Drugs of interest to pathologists
Drugs related to surgical pathology
Lapatinib ditosylate

Author: Him G. Kwee, M.D. (see Authors page)

Revised: 5 December 2017, last major update November 2011

Copyright: (c) 2002-2017, PathologyOutlines.com, Inc.

PubMed Search: Lapatinib [title] "loattrfree full text"[sb] review

Cite this page: Kwee, H.G. Lapatinib ditosylate. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/drugstykerb.html. Accessed December 17th, 2017.
Definition / general
  • Dual kinase inhibitor targeting the ErbB-1 (HER1) and Erb-2 (HER2) receptors
Trade name
  • Tykerb® (in U.S.), Tyverb® (in Europe)
Clinical information
Approved by U.S. Food and Drug Administration for:
  • Advanced or metastatic breast carcinoma that overexpress HER2, in combination with capecitabine (Xeloda) in patients who had received prior treatment with an anthracycline, a taxane or trastuzumab (Herceptin, approved March 13, 2007)
  • First line therapy for advanced or metastatic breast carcinomas that are triple positive (ER+, EGFR+ and HER2+) combined with letrozole (Femara) in postmenopausal women (February 2010, source: drug package insert)
  • Approximate cost: $5,000 - $6,000 per month in 2010 (Diseases, Drugs, Health News Dec 10, 2010)
Pathophysiology
  • Lapatinib reversibly binds to the cytoplasmic ATP binding site of the tyrosine kinase domain and blocks receptor phosphorylation and activation, thereby blocking downstream signaling pathways, namely, activation of extracellular signal related kinase 1/2 and phosphatidylinositol 3-Kinase AKT (Oncologist 2007;12:756)
  • Lapatinib is a small molecule able to penetrate the blood brain barrier and may be effective for CNS metastases
  • Lapatinib appears to have clinical activity in inflammatory HER2+ breast carcinoma
  • There is no cross resistance between lapatinib and trastuzumab
  • Common side effect is a characteristic skin rash with inflammatory papules and pustules, usually on the face, neck and back, which may resemble folliculitis and acneiform drug eruption; rash differs from classic acne vulgaris because it lacks comedones
  • Histologically, there is suppurative folliculitis and superficial perifolliculitis with no microcomedones
  • Similar rash can be seen with erlotinib, gefitinib and cetuximab (Oncologist 2007;12:756)
  • Patients who developed such a rash survived twice as long as those who did not develop a rash (RxPG News June 5, 2006)