TY - JOUR
T1 - Trastuzumab Emtansine (T-DM1) Plus S-1 in Patients with Trastuzumab-Pretreated HER2-Positive Advanced or Metastatic Breast Cancer
T2 - A Phase Ib Study
AU - Kojima, Yasuyuki
AU - Yoshie, Reiko
AU - Kawamoto, Hisanori
AU - Shimo, Arata
AU - Uejima, Tomoko
AU - Iwatani, Tsuguo
AU - Motoyoshi, Ai
AU - Kanemaki, Yoshihide
AU - Boku, Narikazu
AU - Tsugawa, Koichiro
N1 - Funding Information:
The authors would like to thank all the patients who participated in this trial, as well as their families. We are also very appreciative of the staff at the Division of Breast and Endocrine Surgery, Department of Surgery. We also acknowledge support from Masaki Takahashi, Medical Informatics, St. Marianna University School of Medicine, for statistical analysis, and the support of the clinical research datacenter of St. Marianna University School of Medicine.
Publisher Copyright:
© 2019 S. Karger AG, Basel.
PY - 2019/6/1
Y1 - 2019/6/1
N2 - Background: In treating human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer, the efficacy of capecitabine combined with HER2-directed agents such as trastuzumab and lapatinib is supported by some evidence. The combination of T-DM1 and S-1, another oral 5-FU, may be a safe alternative treatment for metastatic breast cancer. Objectives: The optimal dose of S-1 was evaluated in combination with T-DM1 for patients with HER2-positive advanced or metastatic breast cancer. The safety and clinical response of this combination treatment were also assessed. Methods: This 3 + 3 dose-escalation study of S-1 given for the first 2 of 3 weeks, in combination with T-DM1 (3.6 mg/kg given every 3 weeks) to patients with trastuzumab-pretreated HER2-positive advanced or metastatic breast cancer was designed to evaluate the dose-limiting toxicity (DLT) occurrence in the first cycle. We also evaluated the safety and clinical activity of this combination treatment in multiple cycles. Two different dose levels of S-1 (65 and 80 mg/m2/day) were planned, although the capecitabine arm was abandoned because of slow recruitment. Results: Twelve out of the 13 patients enrolled were evaluable for DLT. One DLT (grade ≥3 non-hematological adverse events) occurred at dose level 0, leading to the expansion of this cohort to 6 patients, with an additional DLT (≥7 days discontinuation of medication), while no DLT occurred at dose level 1. As a result, the maximum tolerable dose of S-1 was determined to be 80 mg/m2/day for 14 days with T-DM1 3.6 mg/kg, repeated every 3 weeks. Two patients had grade 3 thrombocytopenia at dose level 0, and 1 patient at dose level 1. Conclusions: S-1 can be safely combined with the clinically relevant dose of T-DM1 in patients with HER2-positive advanced or metastatic breast cancer. Further evaluation with a larger sample size is required for efficacy assessment.
AB - Background: In treating human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer, the efficacy of capecitabine combined with HER2-directed agents such as trastuzumab and lapatinib is supported by some evidence. The combination of T-DM1 and S-1, another oral 5-FU, may be a safe alternative treatment for metastatic breast cancer. Objectives: The optimal dose of S-1 was evaluated in combination with T-DM1 for patients with HER2-positive advanced or metastatic breast cancer. The safety and clinical response of this combination treatment were also assessed. Methods: This 3 + 3 dose-escalation study of S-1 given for the first 2 of 3 weeks, in combination with T-DM1 (3.6 mg/kg given every 3 weeks) to patients with trastuzumab-pretreated HER2-positive advanced or metastatic breast cancer was designed to evaluate the dose-limiting toxicity (DLT) occurrence in the first cycle. We also evaluated the safety and clinical activity of this combination treatment in multiple cycles. Two different dose levels of S-1 (65 and 80 mg/m2/day) were planned, although the capecitabine arm was abandoned because of slow recruitment. Results: Twelve out of the 13 patients enrolled were evaluable for DLT. One DLT (grade ≥3 non-hematological adverse events) occurred at dose level 0, leading to the expansion of this cohort to 6 patients, with an additional DLT (≥7 days discontinuation of medication), while no DLT occurred at dose level 1. As a result, the maximum tolerable dose of S-1 was determined to be 80 mg/m2/day for 14 days with T-DM1 3.6 mg/kg, repeated every 3 weeks. Two patients had grade 3 thrombocytopenia at dose level 0, and 1 patient at dose level 1. Conclusions: S-1 can be safely combined with the clinically relevant dose of T-DM1 in patients with HER2-positive advanced or metastatic breast cancer. Further evaluation with a larger sample size is required for efficacy assessment.
KW - Chemotherapy
KW - Human epidermal growth factor receptor 2
KW - Metastatic breast cancer
KW - Phase Istudy
KW - S-1
UR - http://www.scopus.com/inward/record.url?scp=85063523569&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85063523569&partnerID=8YFLogxK
U2 - 10.1159/000497276
DO - 10.1159/000497276
M3 - Article
C2 - 30893699
AN - SCOPUS:85063523569
SN - 0030-2414
VL - 96
SP - 309
EP - 317
JO - Oncology
JF - Oncology
IS - 6
ER -
