Product
Tykerb

Approval Date
March 13, 2007
 
Release Date
May 7, 2007
 
Company
GlaxoSmithKline
 
Class
Antineoplastic (tyrosine kinase inhibitor)
 

Indication

In combination with capecitabine, for the treatment ofpatients with advanced or metastatic breast cancer whose tumors overexpressHER2 and who have received prior therapy including an anthracycline, a taxane,and trastuzumab.
 
Active Ingredient
Lapatinib 250mg; tabs.
 
Agency Roster
Torre Lazur McCann (professional)
LifeBrands (strategy development)

MarketingStrategy/Execution

Tykerb was launched within a week after its March 13 US approval, aspeed appropriate given the serious nature of HER2 metastatic breast cancer. WhileGlaxoSmithKline declined to comment on its marketing strategy, Tykerb appearsto be gaining ground in the metastatic breast cancer market, as its chiefcompetitor on that front, Genentech’s Herceptin, posted weaker third-quarterperformance. As of July, Tykerb had almost 50% of patients receiving HER2targeted therapy in the third line or later setting and about 16% of its use insecond line or earlier, according to Glaxo. An extensive clinical trial programin breast cancer and other cancers is ongoing.

The Market

Tyrosine kinase inhibitors US sales ($000s) last 5 years
2006

$438,679

2005

$355,571

2004

$234,858

2003

$94,316

2002
Source: IMS Health, Oct. 2007

 

Top 3 Tyrosine kinase inhibitors
  Jan.-July ’07 US sales ($000s) % sales growth over Jan.-July ‘06

TARCEVA(Genentech)

267,669

14

TYKERB(GlaxoSmithKline)

29,063

***

IRESSA(AstraZeneca)

6,278

-46
Source: IMS Health, Oct. 2007

Physician Outlook
Tykerb (lapatanib), an orally administered inhibitor ofthe HER1 and HER2 receptors, represents an important new treatment optionfor women with HER2-positive metastatic breast cancer (MBC) who have failedprior systemic therapy that included Herceptin (trastuzumab; Genentech). Tykerbis approved in combination with Xeloda (capecitabine; Roche), which offers afully oral regimen. GfK Market Measures conducted a short survey ofmedical oncologists about one month after this brand became commerciallyavailable in March 2007, and we found that physicians were keen to adopt thisnew therapy. More than 85% of medical oncologists surveyed had prescribed, orintended to prescribe, Tykerb in the near future for patients withHER2-positive metastatic breast cancer who had progressed on therapy withHerceptin. The market for front-line therapy in HER2-positive MBC will nodoubt become more competitive as positive clinical data for Tykerb becomeavailable in this setting.
—Bill Bowman, JD, VP, category leader, oncology, GfK MarketMeasures, October 2007

Also in the Pipeline(according to Adis R&D Insight)
Drug: PNU-290940/SU 011248/ Sutent
Manufacturer: Pfizer
Indication: Breast cancer, Non-small cell lung cancer,Colorectal cancer, Neuroendocrine tumours, Prostate cancer, Solid tumours
Active Ingredient: Sunitinib malate
Phase: III (Breast cancer, Non-small cell lung cancer), II(Colorectal cancer, Neuroendocrine tumours, Prostate cancer, Solid tumours)
Source: Wolters Kluwer Health, Oct. 2007

Recent MM&MCoverage
FDAapproves GlaxoSmithKline’s Tykerb advanced breast cancer treatment
GSK’sTykerb gets priority review
Productnews from the 03/20/07 news brief
GSKhalts breast cancer trial following positive results
Pipeline 2007
Productnews from the 09/19/06 news brief
GSKgets nod to sell OTC version of diet drug

Pharmacology
Overexpression of epidermal growth factor receptor (EGFR)and human epidermal receptor type 2 (HER2) has been reported in a variety oftumors. Lapatinib works by inhibiting the tyrosine kinase components of theEGFR and HER2 receptors.

Clinical Trials
Lapatinib was evaluated in combination with capecitabine inthe treatment of breast cancer in a randomized, Phase 3 trial that enrolled 399patients. The patients had HER2 overexpressing locally-advanced or metastaticbreast cancer that had progressed following prior treatment withanthracyclines, taxanes, and trastuzumab. Capecitabine was given on Days 1–14on a 21-day cycle, and lapatinib was given once daily continuously. Theendpoint was time to progression (time from randomization to tumor progressionor death due to breast cancer). An interim analysis revealed that, according toan independent assessment, the median time to progression in the group givenlapatinib + capecitabine was 27.1 weeks compared to 18.6 weeks for capecitabineonly. The response rate was 23.7% for the lapatinib + capecitabine groupcompared to 13.9% for the capecitabine-only group. Data results frominvestigator assessment was significant as well.

Adverse Reactions
Diarrhea (may be severe), nausea, vomiting, hand/footsyndrome, rash, fatigue; decreased LVEF, QT prolongation.

Adults
Take 1 hour before or 1 hour after a meal. Take once dailyon Days 1–21 continuously with capecitabine (see literature for capecitabinedose) in a repeating 21 day cycle. 1250mg (5 tablets). Severe hepaticdysfunction (Child-Pugh Class C): 750mg (no clinical data for this doseadjustment). After recovery from left ventricular ejection fraction (LVEF)decrease: 1g. Concomitant potent CYP3A4 inhibitors: 500mg (no clinical data forthis dose adjustment). Concomitant potent CYP3A4 inducers: may titrate up to4500mg (no clinical data for this dose adjustment). Discontinue if =Grade 2 NCICTC toxicity occurs; may restart at 1250mg if toxicity improves to grade 1; ifrecurs, may restart at 1g.

Children
Not recommended.

Contraindications
Renal disease or dysfunction. Metabolic acidosis,ketoacidosis. Concomitant intravascular iodinated contrast agents (suspendduring and for 48 hours after use). Type 1 diabetes.

Precautions
Discontinue if =Grade 2 decrease in LVEF occurs, or if LVEFfalls below institution’s lower limit of normal; may restart after at least 2weeks at reduced dose if asymptomatic and LVEF recovers. Conditions that impairleft ventricular function, or risk factors for QT prolongation (eg,hypokalemia, hypomagnesemia, congenital long QT syndrome, concomitantantiarrhythmics, cumulative high dose anthracyclines); correct electrolytedisturbances before starting. Severe hepatic impairment. Pretreat for diarrheawith antimotility drugs. Monitor ECG. Pregnancy (Cat.D). Nursing mothers: notrecommended.

Interactions
Avoid potent CYP3A4 inhibitors (eg, ketoconazole),grapefruit; reduce dose if unavoidable. Avoid potent CYP3A4 inducers (eg,carbamazepine); slowly titrate dose up if unavoidable. May affect drugs thatare affected by p-glycoprotein, CYP2C8.