Role of lapatinib alone or in combination in the treatment of HER2-positive breast cancer

Figures & data

Table 1A Ongoing clinical trials of lapatinib in the metastatic setting: lapatinib plus chemotherapy

Study	Status	Patient population	Study design and treatment regimen	Phase	N
NCT00496366	Ongoing	First-line for HER2+, stage III/IV	Single-arm, open-label, capecitabine + lapatinib	II	11
NCT00721630	Ongoing	HER2+ MBC	Single-arm, open-label, capecitabine + lapatinib	II	24
NCT00903656	Ongoing	HER2+, advanced or MBC	Single-arm, open-label, doxorubicin + lapatinib	II	30
NCT00508274	Ongoing	HER2+, stage III/IV	Open label, capecitabine + lapatinib	III	52
NCT00820222	Ongoing	HER2+ MBC	Randomized, capecitabine + lapatinib or trastuzumab	III	650
NCT00667251	Ongoing	HER2+ MBC	Randomized, docetaxel or paclitaxel with lapatinib vs trastuzumab	III	600
NCT00281658	Ongoing	HER2+ MBC	Randomized, double-blind, paclitaxel ± lapatinib	III	444
NCT00709618	Ongoing	First-/second-line HER2+ MBC	Single-arm, open-label, vinorelbine + lapatinib	II	60
NCT00709761	Ongoing	First-/second-line HER2+ MBC	Single-arm, open-label, nab-paclitaxel + lapatinib	II	60
NCT00272987	Ongoing	HER2+ MBC	Open-label, paclitaxel + trastuzumab + lapatinib	III	63
NCT01128543	Ongoing	HER2+ MBC	Single-arm, open-label, vinorelbine + lapatinib	II	29
NCT00829166	Ongoing	Trastuzumab refractory, HER2+	Randomized, open-label, trastuzumab emtansine vs capecitabine + lapatinib	III	980
NCT01013740	Ongoing	First-/second-line HER2+ MBC	Randomized, open-label, vinorelbine + lapatinib vs capecitabine + lapatinib	II	105

Abbreviations: HER2+, HER2 positive; MBC, metastatic breast cancer; vs, versus.

Table 1B Ongoing clinical trials of lapatinib in the metastatic setting: lapatinib plus nonchemotherapeutic agents

Study	Status	Patient population	Study design and treatment regimen	Phase	N
NCT00558103	Ongoing	HER+ inflammatory breast cancer	Randomized, double-blind, lapatinib ± pazopanib	III	360
NCT01272141	Ongoing	Triple negative, advanced or MBC	Single-arm, open-label, everolimus + lapatinib	II	43
NCT00470704	Ongoing	HER2+ MBC	Single-arm, open-label, trastuzumab + lapatinib	III	85
NCT00390455	Ongoing	HR+, stage III/IV	Randomized, double-blind, fulvestrant + lapatinib	III	324
NCT00688194	Ongoing	HER2−, HR+ MBC	Randomized, double-blind, fulvestrant + AI + lapatinib	III	396
NCT00118157	Ongoing	HR+, tamoxifen resistant	Single-arm, open-label, tamoxifen + lapatinib	II	19
NCT01499160	Ongoing	HR+, advanced or MBC	Single-arm, open-label, letrozole + lapatinib + everolimus	II	76
NCT00968968	Ongoing	Trastuzumab-pretreated HER2+ MBC	Randomized, open-label, trastuzumab + lapatinib vs trastuzumab maintenance therapy	III	280
NCT01160211	Ongoing	First-line HER2+, HR+ MBC	Randomized, three-arm, open-label, Ai + trastuzumab and/or lapatinib	III	525

Abbreviations: AI, aromatase inhibitor; HER2−, human epidermal growth factor receptor 2 negative; HER2+, human epidermal growth factor receptor 2 positive; HR+, hormone receptor positive; MBC, metastatic breast cancer.

Table 2 Summary of Phase iii trials of lapatinib in combination with other agents

Study	N	Patients	Treatment	Outcomes
Lapatinib + nonchemotherapeutic agents
Schwartzberg et al^Citation108	219*	First-line HR+,HER2+ MBC	Lapatinib ± letrozole	PFS: 3.0 vs 8.2 months; HR: 0.71; P = 0.019 ORR: 15% vs 28%; P = 0.021 CBR: 29% vs 48%; P = 0.003 OS: 32.3 vs 33.3 months (P-value not reported)
Blackwell et al^Citation72,Citation73	296	HER2+, trastuzumab refractory MBC	Lapatinib ± trastuzumab	PFS: 8.1 vs 12.0 weeks; HR: 0.73; P = 0.008 ORR: 6.9% vs 10.3%; P = 0.46 CBR: 12.4% vs 24.7%; P = 0.01 Final OS: 9.5 vs 14.0 months; HR: 0.74; P = 0.026
Chemotherapeutic agents ± lapatinib
Geyer et al^Citation11	399	HER2+, trastuzumab refractory MBC	Capecitabine ± lapatinib	PFS: 4.4 vs 8.4 months; HR: 0.47; P < 0.001 ORR: 14% vs 22%; P = 0.09 CBR: 29% vs 44% Death: 22% vs 22%; HR: 0.92; P = 0.72
Di Leo et al^Citation84	86**	First-line MBC	Paclitaxel ± lapatinib	PFS: 25.1 vs 36.4 weeks; HR: 0.53; P = 0.005 ORR: 37.8% vs 63.3%; P = 0.023 CBR: 40.5% vs 69.4%; P = 0.011 OS: 82.4 vs 104.6 weeks; HR: 0.74; P = 0.365
Neoadjuvant administration of lapatinib
Baselga et al^Citation96	455	Invasive, operable, HER2+	Lapatinib and/or trastuzumab***	pCR: 24.7% vs 29.5% vs 51.3%; P = 0.34 (lapatinib vs trastuzumab); P = 0.0001 (lapatinib + trastuzumab vs trastuzumab) ORR: 52.6% vs 30.2% vs 67.1%; P < 0.001 (lapatinib vs trastuzumab); P < 0.001 (lapatinib + trastuzumab vs trastuzumab)
Untch et al^Citation94	620	Locally advanced, HER2+	Lapatinib vs trastuzumab****	pCR: 21.7% vs 31.3%; P < 0.03

Notes:

* Study enrolled a total of 1286 patients (219 were HER2+); the outcome data presented here are from the HER2+ patients;

** study enrolled a total of 579 patients (only 86 were HER2+); the outcome data presented here are from the HER2+ patients;

*** therapy administered for 6 weeks followed by 12 weeks of same therapy plus weekly paclitaxel;

**** therapy administered with epirubicin, cyclophosphamide, and docetaxel.

Abbreviations: CBR, clinical benefit rate; HER2+, human epidermal growth factor receptor 2 positive; HR, hazard ratio; HR+, hormone receptor positive; MBC, metastatic breast cancer; ORR, overall response rate; OS, overall survival; pCR, pathologic complete response; PFS, progression-free survival; vs, versus.

Table 3 Ongoing clinical trials of lapatinib in the neoadjuvant and the adjuvant setting

Study	Patient population	Study design and treatment regimen	Phase	N
NCT00499681	HER2+ and HR+, operable	Randomized, double-blind, neoadjuvant letrozole ± lapatinib	II	6
NCT00769470	HER2+, operable	Randomized, open-label, neoadjuvant TC + lapatinib and/or trastuzumab	II	140
NCT00486668	HER2+, operable	Randomized, open-label, neoadjuvant AC-T + trastuzumab and/or lapatinib	III	529
NCT00206427	HER2+, stage III/IV	Nonrandomized, open-label, neoadjuvant lapatinib	II	55
NCT00548184	HER2+, locally advanced	Randomized, neoadjuvant trastuzumab ± lapatinib and endocrine therapy	II	64
NCT00422903	HER2−, HR+, operable	Randomized, double-blind, neoadjuvant letrozole ± lapatinib	II	91
NCT00756470	HER2+ inflammatory breast cancer	Single-arm, open-label, neoadjuvant paclitaxel-FEC + lapatinib	II	60
NCT00429299	HER2+, locally advanced	Randomized, open-label, neoadjuvant chemotherapy + lapatinib and/or trastuzumab	IIb	120
NCT00770809	HER2+, operable	Randomized, neoadjuvant paclitaxel + lapatinib and/or trastuzumab	III	400
NCT00490139	HER2+, operable	Randomized, open-label, adjuvant chemotherapy + lapatinib and/or trastuzumab	III	8381
NCT01309607	HER2+, stages I–III	Single-arm, open-label, neoadjuvant paclitaxel + carboplatin + lapatinib	II	34
NCT01485926	HER2+, locally advanced	Randomized, open-label, neoadjuvant TC + lapatinib and/or trastuzumab	II	120
NCT01205217	HER2+, stages I–III	Randomized, open-label, neoadjuvant EC-T + lapatinib vs trastuzumab	II	164
NCT00374322	HER2+ early stage	Randomized, double-blind, adjuvant lapatinib	III	3000
NCT01275859	HER2+, HR+, locally advanced	Single-arm, open-label, neoadjuvant letrozole + lapatinib	II	32
NCT00841828	HER2+, locally advanced	Randomized, open-label, neoadjuvant EC-docetaxel + lapatinib vs trastuzumab	II	102
NCT00553358	HER2+, locally advanced	Randomized, open-label, neoadjuvant paclitaxel + lapatinib and/or trastuzumab	III	455
NCT00999804	HER2+, locally advanced	Randomized, open-label, neoadjuvant lapatinib + trastuzumab + letrozole	II	96
NCT00524303	HER2+, locally advanced	Randomized, open-label, FEC-paclitaxel + lapatinib and/or trastuzumab	II	100
NCT01104571	HER2+, operable	Randomized, open-label, neoadjuvant and adjuvant trastuzumab vs lapatinib	III	250

Abbreviations: AC-T, doxorubicin, cyclophosphamide, paclitaxel; EC, epirubicin, cyclophosphamide; EC-T, epirubicin, cyclophosphamide, paclitaxel; FEC, 5-fluorouracil, epirubicin, cyclophosphamide; HER2−, human epidermal growth factor receptor 2 negative; HER2+, human epidermal growth factor receptor 2 positive; HR+, hormone receptor positive; TC, docetaxel, carboplatin; vs, versus.

Table 4 Ongoing clinical trials of lapatinib in patients with central nervous system (CNS) metastases

Study	Status	Patient population	Study design and treatment regimen	Phase	N
NCT00263588	Ongoing	HER2+ with CNS metastases after trastuzumab-based regimen and WBRT	Single-arm, open-label, lapatinib	II	242
NCT00470847	Ongoing	HER2+ with CNS metastases	Single-arm, open-label, WBRT + lapatinib	II	39
NCT00614978	Ongoing	HER2+ with CNS relapse	Single-arm, open-label, temozolomide + lapatinib	I	18
NCT00967031	Ongoing	HER2+ with CNS metastases	Single-arm, open-label, capecitabine + lapatinib	II	45
NCT01218529	Ongoing	Lung or breast cancer with CNS metastases	Single-arm, open-label, WBRT + lapatinib	II	81

Abbreviations: HER2+, human epidermal growth factor receptor 2 positive; WBRT, whole-brain radiotherapy.

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