A phase II, randomized, open-label, dose-finding study of TAS-108, a novel steroidal antiestrogen, administered orally in postmenopausal women with advanced or metastatic breast cancer.
Authors: H Iwata, H Inaji, T Nakayama, N Yamamoto, S Noguchi, T Ikeda
Journal: Cancer Research (2009)

Abstract Abstract #2132 Background: A phase II study was conducted to identify the recommended dose of TAS-108, a novel steroidal antiestrogen with full ERα antagonist, mainly metabolized by CYP3A4, in post menopausal Japanese women with advanced or metastatic breast cancer. This study was prepared referring to the multi-center phase II trial that performed in four countries (USA, Russia, Mexico and Chile), and performed in Japan. Both studies are not the same designs.&amp;#x2028; Patients and Methods: Patients with ER and/or PgR positive were eligible if they had one or two standard endocrine therapies, with or without one prior chemotherapy, for advanced disease. TAS-108 was administered orally at three different doses (40mg/80mg/120mg per day) for 24 weeks. The treatment was terminated if PD was observed. In this clinical study, clinical benefit (CB, CR+PR+SD for at least 24 weeks) rate as the primary end point was evaluated. The secondary endpoints were overall response rate and best overall response using RECIST; time to progression; adverse events (AEs) graded by CTC-AE (ver.3.0). Endometrial thickness (ET) and bone mineral density (BMD) as specific items of hormonal therapy were evaluated by transvaginal or transabdominal ultrasound, and dual-energy X-Ray absorptiometry method, respectively.&amp;#x2028; Results: Ninety eight patients were enrolled and randomized. One ineligible patient in the 120mg dose group dropped out without administration; therefore a total of ninety seven patients were administered and assessed for efficacy and safety. Thirty three patients received 40mg, 32 received 80mg and 120mg. The three treatment groups were well balanced. CB was observed in 10 patients (30.3%) in the 40mg group, and 8 patients (25.0%) in both the 80mg and 120mg groups. Retrospective analysis showed TAS-108 had effectiveness to patients who had failed on prior tamoxifen (TAM) or aromatase inhibitors (AI) treatment, including relapse during the adjuvant therapy or within 6 months from its completion. CB rate at the three doses respectively were 25.0/33.3/25.0% in 14 (4/6/4) patients failed on TAM, and 30.8/31.6/20.0% in 70 (26/19/25) patients failed on AI.&amp;#x2028; TAS-108 was well tolerated and most of the AEs were Grade1 or 2. The most frequent drug-related AEs were hot flush (22 patients, 22.7%, 7/8/7 patients in 40/80/120mg), perspiration (11 patients, 11.3%, 2/3/6), nausea (9 patients, 9.3%, 1/3/5), arthralgia (6 patients, 6.2%, 0/3/3). Neither remarkable change nor apparent dose-related trend among the three groups was observed in ET or BMD.&amp;#x2028; Conclusion: According to the protocol, 40mg was chosen as the recommended dose of TAS-108 for breast cancer. It was suggested that TAS-108 has clinical benefit for patients with breast cancer who have failed on prior TAM or AI treatments. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2132.