New combination of targeted therapies shows promising results in HER2-positive metastatic breast cancer patients

Wednesday, 04 Jan 2012

Singapore, 04 Jan 2012– A recent study on HER2-positive metastatic or advanced breast cancer patients has reported improvement in their treatment outcome with a new combination of targeted therapies.

Approximately 20% of breast cancers are HER2-positive, or overexpress the human epidermal growth factor 2 (HER2) protein. This subset of breast cancers is typically more aggressive, but advances in treatment have improved the outcome of patients considerably over the past decade.

The study, known as ‘The Clinical Evaluation of Pertuzumab and Trastuzumab (CLEOPATRA)”, assessed the efficacy and safety of two different regimens as first line treatment for HER2-positive metastatic breast cancer using the combination of pertuzumab, trastuzumab and docetaxel (experimental arm) versus the combination of placebo, trastuzumab and docetaxel (control arm). Trastuzumab (Herceptin) is a humanized monoclonal antibody that targets HER2, and has been widely used over the past decade, while pertuzumab is a new anti-HER2 antibody with activity which is complementary to that of trastuzumab. Docetaxel is a chemotherapy drug used in breast, lung, prostate and other cancers.

This study, which was conducted by F-Hoffman La Roche/Genentech, a member of the Roche pharmaceutical group, was on patients who had locally recurrent, unresectable or metastatic HER2-positive breast cancer, and who had not received chemotherapy or biologic therapy for their metastatic disease. A total of 808 patients in 25 countries participated in this study. Among the 808 patients who took part, 406 were randomly assigned to placebo, trastuzumab and docetaxel (control group), and 402 to pertuzumab, trastuzumab and docetaxel (pertuzumab group). Treatment was administered intravenously every 3 weeks. The docetaxel chemotherapy could be discontinued in the event of significant toxicity, and patients could continue on the combination of trastuzumab and pertuzumab/placebo until the disease progressed (i.e. worsened), the toxicities became unmanageable, or if the patients(s) withdrew consent.

The latest results presented at the San Antonio Breast Cancer Symposium in Texas, USA, and published online in the New England Journal of Medicine in December 2011 reported that the addition of pertuzumab had significantly improved progression-free survival by 6.1 months, from 12.4 months in the control group to 18.5 months in the pertuzumab group. This means that duration of control of the cancer was prolonged by approximately 6.1 months with the addition of pertuzumab.

Although the overall survival results are not yet mature, there was a strong indication of survival benefit with the pertuzumab group. Interim analysis revealed more deaths in the control group than the pertuzumab group (96 deaths versus 69 deaths).

Current standard of care for patients with HER2-positive metastatic breast cancer includes a combination of trastuzumab and chemotherapy. Lapatinib is another drug that is approved for use in HER2-positive breast cancer. Although trastuzumab and lapatinib have improved treatment outcomes significantly, resistance to therapy ensues and patients eventually experience deterioration of their condition with the cancer progressing. There is a constant need to discover newer and more effective therapies to combat cancer.

Mrs T was one of the ten patients from NCCS who participated in the CLEOPATRA study. Mrs T, who prefers to remain anonymous, was diagnosed with stage 2 breast cancer in 2002 at the age of 53. After mastectomy, she underwent chemotherapy and radiation therapy to reduce the risk of relapse, ie to prevent the cancer from coming back. Six years later, in late 2008, the cancer had recurred and metastasized to the liver. She opted to take part in the CLEOPATRA trial in early 2009 to give herself the chance of winning her battle against cancer, although she does not know if she is getting the new experimental drug. The CLEOPATRA study is a double-blind trial, ie neither the doctor nor patient knows which group the patients have been assigned to, in order to minimise any bias with reporting of results.

Mrs T received docetaxel chemotherapy for the first nine cycles of treatment until she developed numbness in her hands and feet. She remains on trastuzumab and pertuzumab/placebo, and goes to National Cancer Centre Singapore every 3 weeks for her intravenous treatment. Every nine weeks, she undergoes CT scan of her chest and abdomen to check the status of her cancer.

Mrs T has been tolerating her treatment well and is currently up to her 50th cycle of treatment. She is now 62 years old and has been in remission since she enrolled in the study nearly 3 years ago. “Even though it is a trial, it’s a double blind study, so you don’t know if you get the new drug. I thought, ‘Why not?’ Maybe the new drug will have more breakthroughs. In this trial, expenses are covered and if I get the new drug, then I would be getting better that much more,” she said. “I was initially devastated when diagnosed with the relapse, but my condition has improved with the treatment and I have remained in remission. I wish to share my story with other cancer patients to encourage them in their fight against cancer.

Dr Yap Yoon Sim, Senior Consultant, Department of Medical Oncology at National Cancer Centre Singapore, who is treating Mrs T, said the signs are very encouraging.

“The problem is that we can’t tell patients they have been cured of the cancer because stage four cancers in the context of most cancers are not curable.

But with improvement in treatment options, it may not be impossible in the future for certain conditions. That’s why it’s really important to support, conduct and to participate in research. Without research, no advances in knowledge and no improvements in treatment outcome will be achieved.”

For further information, please contact:

Ms Veronica Lee
Senior Executive, Corporate Communications
Tel: 6236 9429 / 9450 4017
Email: Veronica.Lee.H.E@nccs.com.sg

Ms Charissa Eng
Executive, Corporate Communications
Tel: 6236 9424 / 9171 6021
Email: Charissa.Eng@nccs.com.sg

About NCCS

The National Cancer Centre Singapore (NCCS) is the cancer centre dedicated to providing a holistic and multidisciplinary approach to cancer treatment and patient care. We treat almost 70 per cent of the public sector oncology cases. Through the subspecialisation of its oncology, patients can receive the best in treatment and care. NCCS is engaged in cutting-edge clinical and translational research which has received several international acclaims. The national centre is accredited by the Joint Commission International in 2010 for quality patient care and safety.

NCCS, which is set to be a global leading institution, also offers specialist training programmes to other medical institutions here and overseas.