Final result for SAFIA trial for neoadjuvant palbociclib in patients with operable luminal breast cancer responding to fulvestrant.

Abstract

596 Background: Luminal, human epidermal growth factor receptor 2 (HER2)-negative breast cancer (BC) encompasses the most common subtype of breast malignancies. Neoadjuvant strategies of operable BC are primarily based upon chemotherapy (CT), while neoadjuvant hormone therapy (NAHT) has not been well studied in the Middle East and North Africa (MENA) region. However, these tumors might respond poorly to neoadjuvant CT with significant side effects, emphasizing the need to identify patients who could be candidates for NAHT. Methods: The SAFIA trial is a prospective multicentre, international, double-blind, neoadjuvant phase-III trial using upfront 21-gene Oncotype DX Breast Recurrence Score assay (RS) <31) to select operable Luminal HER2-negative patients for induction hormonal therapy with Fulvestrant 500 mg +/– Goserelin (F/G) before randomizing responding patients to F/G + Palbociclib (Cyclin-Dependent Kinase 4/6 inhibitor / CDK 4/6) versus F/G + Placebo. The primary endpoint of this study was the complete pathologic response (pCR) rate. Results: A total of 354 patients were enrolled, leading to 277 patients treated with induction F/G. Of these, 253 responding patients were randomized to F/G fulvestrant with palbociclib or Placebo. Two hundred and thirty patients were evaluable for pathologic response. No statistically significant differences were identified in terms of pCR rates between F/G with palbociclib or placebo: 2% versus 7%, respectively. According to the radiologic responses post- induction F/G, the hormone sensitivity rate was 89.8%, while the clinical benefit of 8–9 months of neoadjuvant F/G was 96%. Safety in the MENA population was acceptable with a grade 3-4 neutropenia rate of 25% in the F/G plus palbociclib arm. The feasibility of performing the 21-gene breast recurrence score assay on core biopsy specimens was optimal in 96.4% of cases. Conclusions: The addition of palbociclib to neoadjuvant F/G did not show any additional benefit in terms of pathologic response, including pCR in neoadjuvant therapy of Luminal HER2-negative BC responding to induction F/G. The use of an upfront 21-gene assay appeared feasible on biopsy specimens, and the identification of tumors with RS<31 allowed to select endocrine sensitive patients, leading ultimately to a 96% clinical benefit with 8–9 months of F/G neoadjuvant therapy. Clinical trial information: NCT03447132. [Table: see text]