Emerging treatments for HER2-positive early-stage breast cancer: focus on neratinib

Figures & data

Table 1 Ongoing clinical trials with neratinib in early-stage breast cancer according to www.clinicaltrials.gov entries until March 2017

NCT number	Phase	Study title	Subjects, n	Status
NCT01008150	II	Phase II randomized trial evaluating neoadjuvant therapy with neratinib and/or trastuzumab followed by postoperative trastuzumab in women with locally advanced HER2-positive breast cancer	141	Active but not recruiting
NCT02400476	II	A study looking at the incidence and severity of diarrhea in patients with early-stage HER2-positive breast cancer treated with neratinib and loperamide	240	Active and recruiting
NCT00878709	III	Study evaluating the effects of neratinib after adjuvant trastuzumab in women with early stage breast cancer (ExteNET)	2,840	Active but not recruiting
NCT01042379	II	I-SPY 2 TRIAL: neoadjuvant and personalized adaptive novel agents to treat breast cancer (I-SPY 2)	1,920	Active and recruiting
NCT01008150	II	Phase II randomized trial evaluating neoadjuvant therapy with neratinib	141	Active but
		and/or trastuzumab followed by postoperative trastuzumab in women with locally advanced HER2-positive breast cancer		not recruiting

Abbreviation: HER2, human epidermal growth factor receptor 2.

Table 2 Available clinical trials with the use of neratinib in early-stage breast cancer

Trial	Study design	Setting/population	Number of patients	Treatment arm	Main results
ExteNET^Citation64	Phase III	Adjuvant setting/stage I–III breast HER2-positive	1,420 1,420	CT + trastuzumab for 1 year + placebo for another year CT + trastuzumab for 1 year + neratinib for another year	2-year IDFS: 91.6% 2-year IDFS: 93.9%
I-SPY 2^Citation67	Phase II	Neoadjuvant setting/stage II/III HER2-positive or -negativea	115 78	CT + neratinib Paclitaxel alone in HER2-negative and with trastuzumab in HER2-positive	pCR in HER2-positive/ER-negative: 56% pCR in HER2-positive/ER-positive: 30% pCR in HER2-positive: 39% pCR in HER2-positive/ER-negative: 33% pCR in HER2-positive/ER-positive: 17% pCR in HER2-positive: 23%
NSABP FB 7^Citation68	Phase II	Neoadjuvant setting/stage IIB/IIIC HER2-positive	126	Paclitaxel + trastuzumab followed by doxorubicin and cylophosphamide Paclitaxel + neratinib followed by doxorubicin and cylophosphamide Paclitaxel + neratinib + trastuzumab followed by doxorubicin and cyclophosphamide	pCR: 38% pCR: 33% pCR: 50%

Note:

a There was limited activity of neratinib in patients with HER2-negative disease independently of their hormonal receptor status, and the adaptive randomization algorithm stopped assigning these patients to receive the anti-HER2 tyrosine kinase inhibitor.

Abbreviations: CT, chemotherapy; ER, estrogen receptor; HER2, human epidermal growth factor receptor 2; IDFS, invasive disease-free survival; pCR, pathological complete response.

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