title: A multicenter Phase II study evaluating the efficacy, safety and pharmacokinetics of trastuzumab emtansine in Japanese patients with heavily pretreated HER2-positive locally recurrent or metastatic breast cancer.
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.
authors.affiliation: Department of Surgery, Iwate Medical University School of Medicine, Morioka, Iwate nmasuda@alpha.ocn.ne.jp.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kashiwaba
authors.affiliation: The Cancer Institute Hospital of JFCR, Koto-ku, Tokyo.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Hyogo Cancer Center, Akashi, Hyogo.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Takao
authors.affiliation: Okayama University Hospital, Okayama, Okayama.
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Doihara
authors.affiliation: Sagara Hospital, Kagoshima, Kagoshima.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Rai
authors.affiliation: Chugai Pharmaceutical Co. Ltd, Chuo-ku, Tokyo.
authors.forename: Kazumitsu
authors.initials: K
authors.lastname: Kanatani
authors.affiliation: NHO Shikoku Cancer Center, Matsuyama, Ehime.
authors.forename: Shigemitsu
authors.initials: S
authors.lastname: Takashima
authors.affiliation: Department of Surgery, Breast Oncology, NHO Osaka National Hospital, Chuo-ku, Osaka, Japan.
authors.forename: Norikazu
authors.initials: N
authors.lastname: Masuda
mesh_terms: D000080044:Ado-Trastuzumab Emtansine; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D044466:Asian People; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006207:Half-Life; D006801:Humans; D007564:Japan; D008453:Maytansine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D015996:Survival Rate; D013921:Thrombocytopenia / Q000209:etiology; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D000080044:Ado-Trastuzumab Emtansine; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D008453:Maytansine; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab
keywords: HER2-positive; Japanese; T-DM1; antibody–drug conjugate (ADC); metastatic breast cancer; trastuzumab emtansine