Front-Line S-1 ‘Non-Inferior’ To Taxanes For Select HER2-Negative Metastatic Breast Cancers

Oral fluoropyrimidine shows non-inferiority to first-line taxane-based chemotherapy for select patients with metastatic breast cancer

medwireNews: The combination oral fluoropyrimidineagent S-1 may offer an alternative first-line treatment for patients with human epidermal growth factor receptor (HER)2-negative metastatic breast cancer, Japanese open-label, phase III results suggest.

The SELECT BC trial found that S-1 – composed of a modified form of fluorouracil plus tegafur, gimeracil and oteracil – was non-inferior to taxane-based regimens in terms of median overall survival, at 35.0 versus 37.2 months.

And although S-1 was associated with a higher rate of grade 3 or worse neutropenia (7 vs 3%) than taxane chemotherapy, S-1-treated patients had comparable rates of fatigue (3 vs 4%) and were less likely to experience oedema (<1 vs 4%).

Moreover, the S-1 regimen was associated with a significantly better global health status than taxane-based chemotherapy, with gains in all five domains of physical, role, emotional, cognitive and social functioning.

“Our study not only provides scientific evidence to support the use of an oral fluoropyrimidine as first-line chemotherapy, but also satisfies the need for patient choice of treatment”, say Hirofumi Mukai, from the National Cancer Center Hospital East in Kashiwa-shi, Japan, and co-investigators.

They add in The Lancet Oncology that a second trial, SELECT BC-CONFIRM, comparing S-1 first-line treatment for metastatic breast cancer with anthracycline-based chemotherapy regimens is now underway.

The SELECT BC trial included 307 patients with endocrine-resistant tumours who were randomly assigned to receive first-line treatment for advanced disease with S-1 (40–60 mg twice daily for 28 days, 2-week break), while 286 patients received docetaxel (60–75 mg/m2 every 3–4 weeks), weekly paclitaxel (80–100 mg/m2 for 3–4 weeks) or paclitaxel (175 mg/m2 every 3–4 weeks)).

In an accompanying comment, Miguel Martin and Sara Lopez-Tarruella, from Universidad Complutense in Madrid, Spain, describe the trial as “high quality” with regard to design, conduct and credibility and note the “acceptable” non-inferiority margin of 1.333.

However, they note that the study included both patients with endocrine-resistant, hormone receptor-positive breast cancer and those with triple-negative disease and that subanalysis found S-1 to be non-inferior to taxane treatment only for the former patients. The hazard ratio (HR) for overall survival for triple-negative patients was 1.29 in favour of paclitaxel or docetaxel treatment.

“This difference raises concerns about how much the non-inferiority of S-1 in the overall population can be extrapolated to patients with triple-negative breast cancer”, the commentators write.

They also note that the subanalysis supported non-inferiority of S-1 in patients without liver metastasis but the HR for overall survival favoured taxanes for those with liver metastasis, “calling into question the applicability of the overall conclusions of the trial to patients with liver metastases.”

Nevertheless, Miguel Martin and Sara Lopez-Tarruella conclude: “Despite these concerns, the SELECT BC trial provides strong evidence that patients with endocrine-resistant hormone receptor-positive HER2-negative metastatic breast cancer (without substantial liver involvement or life-threatening metastases) can be treated with a first-line oral fluoropyrimidine (S-1) without any detrimental effect on survival while avoiding the toxic effects of intravenous chemotherapy and maintaining a good quality of life.”


Takashima T, Mukai H, Hara F, et al. Taxanes versus S-1 as the first-line chemotherapy for metastatic breast cancer (SELECT BC): an open-label, non-inferiority, randomised phase 3 trial. Lancet Oncol 2015; Advance online publication 23 November. DOI:

Martin M, Lopez-Tarruella S. S1 versus taxanes for HER2-negative metastatic breast cancer. Lancet Oncol 2015; Advance online publication 23 November. DOI:

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