Masahiro Kashiwaba1, Yoshinori Ito2, Shintaro Takao3, Hiroyoshi Doihara4, Yoshiaki Rai5, Kazumitsu Kanatani6, Shigemitsu Takashima7, Norikazu Masuda8. 1. Department of Surgery, Iwate Medical University School of Medicine, Morioka, Iwate nmasuda@alpha.ocn.ne.jp. 2. The Cancer Institute Hospital of JFCR, Koto-ku, Tokyo. 3. Hyogo Cancer Center, Akashi, Hyogo. 4. Okayama University Hospital, Okayama, Okayama. 5. Sagara Hospital, Kagoshima, Kagoshima. 6. Chugai Pharmaceutical Co. Ltd, Chuo-ku, Tokyo. 7. NHO Shikoku Cancer Center, Matsuyama, Ehime. 8. Department of Surgery, Breast Oncology, NHO Osaka National Hospital, Chuo-ku, Osaka, Japan.
Abstract
OBJECTIVE: Trastuzumab emtansine significantly improved progression-free survival and overall survival when compared with lapatinib-capecitabine in pretreated human epidermal growth factor receptor 2-positive advanced breast cancer. However, data in Japanese populations are limited. METHODS: In the single-arm Phase II JO22997 study, Japanese patients with human epidermal growth factor receptor 2-positive inoperable locally advanced/recurrent or metastatic breast cancer previously treated with at least one prior chemotherapy regimen for locally advanced/recurrent or metastatic breast cancer and trastuzumab in any setting received 3.6 mg/kg trastuzumab emtansine every 3 weeks until progression, unacceptable toxicity or consent withdrawal. The primary endpoint was Independent Review Committee-assessed objective response rate. Secondary endpoints included progression-free survival, overall survival, safety and pharmacokinetics. RESULTS: The objective response rate in 73 treated patients was 38.4% (90% confidence interval, 28.8-48.6%), exceeding the prespecified boundary for an objective response rate > 20%. After 6.5 months' median follow-up, median progression-free survival was 5.6 months (95% confidence interval, 4.6-8.2). After 28.9 months' median follow-up, median overall survival was 30.5 months (95% confidence interval 25.2-not reached). There were no treatment-related deaths. The most common Grade 3/4 adverse events were thrombocytopenia (22%) and aspartate aminotransferase elevations (14%). Thrombocytopenia did not require platelet transfusion and typically recovered before the next cycle. There were no substantial differences in trastuzumab emtansine or trastuzumab pharmacokinetic parameters between this study and previous data from non-Japanese patients. CONCLUSIONS: JO22997 results suggest high activity of trastuzumab emtansine in Japanese patients, a safety profile consistent with previous studies in non-Japanese patients, no new safety signals and no evidence of pharmacokinetic differences between Japanese and non-Japanese populations. These results support trastuzumab emtansine therapy for Japanese patients with chemotherapy- and trastuzumab-pretreated human epidermal growth factor receptor 2-positive locally advanced/recurrent or metastatic breast cancer.
OBJECTIVE:Trastuzumab emtansine significantly improved progression-free survival and overall survival when compared with lapatinib-capecitabine in pretreated humanepidermal growth factor receptor 2-positive advanced breast cancer. However, data in Japanese populations are limited. METHODS: In the single-arm Phase II JO22997 study, Japanese patients with humanepidermal growth factor receptor 2-positive inoperable locally advanced/recurrent or metastatic breast cancer previously treated with at least one prior chemotherapy regimen for locally advanced/recurrent or metastatic breast cancer and trastuzumab in any setting received 3.6 mg/kg trastuzumab emtansine every 3 weeks until progression, unacceptable toxicity or consent withdrawal. The primary endpoint was Independent Review Committee-assessed objective response rate. Secondary endpoints included progression-free survival, overall survival, safety and pharmacokinetics. RESULTS: The objective response rate in 73 treated patients was 38.4% (90% confidence interval, 28.8-48.6%), exceeding the prespecified boundary for an objective response rate > 20%. After 6.5 months' median follow-up, median progression-free survival was 5.6 months (95% confidence interval, 4.6-8.2). After 28.9 months' median follow-up, median overall survival was 30.5 months (95% confidence interval 25.2-not reached). There were no treatment-related deaths. The most common Grade 3/4 adverse events were thrombocytopenia (22%) and aspartate aminotransferase elevations (14%). Thrombocytopenia did not require platelet transfusion and typically recovered before the next cycle. There were no substantial differences in trastuzumab emtansine or trastuzumab pharmacokinetic parameters between this study and previous data from non-Japanese patients. CONCLUSIONS: JO22997 results suggest high activity of trastuzumab emtansine in Japanese patients, a safety profile consistent with previous studies in non-Japanese patients, no new safety signals and no evidence of pharmacokinetic differences between Japanese and non-Japanese populations. These results support trastuzumab emtansine therapy for Japanese patients with chemotherapy- and trastuzumab-pretreated humanepidermal growth factor receptor 2-positive locally advanced/recurrent or metastatic breast cancer.
Authors: William D Hedrich; Tamer E Fandy; Hossam M Ashour; Hongbing Wang; Hazem E Hassan Journal: Clin Pharmacokinet Date: 2018-06 Impact factor: 6.447