Adding S-1 Combo to Post-Op Endocrine Therapy Improves Outcomes for HR-Positive/HER2-Negative Breast Cancer


The study results were presented at the 2019 San Antonio Breast Cancer Symposium, held December 10 through 14.

Results of a phase 3 study have found that combining an oral fluoropyrimidine-based drug with post-operative endocrine therapy increased invasive disease-free survival (iDFS) and improved 5-year iDFS estimates in patients with hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer.

The study results were presented at the 2019 San Antonio Breast Cancer Symposium, held December 10 through 14.

Patients with HR-positive/HER2-negative breast cancer are often treated with endocrine therapies, which work to prevent hormones from activating cancer growth. Although HR-positive/HER2-negative breast cancer is associated with a favorable 5-year relative survival rate, disease recurrence is a risk several years after treatment.

“Because of the risk of recurrence, there is interest in identifying novel post-operative adjuvant therapies to be used in conjunction with endocrine therapy,” said Masakazu Toi, MD, PhD, professor of breast surgery at Kyoto University Hospital, in a statement.

Researchers have now found evidence that the combination therapy tegafur/gimeracil/oteracil (S-1) may lower rates of recurrence. Tegafur is a 5-fluororacil prodrug that inhibits DNA synthesis and cell division, whereas gimeracil and oteracil promote tegafur activity and prevent gastrointestinal activity, respectively. Previous studies have suggested that combining tegafur with endocrine therapy could improve anti-tumor efficacy, according to the authors of the current study.

The current study included 1939 patients with stage 1 to 3 HR-positive/HER2-negative breast cancer with intermediate or higher risk of recurrence in the full analysis set. Patients were randomized to receive either S-1 and endocrine therapy or endocrine therapy alone as adjuvant treatment.

The median follow-up after treatment was 51.4 months. Among the 957 patients in the S-1 arm, 101 experienced disease recurrence (10.6%), compared with 155 of the 973 patients in the control arm (15.9%). The estimated 5-year iDFS was 86.9% for patients in the S-1 arm compared with 81.6% in the control arm.

The S-1 treatment was well tolerated and manageable. Major toxicities associated with S-1 included signs of bone marrow suppression, gastrointestinal toxicities, hyperpigmentation, and fatigue.

“Our findings support the addition of S-1 to standard endocrine therapy in the post-operative adjuvant setting for patients with HR-positive/HER2-negative disease and an intermediate or higher risk of recurrence,” Toi said in a statement.


Addition of S-1 to Post-Operative Endocrine Therapy Improves Outcomes for Patients with hormone Receptor-positive, HER2-negative Breast Cancer [news release]. San Antonio, TX; released Dec 11, 2019. American Association for Cancer Research. Accessed Dec 5, 2019.

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