with anthracycline-containing chemotherapy (7,8), increasing in acute myeloid leukemia (AML) after adjuvant chemotherapy (9).
This trial is conducted to investigate the clinical positioning between trastuzumab monotherapy (H group) and a combination therapy of trastuzumab and chemotherapy (H + CT group) based on a randomized controlled trial in women over 70 years with HER2-positive primary breast cancer. Previous SectionNext Section
DIGEST OF THE STUDY PROTOCOL
This study is conducted to investigate the clinical positioning between trastuzumab (Herceptin) monotherapy (H group) and a combination therapy of trastuzumab and chemotherapy (H + CT group) based on a randomized controlled trial in women over 70 years with HER2-positive primary breast cancer (Fig. 1). Our hypothesis includes the following two points:
View larger version:
Study schema. Evaluation of trastuzumab without chemotherapy as a post-operative adjuvant therapy in HER2-positive elderly breast cancer patients: randomized controlled trial [RESPECT (N-SAS BC07)].
HER2, human epidermal growth factor receptor type-2; IHC, immunohistochemistry; FISH, fluorescence in situ hybridization; PTX, paclitaxel; DTX, docetaxel; AC, doxorubicin and cyclophosphamide; EC, epirubicin and cyclophosphamide; CMF, cyclophosphamide, methotrexate and 5-fluorouracil.
This study is a multi-institutional prospective randomized controlled trial with 56 participating centers as of 31 August 2010.
This study was funded by Comprehensive Support Project for Oncology Research (CSPOR) of Public Health Research Foundation. All decisions concerning the planning, implementation and publication of this study were made by the executive committee of this study.
The primary endpoint is DFS. Secondary endpoints are overall survival, relapse-free survival, adverse events, HRQOL, comprehensive geriatric assessment and cost-effectiveness analysis.
(i) Histologically diagnosed as invasive breast cancer and received curative operation for primary breast cancer.
(ii) Stage I [tumor size (pT) ≥1 cm), IIA, IIB or IIIA/M0; female between 70 and 80 years old.
(iii) Primary cancer is HER2-positive (either 3+ overexpression or positive by fluorescence in situ hybridization).
(iv) Baseline left ventricular ejection fraction is ≥55% measured by echocardiography or multigated acquisition scan within 4 weeks before registration.
(v) Performance status (PS) 0-1.
(vi) Sufficient organ function meeting the following criteria within 4 weeks before registration:
(a) Leukocyte ≥2500 mm3
(b) Neutrophil ≥1500 mm3
(c) Platelet ≥100 000 mm3
(d) Serum total bilirubin ≤2.0× the upper limit of normal (ULN)
(e) Alanine aminotransferase (glutamic pyruvic transaminase) or aspartate aminotransferase (glutamic oxaloacetic transaminase) ≤2.5× ULN
(f) Serum creatinine ≤2.0× ULN
(g) Alkaline phosphatase ≤2.5× ULN
(vii) No previous endocrine therapy or chemotherapy for breast cancer.
(viii) Signed written informed consent.
(i) Active multiple primary cancer (synchronous multiple primary cancer and invasive cancer of other organs).
(ii) Post-operative histological axillary lymph node metastasis ≥4.
(iii) Axillary lymph node is not histologically evaluated.
(iv) Histologically confirmed positive margin in breast conservation surgery (evaluation of margin status is based on the policy of site).
(v) History of drug-related allergy which could hinder planned treatment.
(vi) Any history or complication of the following cardiac disorders.
(vii) History of congestive heart failure, cardiac infarction.
(viii) Complication requires treatment such as ischemic cardiac disorder, arrhythmia and valvular heart disease.
(ix) Poorly controlled hypertension (e.g. systolic arterial pressure ≥180 mmHg or diastolic blood pressure ≥100 mmHg).
(x) Poorly controlled diabetes.
(xi) Continuous visit to a medial institution is considered difficult due to deterioration of activity of daily living.
(xii) Difficult to participate in the trial because of psychiatric disorder or psychiatric symptoms.
(xiii) Ineligible to the trial based on the decision of an investigator.
The CSPOR Data Center will confirm patient eligibility, and treatment will be automatically assigned according to the assignment adjustment factors for eligible patients. The following five variables will be used as assignment adjustment factors: age (70-75/76-80), PS (0/1), hormone sensitivity, lymph node metastasis and hospital.
Combination Therapy of Trastuzumab and Chemotherapy Arm
The loading administration dose of trastuzumab is 8 mg/kg of body weight, and the maintenance dose is 6 mg/kg every 3 weeks for 1 year. Chemotherapy is selected from regimens specified on the protocol based on the decision of a physician or a patient.
(i) Paclitaxel (PTX) 80 mg/m2 weekly administered every week for 11 cycles.
(ii) Docetaxel (DTX) 75 mg/m2 every 3 weeks for four cycles.
(iii) Doxorubicin (A) 60 mg/m2 and cyclophosphamide (C) 600 mg/m2 every 3 weeks for four cycles.
(iv) Epirubicin (E) 90 mg/m2 and cyclophosphamide (C) 600 mg/m2 every 3 weeks for four cycles.
(v) Cyclophosphamide (C) 75-100 mg orally from days 1 to 14, methotrexate (M) 40 mg/m2 on days 1 and 8 intravenously, and 5-fluorouracil (F) 500-600 mg/m2 intravenously on days 1 and 8, every 4 weeks for six cycles.
Administration of trastuzumab initiates after completion of chemotherapy as a sequential combination. However, concomitant administration is allowed when combining trastuzumab with PTX, DTX and CMF.
If the hormone receptor is positive, hormone therapy is indicated. In the case of after breast conservative operation, irradiation for breast is indicated after chemotherapy.
Trastuzumab Monotherapy Arm
The loading dose of trastuzumab is 8 mg/kg of body weight, and the maintenance dose is 6 mg/kg every 3 weeks for 1 year.
If hormone receptor is positive, hormone therapy is indicated. In case of after breast conservative operation, irradiation for breast is indicated after surgery or concurrent with trastuzumab.
(i) Age at registration: 70-75/76-80
(ii) PS: 0/1
(iii) Hormone receptor status: positive/negative
(iv) Pathological nodal status: positive/negative
Main Analysis and Assessment Criteria
To evaluate the clinical position of each treatment, the estimated hazard ratio is compared with a threshold hazard ratio of 1.69. Concretely, the threshold will be used to determine whether the H + CT group is equivalent (not inferior) to the H group with regard to DFS. As an aid to interpret the trial result, we will estimate the three posterior probabilities between and outside the following two thresholds: ‘the upper threshold of hazard ratio (1.69) to select the combination therapy of trastuzumab and chemotherapy' and ‘the lower threshold (1.22) to select the monotherapy of trastuzumab', using the posterior distribution of log hazard ratio based on a non-informative prior.
Sample Size and Follow-up Period
The primary endpoint will require 120 events in total, given a power of 80% and a threshold hazard ratio of 1.69. Giving that the 3-year DFS probability in the study population is 68% and assuming that the survival time follows the exponential distribution, a total of 260 patients will be necessary for 3 years of follow-up after 4 years of registration to assess the 120 events. Therefore, the target number of registration was determined to be 300 since exponential distribution of survival might not be shown because of the elderly population and dropout patients were expected.
This study has been started from October 2009 and completion is scheduled in October 2016 with a registration period for 4 years and a follow-up period for 3 years.
Registration of the Protocol
The protocol was registered at the website of the University Hospital Medical Information Network (UMIN), Japan (protocol ID UMIN000002349), on 1 September 2009. Details are available at the following address: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000002854&language=E.
And also registered at ClinicalTrials.gov (protocol ID NCT01104935), on 6 November 2009. Details are available at the following address: http://clinicaltrials.gov/show/NCT01104935NCT01104935. Previous SectionNext Section
This study is supported by the Public Health Research Foundation, Japan. The corporate and individual sponsors of this study are listed on the CSPOR website (http://www.csp.or.jp/cspor/kyousan_e.html). Previous SectionNext Section
Conflict of interest statement
Hiroji Iwata and Yasuo Ohashi receive honoraria for speaking events from Chugai Pharmaceutical Co., Ltd.Previous Section
. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 2005;353:1673-84.CrossRefMedlineWeb of Science
- Romond EH,
- Perez EA,
- Bryant J,
- Suman VJ,
- Geyer CE Jr.,
- Davidson NE,
- et al
. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 2005;353:1659-72.CrossRefMedlineWeb of Science
- Piccart-Gebhart MJ,
- Procter M,
- Leyland-Jones B,
- Goldhirsch A,
- Untch M,
- Smith I,
- et al
. Phase III randomized trial comparing doxorubicin and cyclophosphamide followed by docetaxel (AC → T) with doxorubicin and cyclophosphamide followed by docetaxel and trastuzumab (AC → TH) with docetaxel, carboplatin and trastuzumab (TCH) in HER2 positive early breast cancer patients: BCIRG 006 study. Breast Cancer Res Treat 2005;94:S5.
- Slamon D,
- Eiermann W,
- Robert N,
- Pienkowski T,
- Martin M,
- Pawlicki M,
- et al
. 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet 2007;369:29-36.CrossRefMedline
- Smith I,
- Procter M,
- Gelber RD,
- Guillaume S,
- Feyereislova A,
- Dowsett M,
- et al
. Adjuvant trastuzumab therapy for HER2-positive breast cancer. Clin Breast Cancer 2008;8:324-33.CrossRefMedlineWeb of Science
- Jahanzeb M
- ↵Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005;365:1687-717.CrossRefMedlineWeb of Science
. Congestive heart failure in older women treated with adjuvant anthracycline chemotherapy for breast cancer. J Clin Oncol 2007;25:3808-15.Abstract/FREE Full Text
- Pinder MC,
- Duan Z,
- Goodwin JS,
- Hortobagyi GN,
- Giordano SH
. Cardiac toxicity associated with anthracycline-containing chemotherapy in older women with breast cancer. Cancer 2009;115:5296-308.CrossRefMedlineWeb of Science
- Du XL,
- Xia R,
- Liu CC,
- Cormier JN,
- Xing Y,
- Hardy D,
- et al
. Acute myeloid leukemia after adjuvant breast cancer therapy in older women: understanding risk. J Clin Oncol 2007;25:3871-6.Abstract/FREE Full Text
- Patt DA,
- Duan Z,
- Fang S,
- Hortobagyi GN,
- Giordano SH
Doctor told me regarding my prognosis that I WASN'T on the Titanic! Hmmm...Really?....Okay! 02/2010 Pure Mucinous Breast Cancer, Oncotype DX 15, Stage 1, Grade 1, 1.8 cm, 0/2 nodes, ER+ 90% /PR+ 70% HER2- (+1)