The postoperative combination of S-1, an oral fluoropyrimidine-based drug, with endocrine therapy improved invasive disease–free survival and 5-year invasive disease–free survival estimates in patients with hormone receptor (HR)-positive, HER2-negative breast cancer, according to results from the phase III POTENT trial presented by Toi et al at the 2019 San Antonio Breast Cancer Symposium (Abstract GS1-09).
S-1 is a combination drug composed of tegafur—a fluorouracil prodrug that inhibits DNA synthesis and cell division—and gimeracil and oteracil, which promote tegafur activity and prevent gastrointestinal toxicity, respectively. Previous studies suggested that combining tegafur with endocrine therapy could improve antitumor efficacy.
“Although we have made remarkable progress with systemic therapy for breast cancer, many patients still experience disease recurrence,” said first author Masakazu Toi, MD, PhD, Professor of Breast Surgery at Kyoto University Hospital, in a statement.
Patients with HR-positive, HER2-negative breast cancer are often treated with endocrine therapies. Although this breast cancer subtype is associated with a favorable 5-year relative survival rate, there is a risk of disease recurrence several years after treatment, explained Dr. Toi. “Because of the risk of recurrence, there is interest in identifying novel postoperative adjuvant therapies to be used in conjunction with endocrine therapy,” he said.
In this study, Dr. Toi and colleagues examined the efficacy of S-1 in combination with adjuvant endocrine therapy in patients. The study enrolled 1,939 patients with stage I to III HR-positive, HER2-negative breast cancer with intermediate or higher risk of recurrence in the full analysis set. The study included patients from 139 centers in Japan. Patients were randomly assigned 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 (invasive disease–free survival events), compared to 155 of the 973 patients in the control arm (10.6 % vs 15.9%). The estimated 5-year invasive disease–free survival was 86.9% for patients in the S-1 arm compared to 81.6% in the control arm.
“We found that the postoperative adjuvant use of S-1 in combination with standard endocrine therapy significantly reduced [invasive disease–free survival] events and improved 5-year [invasive disease–free survival] estimates in patients with HR-positive, HER2-negative breast cancer,” said Dr. Toi. Furthermore, the S-1 treatment was well tolerated and manageable. Major toxicities associated with S-1 treatment included signs of bone marrow suppression, such as decreased neutrophil counts; gastrointestinal toxicities, such as nausea and diarrhea; hyperpigmentation; and fatigue.
“Our findings support the addition of S-1 to standard endocrine therapy in the postoperative adjuvant setting for patients with HR-positive, HER2-negative disease and an intermediate or higher risk of recurrence,” said Dr. Toi.
A limitation of the study is that it only included patients from Japan, and the toxicity profile may be slightly different between Asian and non-Asian patients, said researchers.
Disclosure: The study was sponsored by the Comprehensive Support Project of the Public Health Research Foundation and Taiho Pharmaceutical. For full disclosures of the study authors, visit abstractsonline.com.
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