Results Of First Phase III Trial Evaluating Tykerb(TM) Tablets Plus Herceptin(R) Presented At ASCO

Main Category: Breast Cancer
Also Included In: Clinical Trials / Drug Trials
Article Date: 21 May 2008 - 4:00 PDT

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Data from the first-ever randomized, multi-center, open label Phase III trial examining the combination of two targeted therapies, Tykerb™ (lapatinib ditosylate) tablets and Herceptin® (trastuzumab), in women with HER2-positive metastatic breast cancer1 will be presented at the annual American Society of Clinical Oncology (ASCO) meeting in Chicago. The study results show that Tykerb is active alone and provides added benefit when combined with Herceptin. Both agents target the HER2 protein, otherwise known as ErbB2, but work in different ways.1 Herceptin attaches to the outside of the HER2 protein, while Tykerb works inside the cell blocking signals that cause the cancer cell to grow.3

A marketing application for Tykerb has been submitted to Health Canada, and the file is currently under review.

"HER2-positive breast cancer is generally very difficult to treat because when the disease progresses after treatment with Herceptin and chemotherapy, there are no other targeted therapies available for these patients," said Dr. Kathy Pritchard, Senior Scientist and Medical Oncologist at Sunnybrook's Odette Cancer Centre. "New therapies are needed to give women more options to help control their disease, and give them hope for a longer life."

HER2-positive breast cancer is an extremely aggressive form of cancer that affects approximately 20 per cent of breast cancer patients.2

Prior to enrolment, women in the study had received a median of six prior therapies, including Herceptin alone, and their disease continued to progress. Despite being heavily pre-treated, patients who received Tykerb plus Herceptin experienced:

- A significant increase in median progression-free survival versus Tykerb tablets alone (12 weeks vs 8.1 weeks)1
- A 27 per cent reduction in the risk of disease progression [Hazard Ratio: 0.73; p=0.008]1
- Double the overall clinical benefit rate versus Tykerb tablets alone (24.7 per cent vs. 12.4 per cent; p=0.01).1 Clinical benefit rate is defined as the response rate [complete response (CR) + partial response (PR) and the rate of durable stable disease (SD) (greater than or equal to 6 months).
- A trend in improved overall survival [Hazard Ratio: 0.75; p=0.106].1

The study also demonstrated the activity of Tykerb as a single agent in this patient population, with patients on this arm achieving a median progression free survival of 8.1 weeks and an overall clinical benefit rate of 12.4 per cent.1

Study Background

In this study, 296 patients with HER2-positive breast cancer who had documented progression on Herceptin in the metastatic setting were eligible to be randomized to receive Tykerb tablets (1000 mg daily) plus Herceptin (2 mg/kg weekly after a 4 mg/kg loading dose) or Tykerb alone (1500 mg daily). Patients were heavily pre-treated and had received a median of six prior anti-cancer regimens. Patients had received a median of three prior lines of Herceptin.1

The primary endpoint of the study was progression-free survival, and secondary endpoints included clinical benefit rate (CR+PR+SD ≥24 weeks), response rate, and overall survival. If patients progressed on the Tykerb monotherapy arm after at least four weeks of therapy, they could cross over to receive the combination of Tykerb tablets plus Herceptin.

Adverse events were similar in both arms of the study. In general the treatments were well tolerated. The most common side effects were considered manageable and included diarrhea, nausea and rash. Cardiotoxicity occurred in 6 per cent of patients in the combination arm and 3 per cent in the monotherapy arm, most of which were asymptomatic.

About Tykerb Tablets

Tykerb is an investigational drug that is in a class of cancer treatments called targeted therapies. It is an oral small-molecule inhibitor of the HER2 tyrosine kinase receptor. Stimulation of HER2 is associated with cell proliferation, tumor progression and the development of metastases. Overexpression of this receptor has been reported in a variety of human tumors and is associated with poor prognosis and reduced overall survival.3

A marketing application for Tykerb has been submitted to Health Canada, and the file is currently under review. It has been approved in 27 countries around the world including the United States, and it recently received a positive opinion from the Committee for Medical Products for Human Use (CHMP) of Europe.

Tykerb Clinical Trials

GSK has a comprehensive clinical trial program that is actively studying Tykerb tablets in other breast cancer settings and other cancers to better identify patient populations that may respond to this therapy.

About GlaxoSmithKline

GlaxoSmithKline - one of the world's leading research-based pharmaceutical and health-care companies - is committed to improving the quality of human life by enabling people to do more, feel better and live longer. In Canada, GlaxoSmithKline is among the top 15 investors in research and development, contributing more than $176 million in 2006 alone. GSK is an Imagine Caring Company, and is consistently recognized as one of the 50 Best Employers in Canada.

Notes

Tykerb™ is a trademark of the GlaxoSmithKline.
Herceptin® is a registered trademark of Hoffmann-La Roche Ltd.

References

1. O'Shaughnessy J, et. al. Final presentation for abstract #1015 - A randomized study of lapatinib (TYKERB®) in combination with trastuzumab vs. lapatinib monotherapy in heavily pretreated HER2-positive metastatic breast cancer progressing on trastuzumab therapy. To be presented at the 2008 American Society of Clinical Oncology annual meeting.

2. Slamon DJ, et al. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 1987; 235:177-182.

3. Geyer C, et. al. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med 2006;355:2733-43.

GlaxoSmithKline