Global Insight Perspective | |
Significance | The first such type of study demonstrates an improvement in the prognosis of metastatic breast cancer patients undergoing combination therapy with the two currently marketed HER-2 receptor inhibitors. |
Implications | The study brings new hopes to metastatic and hard-to-treat patients, while it demonstrates a synergy between the two rival drugs. |
Outlook | If public and private insurers see the cost of the combination therapy as an effective use of their resources, this could significantly boost Tykerb's sales while the drug completes clinical studies that will support its regulatory filing in additional indications. As for Roche, for now it can relax as GSK touts the use of Tykerb in addition to, rather than in place of, Herceptin. |
U.K. pharmaceutical company GlaxoSmithKline (GSK) has published positive Phase III clinical data for its oncology treatment Tykerb/Tyverb (lapatinib) when used in combination with Herceptin (trastuzumab; Genentech, Roche; U.S., Switzerland) in heavily pre-treated metastatic HER2-positive breast cancer patients. The randomised, open-label trial was conducted in 296 patients who had previously received an unsuccessful median of six anti-cancer treatments, of which a median of three unsuccessful treatments were with Herceptin. As a result, these patients were treated either with Tykerb (1500 mg QD) or Tykerb (1000 mg QD) plus Herceptin (2 mg/kg weekly upon a 4-mg/kg initial dose). The primary trial endpoint was progression-free survival (PFS), while secondary endpoints were response rate (rate of full or partial tumour disappearance), clinical benefit rate (response rate and length of progression-free disease), and overall survival. Results were as follows:
- Patients in the combination arm of the trial experienced a statistically significant increase in their median PFS (12 weeks) compared to patients on the Tykerb arm of the trial (8.1 weeks).
- Patients in the combination arm of the trial saw their risk of disease progression decrease by 27%.
- Patients in the combination arm of the trial had a response rate of 10.3%, while patients on the Tykerb arm of the trial had a response rate of 6.9%.
- Patients in the combination arm of the trial experienced an overall clinical benefit rate twice as high as those in the Tykerb arm of the trial (24.7% versus 12.4%).
- Patients in the combination arm of the trial showed improved overall survival.
- Three out of the 296 patients suffered from symptomatic decreases in left-ventricule ejection fracture (LVEF), two of which belonged to the combination arm of the study
This is the first-ever set of results for Tykerb-Herceptin combination therapy in Tykerb's licensed indication. Tykerb is currently approved in the United States and recommended for approval in Europe for use in HER-2 positive advanced or metastatic breast cancer patients who have previously been treated for their conditions with anthracyclines, taxanes, or trastuzumab (see United Kingdom: 25 April 2008: GSK Makes Progress on European Marketing Authorisation for Breast Cancer Drug Tyverb). Last year, GSK compared the two drugs head-to-head when administered after surgery. Earlier this week, the British giant announced the initiation of the long-awaited head-to-head comparison of the two drugs in first-line treatment (see United Kingdom: 13 May 2008: GSK Starts Tykerb-Herceptin Head-to-Head Phase III Trial in Early Breast Cancer).
Both drugs inhibit the HER-2 receptor, Herceptin does so at the extra-cellular level, but Tykerb does so at the intra-cellular level. Over-expression of the HER-2 receptor stimulates cell proliferation and tumour growth and is associated with poor prognosis. HER-2-positive patients are believed to account for around 25% of all breast cancer cases. Tykerb is the first once-daily oral dual tyrosine kinase inhibitor as it inhibits two receptors (ErbB1, (EGFR) and ErbB2 (HER-2/neu)) involved in cell proliferation.
The company has also announced that additional clinical trial results in breast cancer will be announced at the annual American Society of Clinical Oncology (ASCO), which begins next week on 30 April.
Outlook and Implications
The results of the trial bring new hopes to patients with late-stage aggressive forms of the disease who are not adequately aided by treatment with Herceptin alone. They also come in handy for GSK as they may boost sales of its drug while Tykerb completes clinical assessments in other solid tumour cancers, such as lung cancer and in early breast cancer settings. For now, Tykerb is realising a fraction of its sales potential, which is estimated to reach US$1.35 billion by 2010 in the breast cancer indication alone. Indeed, in the first quarter of the year, the drug generated £19 million (US$36.97 million) in revenues. Nevertheless, to reach full potential, the drug needs to secure reimbursement, a goal that it has so far failed to achieve in the world's largest market, the United States. Offering significant life extension to women affected by the disease when used in combination with Herceptin could boost the prescription of the drug. However, it might be hard to convince cost-effectiveness watchdogs that such combination therapy is an effective use of health budgets.
The results are rather good news to Roche as they demonstrate that metastatic breast cancer patients achieve greater benefits if Tykerb is added to Herceptin rather than if they are switched to Tykerb. This means that if patients are put on combination treatment, sales of Herceptin will not be eroded by those of Tykerb. First-quarter sales of Herceptin stood at 1.22 billion Swiss francs (US$1.15 billion).