Potential of afatinib in the treatment of patients with HER2-positive breast cancer

Figures & data

Figure 1 HER family receptors and some therapeutic agents available or in development.

Notes: HER2 forms homo- and heterodimers with other members of the EGFR family (HER1, HER3 and HER4). Dimerization activates multiple downstream signaling cascades including the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) pathways which promote cellular proliferation, survival, migration and invasion. Trastuzumab represents the first milestone of drugs targeting HER2 as individual receptor. Dual-targeting agents include monoclonal antibodies (Pertuzumab and TDM-1) and small molecule tyrosine kinase inhibitors (Lapatinib, Neratinib, Afatinib).

Table 1 Afatinib activity in breast cancer: main studies

Authors	N° patients	Study design	Key clinical results
Hickish et al^Citation22	41	Phase 2: patients with stage IIIb or IV breast cancer progressed on trastuzumab treated with afatinib 50 mg/day monotherapy	11% PR; 43% SD AE: diarrhea (24%) and skin rash (10%) G3
Harbeck et al^Citation24	56	Phase 2: patients with HER2 negative hormone receptor positive or triple negative, metastatic breast cancer progressed on no more than two chemotherapies, treated with afatinib 50 mg/day monotherapy	No ORR PFS: 54 days for the HER2 negative and hormone receptor positive group; 52 days for the triple negative group AE: manageable
Gunzer et al^Citation26	30	Phase 2: patients with stage IIIb or IV breast cancer progressed on letrozole, treated with the combination of letrozole plus afatinib	25% SD (for more than 16 weeks) AE: manageable

Abbreviations: PR, partial response; SD: stable disease; AE, adverse event; G, grade; ORR, overall response rate; PFS, progression free survival.

Table 2 Main ongoing clinical trials

Trial name (identifier)	Phase and status	Treatment scheme	Patient population
NCT01125566 (LUX Breast 1)	Phase 3: recruiting	Vinorelbine + trastuzumab vs vinorelbine + afatinib	I and II line metastatic breast cancer patients
NCT01325428	Phase 2: recruiting	Afatinib alone or in combination with vinorelbine	HER2 positive locally advanced or metastatic inflammatory breast cancer
NCT01441596 (LUX Breast 3)	Phase 2: recruiting	Afatinib alone or in combination with vinorelbine	HER2 positive breast cancer with brain metastasis after trastuzumab/lapatinib therapy
NCT00826267	Phase 2: completed	Afatinib monotherapy vs trastuzumab vs lapatinib	HER2 positive treatment-naïve stage IIIa breast cancer patients (neoadjuvant setting)
NCT00708214	Phase 2: completed	Afatinib in combination with letrozole	Hormone resistant metastatic breast cancer patients
NCT00425854	Phase 2: completed	Afatinib in monotherapy	HER2 negative metastatic breast cancer, after maximum 2 lines of chemotherapy
NCT00950742	Phase 1: active, not recruiting	Afatinib in combination with trastuzumab	HER2 positive advanced refractory breast cancer patients

HickishTUse of BIBW2992, a novel irreversible EGFR/HER1 and HER2 tyrosine kinase inhibitor to treat patients with HER2-positive metastatic breast cancer after failure of treatment with trastuzumabCancer Res20096924 Suppl Abstract nr 5060

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HarbeckNBIBW2992, a novel irreversible EGFR/HER1 and HER2 tyrosine kinase inhibitor for the treatment of patients with HER2-negative metastatic breast cancer after failure of no more than two prior chemotherapiesCancer Res20096924 Suppl Abstract nr 5062

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GunzerKAddition of BIBW 2992, an irreversible inhibitor of EGFR/HER1 and HER2, to letrozole in estrogen receptor (ER)-positive metastatic breast cancer (mBC) progressing on letrozole monotherapyJ Clin Oncol2815s2010suppl abstr 1072

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