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 |
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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 |
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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