Toshimi Takano1, Junji Tsurutani2, Masato Takahashi3, Takeharu Yamanaka4, Kazuko Sakai5, Yoshinori Ito6, Junya Fukuoka7, Hideharu Kimura8, Hidetaka Kawabata9, Kenji Tamura10, Koji Matsumoto11, Kenjiro Aogi12, Kazuhiko Sato13, Kazuto Nishio5, Kazuhiko Nakagawa2, Toshiaki Saeki14. 1. Department of Medical Oncology, Toranomon Hospital, Tokyo, Japan. Electronic address: takano@toranomon.gr.jp. 2. Department of Medical Oncology, Kindai University, Osaka, Japan. 3. Department of Breast Surgery, NHO Hokkaido Cancer Center, Hokkaido, Japan. 4. Department of Biostatistics, Yokohama City University, Kanagawa, Japan. 5. Department of Genome Biology, Kindai University, Osaka, Japan. 6. Department of Breast Medical Oncology, Cancer Institute Hospital, Tokyo, Japan. 7. Department of Pathology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. 8. Hematology/Respiratory Medicine, Kanazawa University Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Ishikawa, Japan. 9. Department of Breast and Endocrine Surgery, Toranomon Hospital, Tokyo, Japan. 10. Department of Breast and Medical Oncology, National Cancer Center Hospital, Tokyo, Japan. 11. Department of Medical Oncology, Hyogo Cancer Center, Hyogo, Japan. 12. Department of Breast Oncology, Shikoku Cancer Center, Ehime, Japan. 13. Department of Breast Oncology, Tokyo-West Tokushukai Hospital, Tokyo, Japan. 14. Department of Breast Oncology, Saitama Medical University International Medical Center, Saitama, Japan.
Abstract
BACKGROUND: For human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) with progression on trastuzumab-based therapy, continuing trastuzumab beyond progression and switching to lapatinib combined with chemotherapy are both valid options. We conducted an open-label, randomized phase II trial to compare the efficacy of these strategies. PATIENTS AND METHODS: Women with HER2-positive MBC previously treated withtrastuzumab and taxanes were randomly assigned to receive trastuzumab plus capecitabine (HX) or lapatinib plus capecitabine (LX). The primary endpoint was progression-free survival (PFS) and the secondary endpoints included overall survival (OS) and the objective response rate (ORR). To explore the predictive value of the differential benefit of anti-HER2 drugs, PIK3CA mutations were assessed using circulating tumor DNA. RESULTS:Eighty-six patients (43 in each arm) were enrolled. The median PFS was 6.1 months in the HX arm and 7.1 months in the LX arm (hazard ratio, 0.81; 90% CI, 0.55-1.21; p = 0.39); the median OS was 31.0 months in the HX arm and was not reached in the LX arm (hazard ratio, 0.58; 95% CI, 0.26-1.31; p = 0.18). The ORR was 40% in the HX arm and 41% in the LX arm. PIK3CA mutations were detected in 23% of the 35 analyzed patients, and in patients without PIK3CA mutations, LX yielded relatively longer PFS and OS than HX. CONCLUSION: In women with HER2-positive MBC previously treated withtrastuzumab and taxanes, no significant differences in PFS and OS were observed between patients treated with LX and HX. TRIAL REGISTRATION NUMBER: UMIN000005219.
RCT Entities:
BACKGROUND: For humanepidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) with progression on trastuzumab-based therapy, continuing trastuzumab beyond progression and switching to lapatinib combined with chemotherapy are both valid options. We conducted an open-label, randomized phase II trial to compare the efficacy of these strategies. PATIENTS AND METHODS: Women with HER2-positive MBC previously treated with trastuzumab and taxanes were randomly assigned to receive trastuzumab plus capecitabine (HX) or lapatinib plus capecitabine (LX). The primary endpoint was progression-free survival (PFS) and the secondary endpoints included overall survival (OS) and the objective response rate (ORR). To explore the predictive value of the differential benefit of anti-HER2 drugs, PIK3CA mutations were assessed using circulating tumor DNA. RESULTS: Eighty-six patients (43 in each arm) were enrolled. The median PFS was 6.1 months in the HX arm and 7.1 months in the LX arm (hazard ratio, 0.81; 90% CI, 0.55-1.21; p = 0.39); the median OS was 31.0 months in the HX arm and was not reached in the LX arm (hazard ratio, 0.58; 95% CI, 0.26-1.31; p = 0.18). The ORR was 40% in the HX arm and 41% in the LX arm. PIK3CA mutations were detected in 23% of the 35 analyzed patients, and in patients without PIK3CA mutations, LX yielded relatively longer PFS and OS than HX. CONCLUSION: In women with HER2-positive MBC previously treated with trastuzumab and taxanes, no significant differences in PFS and OS were observed between patients treated with LX and HX. TRIAL REGISTRATION NUMBER: UMIN000005219.
Authors: G Nader-Marta; D Martins-Branco; E Agostinetto; M Bruzzone; M Ceppi; L Danielli; M Lambertini; N Kotecki; A Awada; E de Azambuja Journal: ESMO Open Date: 2022-05-30
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