228P Fulvestrant with additional palbociclib in advanced or metastatic hormone receptor-positive HER2-negative breast cancer after progression to fulvestrant monotherapy: JBCRG- M07 (FUTURE trial)

Abstract

Fulvestrant is one of the standard treatments for first- or second-line endocrine therapy for hormone receptor (HR)-positive metastatic breast cancer (MBC). We investigated whether the addition of palbociclib to fulvestrant was effective and safe in patients with HR-positive MBC and advanced breast cancer (ABC) who relapsed with fulvestrant monotherapy. Patients were primary registered during fulvestrant treatment as 1st or 2nd endocrine therapy. Patients were secondary registered when patients had disease progression during fulvestrant monotherapy and received fulvestrant and palbociclib as the study treatment. The primary endpoint was progression free survival(PFS) from the start of the study treatment. The secondary endpoints included the time to treatment failure(TTF) from the start of the study treatment and adverse events. Our null hypothesis was a median PFS of 5 months, which was the value reported in the PALOMA 3 study. Assuming the median PFS of 8 months for the alternative hypothesis, 63 patients were required to reject the null hypothesis with 80% power under a one-sided alpha of 0.05. (UMIN 000029294). Between January, 2018 and February, 2020, we enrolled 167 patients from 55 institutions as 1st registration. However, nine cases were excluded from analysis for not meeting inclusion criteria. Of these, 72 patients were enrolled in 2ndary registration. Median follow up time were 23.8 months from 1st registration and 8.9 months from 2nd registration. Median PFS of the study treatment in patients with resistance to fulvestrant monotherapy was 9.4 months (90% Confidence interval 6.9- 11.2 months, p<0.001). TTF from 2nd registration was 7.2 months (90% CI 5.5- 10.4 months). No new adverse events were observed. Our data suggest that palbociclib plus fulvestrant beyond disease progression to fulvestrant monotherapy is possibly effective and safe in patients with HR-positive HER2-negative ABC/MBC.