A phase I/II study of epertinib plus trastuzumab with or without chemotherapy in patients with HER2-positive metastatic breast cancer

Background: Epertinib (S-222611) is really a potent reversible inhibitor of HER2, EGFR and HER4. This trial evaluated the security, tolerability, pharmacokinetics and antitumour activity of daily dental epertinib coupled with trastuzumab (arm A), with trastuzumab plus vinorelbine (arm B) or with trastuzumab plus capecitabine (arm C), in patients with HER2-positive metastatic cancer of the breast (MBC).

Methods: Qualified patients, without or with brain metastases, had received prior HER2-directed therapy. A serving-escalation phase determined the tolerability of every combination and established a serving for more study. Further, patients were employed to expansion cohorts in each one of the 3 arms to help explore effectiveness and safety.

Results: The suggested doses of epertinib were 600 mg, 200 mg and 400 mg in arms A, B and C, correspondingly. The commonest grade 3/4 adverse event (AE) was diarrhoea in most arms, that was manageable with medical intervention and dose modification. The aim response rate (complete response [CR] plus partial response [PR]) in heavily pre-treated HER2-positive MBC patients in the suggested doses of epertinib coupled with trastuzumab was 67% (N = 9), with trastuzumab plus vinorelbine was % (N = 5) with trastuzumab plus capecitabine was 56% (N = 9). Particularly, 4 of 6 patients formerly given T-DM1 responded within the arm A expansion cohort (epertinib plus trastuzumab). Within the arm C expansion cohort (epertinib plus trastuzumab plus capecitabine), 4 of seven patients responded despite previous contact with capecitabine. Measurable regression of brain metastases was noticed in patients with CNS target lesions treated both in arms A and C.

Conclusion: We observed safety, tolerability and inspiring antitumour activity of epertinib coupled with trastuzumab, or with trastuzumab plus capecitabine. This supports further look at these combinations in patients with pre-treated HER2-positive MBC, without or with brain metastases.