{Reference Type}: Randomized Controlled Trial
{Title}: Neoadjuvant endocrine therapy with or without palbociclib in low-risk patients: a phase III randomized double-blind SAFIA trial.
{Author}: Alsaleh K;Al Zahwahry H;Bounedjar A;Oukkal M;Saadeddine A;Mahfouf H;Bouzid K;Bensalem A;Filali T;Abdel-Razeq H;Larbaoui B;Kandil A;Abulkhair O;Al Foheidi M;Ghosn M;Rasool H;Boussen H;Mezlini A;Haddaoui A;Ayari J;Al Ghamdi M;Errihani H;Abdel-Aziz N;Arafah M;Dabouz F;Bahadoor M;Kullab S;Nabholtz JM; ;
{Journal}: J Cancer Res Clin Oncol
{Volume}: 149
{Issue}: 9
{Year}: Aug 2023 21
{Factor}: 4.322
{DOI}: 10.1007/s00432-023-04588-3
{Abstract}: <B>BACKGROUND: </B>The most prevalent subtype of breast cancer (BC) is luminal hormonal-positive breast cancer. The neoadjuvant chemotherapy regimens have side effects, emphasizing the need to identify new startegies.<BR><B>OBJECTIVE: </B>Analyze the complete pathologic response (pCR) rate and overall response in a low-risk hormone-positive subset of patients receiving neoadjuvant hormone treatment (NAHT) with or without Palbociclib (a CDK4/CDK6 inhibitor) to boost NAHT effectiveness.<BR><B>METHODS: </B>Based on the upfront 21-gene Oncotype DX or low-risk Breast Recurrence Score assay (RS™), the SAFIA trial is designed as a prospective multicenter international, double-blind neoadjuvant phase-III trial that selects operable with luminal BC patients that are HER2-negative for the induction hormonal therapy with Fulvestrant 500 mg ± Goserelin (F/G) followed by randomization of responding patients to palbociclib versus placebo. The pCR rate served as the study's main outcome, while the secondary endpoint was a clinical benefit.<BR><B>RESULTS: </B>Of the 354 patients enrolled, 253 initially responded and were randomized to either F/G fulvestrant with palbociclib or placebo. Two hundred twenty-nine were eligible for the evaluation of the pathologic response. No statistically significant changes were observed in the pCR rates for the patients treated with the F/G therapy with placebo or palbociclib (7% versus 2%, respectively) per the Chevallier classification (Class1 + Class2) (p = 0.1464) and 3% versus 10% assessed per Sataloff Classification (TA, NA/NB) (p = 0.3108). Palbociclib did not increase the rate of complete pathological response.<BR><B>CONCLUSIONS: </B>Neoadjuvant hormonal therapy is feasible in a selected population with a low RS score of < 31 CLINICAL TRIAL: NCT03447132.