Role of lapatinib in the first-line treatment of patients with metastatic breast cancer

Figures & data

Figure 1 Chemical structure of lapatinib.

Table 1 First-line lapatinib trials in metastatic breast cancer

Reference	Trial	Population	Pts	Therapy	Outcomes
Gomez et al^Citation13	Phase II Multicenter, randomized, open label	HER2-positive advanced or MBC	138	Lapatinib 500 mg twice daily (n = 69) vs Lapatinib 1500 mg once daily (n = 69)	ORR 24% CBR 31% PFS 16.1 wk Equal efficacy between doses
Di Leo et al^Citation17	Phase III Multicenter, randomized, double-blind, placebo-controlled	HER2-negative or unknown advanced or MBC	579	Lapatinib 1500 mg once daily plus paclitaxel 175 mg/m^2 iv every 21 days (n = 291) vs Placebo plus paclitaxel 175 mg/m^2 iv every 21 days (n = 288)	ITT population: ORR 35.1% vs 25.3% P = 0.008 CBR 40.5% vs 31.9% P = 0.025 EFS 25.1 wk vs 22.6 wk P = 0.238 HER2-positive (n = 86): (retrospective analysis) ORR 63.3% vs 37.8% P = 0.023 CBR 69.4% vs 40.5% P = 0.011 EFS 35.1 wk vs 21.9 wk P = 0.004
Johnston et al^Citation18	Phase III Multicenter, randomized, double-blind, placebo control	HR-positive MBC in postmenopausal women	1286	Lapatinib 1500 mg once daily plus letrozole 2.5 mg once daily (n = 642) vs Placebo plus letrozole 2.5 mg once daily (n = 644)	ITT population: ORR 33% vs 32% P = 0.726 CBR 58% vs 56% P = 0.761 PFS 11.9 mo vs 10.8 mo, P = 0.026 HER2-positive pts (n = 219): ORR 28% vs 15%, P = 0.021 CBR 48% vs 29%, P = 0.003 PFS 8.2 mo vs 3 mo, P = 0.019

Abbreviations: CBR, clinical benefit rate; EFS, event-free survival; HR, hormone receptor; ITT, intent to treat; IV, intravenous; MBC, metastatic breast cancer; MO, months; ORR, objective response rate; PFS, progression-free survival; Pts, patients; WK, weeks.

Table 2 National Cancer Institute Common Toxicity Criteria (NCI-CTC) grading for diarrhea

Toxicity grade	Diarrhea
1	Increase of <4 stools/day over baseline Mild increase in ostomy output compared with baseline
2	Increase of 4–6 stools/day over baseline Intravenous fluids >24 h Moderate increase in ostomy output compared with baseline Not interfering with daily living
3	Increase of >7 stools/day over baseline Incontinence Intravenous fluids Severe increase in ostomy output compared with baseline Interfering with daily living activities
4	Life-threatening consequences (eg, hemodynamic collapse)
5	Death

GomezHLDovalDCChavezMAEfficacy and safety of lapatinib as first-line therapy for ErbB2-amplified locally advanced or metastatic breast cancerJ Clin Oncol2008182999300518458039

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Di LeoAGomezHLAzizZPhase III, double-blind, randomized study comparing lapatinib plus paclitaxel with placebo plus paclitaxel as first-line treatment for metastatic breast cancerJ Clin Oncol2008345544555218955454

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JohnstonSPippenPPivotXLapatinib combined with letrozole versus letrozole and placebo as first-line therapy for postmenopausal hormone receptor–positive metastatic breast cancerJ Clin Oncol2009275538554619786658

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