Tykerb (lapatinib)

Company
GlaxoSmithKline

Approval Status
Approved March 2007

Treatment for
breast cancer

Areas
Cancer & Oncology

Tykerb is an inhibitor of the intracellular tyrosine kinase domains of both Epidermal Growth Factor Receptor (EGFR [ErbB1]) and of Human Epidermal Receptor Type 2 (HER-2 [ErbB2]) receptors. Mutations in either of these receptors have been shown to play a role in cancer.

Tykerb is specifically indicated in combination with capecitabine for the treatment of patients with advanced or metastatic breast cancer whose tumors overexpress HER2 and who have received prior therapy including an anthracycline, a taxane, and trastuzumab.

Tykerb is supplied as a 250 mg tablet designed for oral administration. The recommended initial dose of the drug is 1,250 mg (5 tablets) given orally once daily on days 1-21 continuously in combination with capecitabine 2,000 mg/m2/day (administered orally in 2 doses approximately 12 hours apart) on days 1-14 in a repeating 21 day cycle. Dividing the daily dose is not recommended. Tykerb should be discontinued in patients with decreased left ventricular ejection fraction (LVEF) that is grade 2 or greater by NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) and in patients with an LVEF that drops below the institution’s lower limit of normal. Treatment may be restarted at a reduced daily dose (1,000 mg) after a minimum of two weeks if the LVEF recovers to normal and the patient is asymptomatic. Patients with severe hepatic impairment should have their dose reduced. The concomitant use of stron CYP3A4 inhibitors and inducers should be avoided.If a grade 2 NIC CTC toxicity occurs, discontinuation or interruption with Tykerb may be considered. Treatment can be restarted at 1,250 mg/day when toxicity improves to grade 1 or less.

FDA Approval
FDA approval of Tykerb in combination with capecitabine was based on the results of one clinical trial. This trial enrolled 399 subjects with HER-2 over-expressing locally advanced or metastatic breast cancer, progressing after prior treatment that included anthracyclines, taxanes, and trastuzumab. Subjects were randomized to receive either Tykerb 1,250 mg once daily (continuously) plus capecitabine 2,000 mg/m2/day on Days 1-14 every 21 days, or to receive capecitabine alone at a dose of 2,500 mg/m2/day on Days 1-14 every 21 days. The primary endpoint was time to progression (TTP) defined as time from randomization to tumor progression or death related to breast cancer. The median TTP was 23.9 weeks for the combination treatment versus 18.3 weeks for capecitabine alone, for a response rate of 31.8% versus 17.4%, respectively.

Ongoing Study Commitments

  • GlaxoSmithKline has agreed to perform an in vivo drug interaction study of the ability of steady-state lapatinib dosing to alter the pharmacokinetics of a single dose of midazolam. A positive finding in this study may initiate a need for further studies.
    Protocol Submission: October1, 2005
    Study Start: Ongoing
    Final Report Submission: June 2008
  • GlaxoSmithKline has agreed to perform an in vivo drug interaction study of the ability of steady-state lapatinib dosing to alter the pharmacokinetics of a single dose of paclitaxel or rosiglitazone. A positive finding in this study may initiate a need for further studies.
    Protocol Submission: October 7, 2002
    Study Start: Ongoing
    Final Report Submission: June 2007
  • GlaxoSmithKline has agreed to perform an in vivo drug interaction study of the ability of steady-state lapatinib dosing to alter the pharmacokinetics of a single dose of digoxin. A positive finding in this study may initiate a need for further studies.
    Protocol Submission: September 2007
    Study Start: November 2007
    Final Report Submission: December 2009
  • GlaxoSmithKline has agreed to submitting the results of the survival analysis of Study EGF100151 at 75% of the events.
    Protocol Submission: November 2003
    Study Start: Ongoing
    Final Report Submission: June 2008

Adverse events associated with the use of Tykerb may include, but are not limited to, the following:

  • Diarrhea
  • Palmar-plantar erythrodysesthesia
  • Nausea
  • Rash
  • Vomiting
  • Mucosal inflammation
  • Stomatitis
  • Pain in extremities
  • Dyspnea
  • Fatigue

Tykerb is an inhibitor of the intracellular tyrosine kinase domains of both Epidermal Growth Factor Receptor (EGFR [ErbB1]) and of Human Epidermal Receptor Type 2 (HER-2 [ErbB2]) receptors. When the binding site is blocked signal molecules can no longer attach there and activate the tyrosine kinase, an enzyme which functions to stimulate cell division. The over-expression of EGFR and HER-2 have been associated with a number of cancers, including breast cancer.

For additional information regarding Tykerb or breast cancer, please visit the Tykerb web page.

Tykerb (lapatinib) Drug Information

The Tykerb (lapatinib) drug information shown above is licensed from Thomson CenterWatch. The information provided here is for general educational purposes only and does not constitute medical or pharmaceutical advice which should be sought from qualified medical and pharmaceutical advisers.

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