Pooled analysis of long-term outcome of patients enrolled in two trials comparing the efficacy of oral tegafur-uracil with CMF (N-SAS-BC01 and CUBC trials)

Background: Two randomized controlled trials comparing the efficacy of oral tegafur-uracil (UFT) (2 years) with that of classical cyclophosphamide, methotrexate, and fluorouracil (CMF) (6 courses) were conducted in patients with resected early breast cancer (N-SAS-BC01 trial [Watanabe et al, J Clin Oncol 2009] and CUBC trial [Park et al, Br J Cancer 2009]). Pooled analysis of these two randomized controlled trials using individual patient data has been published (Ohashi et al, Breast Cancer Res Treat 2010) and long-term follow-up data has also been reported (Yonemori et al, SABCS 2018). However, because the pathological factors evaluated in those studies are insufficient and based on old criteria, a re-evaluation using the current standard pathological factors is requited to use the data in the clinical practice. Methods: Paraffin-embedded sections of surgically excised tumor tissue were available for patients with resected stage I-IIIA breast cancer. The expression of estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) and the Ki67 labeling index were assessed by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), and the grades of TILs were evaluated by hematoxylin and eosin (HE UFT n=347). The median follow-up time was 11.1 years (12.1 years in the N-SAS-BC 01 trial and 8.3 years in the CUBC trial). Baseline characteristics were similar in each group. The 10-year RFS and OS was 79.9%, 87.7% in the CMF arm, and 77.1%, 88.8% in the UFT arm, respectively. The hazard ratio (UFT vs. CMF) was 0.962 (95% CI 0.712-1.300) for RFS and 0.929 (95% CI 0.639-1.350) for OS. Table 1 shows the 10-year RFS and OS in each IHC-defined breast cancer subtype. 10-year OS in UFT arm and in CMF arm were similar in Hormone receptor (HR) + groups. Although this is not expected, there is a positive signal of benefit of UFT in HR-HER2+ group (RFS; hazard ratio 0.296 (95% CI 0.100-0.878)). High TILs were associated with better prognosis in all patient group (vs. low TILs: hazard ratio 0.347 (95% CI 0.140-0.855)), however in HR+ HER2- group, there was no association between TIL status and prognosis (High vs. low: hazard ratio 0.787 (95% CI 0.240-2.581)). TILs status could not predict the benefit of UFT in the subset analysis of all patient group and of each subtype group. Conclusion: This long-term follow-up study using randomized controlled trials shows that RFS and OS are similar in luminal type patients treated with UFT and CMF. Funding: Taiho Pharmaceutical CO., LTD. Citation Format: Shigehira Saji, Shinji Ohno, Norikazu Masuda, Hitoshi Tsuda, Futoshi Akiyama, Masafumi Kurosumi, Akihiko Shimomura, Nobuaki Sato, Shintaro Takao, Shozo Ohsumi, Yutaka Tokuda, Hideo Inaji, Toru Watanabe, Yasuo Ohashi. Pooled analysis of long-term outcome of patients enrolled in two trials comparing the efficacy of oral tegafur-uracil with CMF (N-SAS-BC01 and CUBC trials) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-14-17.