Hiroji Iwata1, Norikazu Masuda2, Daigo Yamamoto3, Yoshiaki Sagara4, Nobuaki Sato5, Yutaka Yamamoto6, Mitsue Saito7, Takashi Fujita8, Shoji Oura9, Junichiro Watanabe10, Masami Tsukabe11, Kazumi Horiguchi12, Satoshi Hattori13, Yoshimasa Matsuura14, Katsumasa Kuroi12. 1. Department of Breast Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan. hiwata@aichi-cc.jp. 2. Department of Surgery, Breast Oncology, National Hospital Organization Osaka National Hospital, Osaka, Japan. 3. Department of Surgery, Kansai Medical University Medical Center, Osaka, Japan. 4. Department of Breast Surgery, Sagara Hospital, Kagoshima, Japan. 5. Department of Surgery, Niigata Cancer Center Hospital, Niigata, Japan. 6. Department of Breast and Endocrine Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. 7. Department of Breast Oncology, Juntendo University Hospital, Tokyo, Japan. 8. Department of Breast Oncology, Jichi Medical University Hospital, Tochigi, Japan. 9. Department of Thoracic and Cardiovascular Surgery, Wakayama Medical University, Wakayama, Japan. 10. Department of Breast Oncology, Shizuoka Cancer Center, Shizuoka, Japan. 11. Department of Breast Surgery, NTT West Osaka Hospital, Osaka, Japan. 12. Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan. 13. Biostatistics Center, Kurume University, Fukuoka, Japan. 14. Medical Affairs, Chugai Pharmaceutical CO., LTD., Tokyo, Japan.
Abstract
PURPOSE: Prognostic effects of circulating tumor cells (CTCs) have been reported in metastatic breast cancer (MBC). However, few phase III trials have investigated the potential role of CTCs in treatment selection. We explored potential relationships between CTCs, efficacy, and differential treatment effects. METHODS:Patients with HER2-negative MBC were randomized to receive either concurrent capecitabine plus docetaxel (XT) or sequential single-agent docetaxel followed by single-agent capecitabine at progression (T → X). Blood samples were collected at baseline, on day 1 of cycles 2 and 3, and at progression. CTCs were counted using the CellSearch® System. The relationship between baseline CTC count and outcomes was investigated using a pre-defined threshold of 2 CTCs/7.5 mL. RESULTS: At screening, 44% of the 148 enrolled patients had positive CTC score. In multivariate analyses of pooled treatment arms, positive baseline CTC and triple-negative disease were strongly associated with worse progression-free survival (PFS) and overall survival (OS). Patients with positive CTC score at the baseline had worse OS, irrespective of change in CTC (decreased versus remaining positive) at cycle 2. The prognostic effect of baseline CTC count on OS appeared slightly less pronounced in XT-treated pts. compared with T → X. CONCLUSIONS: A baseline CTC count ≥2 CTCs/7.5 mL was associated with worse prognosis. However, some improvement in PFS and OS was shown with concurrent XT, thus baseline CTC could be a predictive marker. As the current trial was not designed to evaluate a change in chemotherapy according to on-treatment CTC changes, prospective investigation is required.
RCT Entities:
PURPOSE: Prognostic effects of circulating tumor cells (CTCs) have been reported in metastatic breast cancer (MBC). However, few phase III trials have investigated the potential role of CTCs in treatment selection. We explored potential relationships between CTCs, efficacy, and differential treatment effects. METHODS:Patients with HER2-negative MBC were randomized to receive either concurrent capecitabine plus docetaxel (XT) or sequential single-agent docetaxel followed by single-agent capecitabine at progression (T → X). Blood samples were collected at baseline, on day 1 of cycles 2 and 3, and at progression. CTCs were counted using the CellSearch® System. The relationship between baseline CTC count and outcomes was investigated using a pre-defined threshold of 2 CTCs/7.5 mL. RESULTS: At screening, 44% of the 148 enrolled patients had positive CTC score. In multivariate analyses of pooled treatment arms, positive baseline CTC and triple-negative disease were strongly associated with worse progression-free survival (PFS) and overall survival (OS). Patients with positive CTC score at the baseline had worse OS, irrespective of change in CTC (decreased versus remaining positive) at cycle 2. The prognostic effect of baseline CTC count on OS appeared slightly less pronounced in XT-treated pts. compared with T → X. CONCLUSIONS: A baseline CTC count ≥2 CTCs/7.5 mL was associated with worse prognosis. However, some improvement in PFS and OS was shown with concurrent XT, thus baseline CTC could be a predictive marker. As the current trial was not designed to evaluate a change in chemotherapy according to on-treatment CTC changes, prospective investigation is required.
Entities:
Keywords:
Circulating tumor cells; HER2-negative; Metastatic breast cancer; Phase III trial; Prognostic factor
Authors: Lorena Alexandra Lisencu; Sebastian Trancă; Eduard-Alexandru Bonci; Andrei Pașca; Carina Mihu; Alexandru Irimie; Oana Tudoran; Ovidiu Balacescu; Ioan Cosmin Lisencu Journal: Biomedicines Date: 2022-03-25
Authors: Sven Kruspe; David D Dickey; Kevin T Urak; Giselle N Blanco; Matthew J Miller; Karen C Clark; Elliot Burghardt; Wade R Gutierrez; Sneha D Phadke; Sukriti Kamboj; Timothy Ginader; Brian J Smith; Sarah K Grimm; James Schappet; Howard Ozer; Alexandra Thomas; James O McNamara; Carlos H Chan; Paloma H Giangrande Journal: Mol Ther Nucleic Acids Date: 2017-08-12 Impact factor: 8.886