caa a22 4500 605490554 CHVBK 20210128100505.0 cr unu---uuuuu 210128e20151201xx s 000 0 eng 10.1007/s10147-015-0832-5 doi (NATIONALLICENCE)springer-10.1007/s10147-015-0832-5 Safety, pharmacokinetics and efficacy findings in an open-label, single-arm study of weekly paclitaxel plus lapatinib as first-line therapy for Japanese women with HER2-positive metastatic breast cancer [Elektronische Daten] [Kenichi Inoue, Katsumasa Kuroi, Satoru Shimizu, Yoshiaki Rai, Kenjiro Aogi, Norikazu Masuda, Takahiro Nakayama, Hiroji Iwata, Yuichiro Nishimura, Alison Armour, Yasutsuna Sasaki] Background: Lapatinib is the human epidermal growth factor receptor 2 (HER2) targeting agent approved globally for HER2-positive metastatic breast cancer (MBC). The efficacy, safety and pharmacokinetics (PK) of lapatinib combined with paclitaxel (L+P) were investigated in this study, to establish clear evidence regarding the combination in Japanese patients. Methods: In this two-part, single-arm, open-label study, the tolerability of L+P as first-line treatment in Japanese patients with HER2-positive MBC was evaluated in six patients in the first part, and the safety, efficacy and PK were evaluated in a further six patients (making a total of twelve patients) in the second part. Eligible women were enrolled and received lapatinib 1500mg once daily and paclitaxel 80mg/m2 weekly for at least 6 cycles. Results: The only dose-limiting toxicity reported was Grade 3 diarrhea in one patient. The systemic exposure to maximum plasma concentration and area under the plasma concentration curve (AUC) for lapatinib, as well as the AUC of paclitaxel, were increased when combined. The most common adverse events (AEs) related to the study treatment were alopecia, diarrhea and decreased hemoglobin. The majority of drug-related AEs were Grade 1 or 2. The median overall survival was 35.6months (95% confidence interval 23.9, not reached). The response rate and clinical benefit rate were both 83% (95% confidence interval 51.6, 97.9). Conclusions: The L+P treatment was well tolerated in Japanese patients with HER2-positive MBC. Although the PK profiles of lapatinib and paclitaxel influenced each other, the magnitudes were not greatly different from those in non-Japanese patients. The Author(s), 2015 Lapatinib nationallicence Paclitaxel nationallicence HER2 nationallicence Metastatic breast cancer nationallicence Inoue Kenichi Division of Breast Oncology, Saitama Cancer Center, 780 Komuro, Ina-machi, Kita-adachi-gun, 362-0806, Saitama, Japan aut Kuroi Katsumasa Department of Breast Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan aut Shimizu Satoru Department of Breast Oncology and Endocrine Surgery, Kanagawa Cancer Center, Yokohama, Kanagawa, Japan aut Rai Yoshiaki Hakuaikai Medical Corporation, Sagara Hospital, Kagoshima, Japan aut Aogi Kenjiro Department of Surgery, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan aut Masuda Norikazu Department of Surgery, Breast Oncology, National Hospital Organization Osaka National Hospital, Osaka, Japan aut Nakayama Takahiro Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Osaka, Japan aut Iwata Hiroji Department of Breast Oncology, Aichi Cancer Center Hospital, Nagoya, Japan aut Nishimura Yuichiro Development and Medical Affairs Division, GlaxoSmithKline K.K., Tokyo, Japan aut Armour Alison Research and Development, GlaxoSmithKline, Philadelphia, PA, USA aut Sasaki Yasutsuna Department of Medical Oncology, Saitama Medical University International Medical Center, Saitama, Japan aut International Journal of Clinical Oncology Springer Japan 20/6(2015-12-01), 1102-1109 1341-9625 20:6<1102 2015 20 10147 https://doi.org/10.1007/s10147-015-0832-5 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s10147-015-0832-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Inoue Kenichi Division of Breast Oncology, Saitama Cancer Center, 780 Komuro, Ina-machi, Kita-adachi-gun, 362-0806, Saitama, Japan aut NATIONALLICENCE 700 1- Kuroi Katsumasa Department of Breast Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan aut NATIONALLICENCE 700 1- Shimizu Satoru Department of Breast Oncology and Endocrine Surgery, Kanagawa Cancer Center, Yokohama, Kanagawa, Japan aut NATIONALLICENCE 700 1- Rai Yoshiaki Hakuaikai Medical Corporation, Sagara Hospital, Kagoshima, Japan aut NATIONALLICENCE 700 1- Aogi Kenjiro Department of Surgery, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan aut NATIONALLICENCE 700 1- Masuda Norikazu Department of Surgery, Breast Oncology, National Hospital Organization Osaka National Hospital, Osaka, Japan aut NATIONALLICENCE 700 1- Nakayama Takahiro Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Osaka, Japan aut NATIONALLICENCE 700 1- Iwata Hiroji Department of Breast Oncology, Aichi Cancer Center Hospital, Nagoya, Japan aut NATIONALLICENCE 700 1- Nishimura Yuichiro Development and Medical Affairs Division, GlaxoSmithKline K.K., Tokyo, Japan aut NATIONALLICENCE 700 1- Armour Alison Research and Development, GlaxoSmithKline, Philadelphia, PA, USA aut NATIONALLICENCE 700 1- Sasaki Yasutsuna Department of Medical Oncology, Saitama Medical University International Medical Center, Saitama, Japan aut NATIONALLICENCE 773 0- International Journal of Clinical Oncology Springer Japan 20/6(2015-12-01), 1102-1109 1341-9625 20:6<1102 2015 20 10147