A review of lapatinib ditosylate in the treatment of refractory or advanced breast cancer

Figures & data

Table 2 Clinical trials involving lapatinib in patients with breast cancer

Author	Study phase	Sample size	Cancer	Lapatinib’s place in therapy	Lapatinib regimen	Effi cacy outcomes (% of study population)
Storniolo et al 2005	I	27	Metastatic breast cancer	2nd-line treatment used in combination regimen	750–1500 mg daily plus trastuzumab	Patients receiving lapatinib were noted to have achieved: 6 complete or partial responses (22%), and 10 disease stabilizations (37%)
						Time to progression and overall survival not reported
Blackwell et al 2005	II	81	Metastatic breast cancer	2nd-line treatment used as monotherapy	Not reported	Patients receiving lapatinib were noted to have achieved: 7 complete or partial responses (9%) and 12 disease stabilizations (15%)
						Time to progression and overall survival not reported
Gomez et al 2005	II	13	Advanced or metastatic breast cancer	1st-line treatment used as monotherapy	1500 mg daily or 500 mg twice daily	Patients receiving lapatinib were noted to have achieved: 5 partial responses (39%) and 6 disease stabilizations (46%)
						Time to progression and overall survival not reported
Spector et al 2006	II	17	Relapsed or refractory inflamatory breast cancer	2nd-line treatment used as monotherapy	1500 mg daily	Patients receiving lapatinib were noted to have achieved: 8 complete or partial responses (47%)
						Time to progression and overall survival not reported All responders were overexpressors of Erb2 (11 of the 17 patients)
Geyer et al 2006	III	321	Refractory advanced metastatic breast cancer	2nd-line treatment used in combination regimen	1250 mg daily plus capecitabine 2000 mg/m^2 on days 1–14 of 3-week cycle (vs. capecitabine monotherapy)	Patients receiving lapatinib were noted to have achieved: 23 complete or partial responses (15%) Median time to progression significantly favored patients treated with lapatinib and capecitabine (37 weeks) compared to patients treated with only capecitabine (20 weeks)

**Table includes studies that focused on breast cancer.

Table 1 Lapatinib in brief

Mechanism of action	Receptor tyrosine kinase inhibitor at ErbB-1 and ErbB-2
Route of administration	Oral as lapatinib ditosylate
Daily dose range	750–1500 mg given once or twice daily
Metabolism	CYP3A4/5 and CYP2C19
Common adverse effects	Rash, diarrhea, nausea, fatigue, anorexia
Drug-drug interactions	CYP450 inhibitors may increase AUC of lapatinib
	CYP450 inducers may decrease AUC of lapatinib

StornioloAMBurrisHPegramMA phase I, open-label study of lapatinib (GW572016) plus trastuzumab; a clinically active regimenProc Am Soc Clin Oncol200523559

 PubMed Web of Science ®Google Scholar

BlackwellKLBursteinHPegramMDetermining relevant biomarkers from tissue and serum that may predict response to single agent lapatinib in trastuzumab refractory metastatic breast cancerProc Am Soc Clin Oncol2005233004

 Web of Science ®Google Scholar

GomezHLChavezMADovalDCA phase II, randomized trial using the small molecule tyrosine kinase inhibitor lapatinib as a first-line treatment in patients with FISH positive advanced or metastatic breast cancerProc Am Soc Clin Oncol2005233046

 Google Scholar

SpectorNLBlackwellKLHurleyJEGF103009, a phase II trial of lapatinib monotherapy in patients with relapsed/refractory inflammatory breast cancer (IBC): Clinical activity and biologic predictors of responseJournal of Clinical Oncology200624502

 Web of Science ®Google Scholar

GeyerCECameronDWLindquistSA phase III randomized, open-label international study comparing lapatinib and capecitabine vs capecitabine in women with refractory advanced or metastatic breast cancer (EGF100151)2006The 42nd Annual Meeting of the American Society of Clinical OncologyAtlanta, GA

 Google Scholar