A multicentre, international neoadjuvant (NA), randomized, double-blind phase III trial comparing fulvestrant to a combination of fulvestrant and palbociclib in patients with operable luminal breast cancer (SAFIA Trial)

Abstract

Background: NA chemotherapy (CT) +/‐anti‐Her2 treatment of operable breast cancer (BC) is considered a standard option in the management of BC. However, pathologic complete response (pCR) rates with CT in HR+/Her2‐BC are usually low: 7% (Luminal A) to 16% (Luminal B). Alternatively, NA endocrine therapy (ET) has not been established as a standard treatment because of low pCRs. Methods: This is a multicenter phase III, 3rd generation NA trial performed in 34 centers and 7 countries of Middle‐East and North Africa (MENA Region). The objective is to investigate the potential role of adding Palbociclib to ET (Fulvestrant +/‐Goserelin) compared to ET alone as NA therapy of HR+/Her2‐operable BC sensitive to ET. The primary endpoint is pCR with the hypothesis that the addition of Palbociclib would increase the pCR rate from 5% to 15%. Clinical/radiological response, conservative surgery rate, safety, disease���free and OS are secondary endpoints. Exploratory endpoints encompass biomarker serial analysis of liquid biopsies with Quantum Optic and DNA methylation technologies. Results: A total of 400 pre and post‐menopausal pts with stage II and IIIA are planned to be recruited. Oncotype DX is performed upfront in order to eliminate CT candidates. All pts with a recurrence score (RS) < 31 are treated with Fulvestrant (500 mg Day (d.) 1, 14, 28 then q. 28 d. (+/‐Goserelin 3.6 mg q.28 d.) for 4 months. Pts with responding/stable disease are then randomized in double blind fashion to Fulvestrant (+/‐Goserelin) with either Palbociclib 125mg po daily 3 weeks/4 or placebo. Four additional cycles are delivered before surgery The trial was initiated in 2018. As of April 2019, 196 patients have been enrolled. The majority of them (60%) are pre/peri menopausal. The mean age is 50.5 years (range: 25‐83). RS of<31 was reported in 75% of cases. So far, 96 pts have completed the induction ET and were randomized to ET with or without Palbociclib. End of accrual is expected by end of 2019. Conclusions: SAFIA trial aims to evaluate whether or not the addition of a CDK 4/6 inhibitor to pts sensitive to ET would validate a neo‐adjuvant strategy without CT in luminal operable BC.