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

Autor: Javier Garcia-Corbacho, James Spicer, Jacques Bonneterre, Iain R. Macpherson, Pavlina Spiliopoulou, Mario Campone, Saeed Rafii, Richard D. Baird, J Posner, Matilde Saggese, Antoine Italiano, Yousuke Takeda, A Arimura, Nicola Cresti
Přispěvatelé: Baird, Richard [0000-0001-7071-6483], Apollo - University of Cambridge Repository
Rok vydání: 2019
Předmět:
Oncology
Male
Receptor
ErbB-2
medicine.medical_treatment
PROGRESSION
0302 clinical medicine
Trastuzumab
Antineoplastic Combined Chemotherapy Protocols
skin and connective tissue diseases
0303 health sciences
Brain Neoplasms
Vinorelbine
Middle Aged
OPEN-LABEL
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Metastatic breast cancer
Treatment Outcome
Tolerability
030220 oncology & carcinogenesis
Female
TYROSINE KINASE INHIBITOR
Life Sciences & Biomedicine
medicine.drug
Research Article
Adult
medicine.medical_specialty
EGFR
Breast Neoplasms
Epertinib
lcsh:RC254-282
TBCRC 022
Drug Administration Schedule
II TRIAL
Capecitabine
03 medical and health sciences
Breast cancer
LAPATINIB
Internal medicine
HER2
medicine
Humans
1112 Oncology and Carcinogenesis
Oncology & Carcinogenesis
Adverse effect
HER2-positive breast cancer
neoplasms
030304 developmental biology
Aged
Chemotherapy
Science & Technology
Dose-Response Relationship
Drug
business.industry
NERATINIB
PERTUZUMAB
medicine.disease
Quinazolines
GROWTH-FACTOR RECEPTOR
business
Zdroj: MacPherson, I R, Spiliopoulou, P, Rafii, S, Saggese, M, Baird, R D, Garcia-Corbacho, J, Italiano, A, Bonneterre, J, Campone, M, Cresti, N, Posner, J, Takeda, Y, Arimura, A & Spicer, J 2019, ' A phase I/II study of epertinib plus trastuzumab with or without chemotherapy in patients with HER2-positive metastatic breast cancer ', Breast Cancer Research, vol. 22, 1 . https://doi.org/10.1186/s13058-019-1178-0
Breast Cancer Research : BCR
Breast Cancer Research, Vol 22, Iss 1, Pp 1-9 (2019)
ISSN: 1465-5411
DOI: 10.1186/s13058-019-1178-0
Popis: Background Epertinib (S-222611) is a potent reversible inhibitor of HER2, EGFR and HER4. This trial evaluated the safety, tolerability, pharmacokinetics and antitumour activity of daily oral epertinib combined with trastuzumab (arm A), with trastuzumab plus vinorelbine (arm B) or with trastuzumab plus capecitabine (arm C), in patients with HER2-positive metastatic breast cancer (MBC). Methods Eligible patients, with or without brain metastases, had received prior HER2-directed therapy. A dose-escalation phase determined the tolerability of each combination and established a dose for further study. Further, patients were recruited to expansion cohorts in each of the 3 arms to further explore efficacy and safety. Results The recommended doses of epertinib were 600 mg, 200 mg and 400 mg in arms A, B and C, respectively. The most frequent grade 3/4 adverse event (AE) was diarrhoea in all arms, which was manageable with medical intervention and dose modification. The objective response rate (complete response [CR] plus partial response [PR]) in heavily pre-treated HER2-positive MBC patients at the recommended doses of epertinib combined with trastuzumab was 67% (N = 9), with trastuzumab plus vinorelbine was 0% (N = 5) and with trastuzumab plus capecitabine was 56% (N = 9). Notably, 4 of 6 patients previously treated with T-DM1 responded in the arm A expansion cohort (epertinib plus trastuzumab). In the arm C expansion cohort (epertinib plus trastuzumab plus capecitabine), 4 of 7 patients responded despite previous exposure to capecitabine. Measurable regression of brain metastases was observed in patients with CNS target lesions treated in both arms A and C. Conclusion We observed safety, tolerability and encouraging antitumour activity of epertinib combined with trastuzumab, or with trastuzumab plus capecitabine. This supports further evaluation of these combinations in patients with pre-treated HER2-positive MBC, with or without brain metastases. Trial registration EudraCT Number: 2013-003894-87; registered 09-September-2013.
Databáze: OpenAIRE
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