Neoadjuvant endocrine therapy with or without palbociclib in low-risk patients: a phase III randomized double-blind SAFIA trial

K Alsaleh, H Al Zahwahry, A Bounedjar, M Oukkal, A Saadeddine, H Mahfouf, K Bouzid, A Bensalem, T Filali, H Abdel-Razeq, B Larbaoui, A Kandil, O Abulkhair, M Al Foheidi, M Ghosn, H Rasool, H Boussen, A Mezlini, A Haddaoui, J Ayari, M Al Ghamdi, H Errihani, N Abdel-Aziz, M Arafah, F Dabouz, M Bahadoor, S Kullab, J M Nabholtz, King Saud University, Riyadh, Kingdom of Saudi Arabia, and the International Cancer Research Group (ICRG), Sharjah, Unites Arab Emirates, K Alsaleh, H Al Zahwahry, A Bounedjar, M Oukkal, A Saadeddine, H Mahfouf, K Bouzid, A Bensalem, T Filali, H Abdel-Razeq, B Larbaoui, A Kandil, O Abulkhair, M Al Foheidi, M Ghosn, H Rasool, H Boussen, A Mezlini, A Haddaoui, J Ayari, M Al Ghamdi, H Errihani, N Abdel-Aziz, M Arafah, F Dabouz, M Bahadoor, S Kullab, J M Nabholtz, King Saud University, Riyadh, Kingdom of Saudi Arabia, and the International Cancer Research Group (ICRG), Sharjah, Unites Arab Emirates

Abstract

Background: 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.

Objective: 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.

Materials and methods: 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.

Results: 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.

Conclusion: Neoadjuvant hormonal therapy is feasible in a selected population with a low RS score of < 31 CLINICAL TRIAL: NCT03447132.

Keywords: 21-gene breast recurrence score assay; Breast cancer; Fulvestrant; Neoadjuvant hormone therapy; Palbociclib.

Conflict of interest statement

K. Alsaleh: Honoraria: Amgen, AstraZeneca, Novartis, Pfizer, Roche. Research grants: Pfizer and AstraZeneca. M. Oukkal: Advisory/Consultancy, Speaker Bureau/Expert testimony: Amgen; Roche, Novartis, Pfizer, Bayer. O. Abulkhair: Advisory Board: Pfizer, Roche, Lilly, Newbridge. Hikmat Abdel-Razeq: Honoraria: Hikma Pharmaceuticals, Sanofi, Roche. J.M. Nabholtz: Research grants: Pfizer, AstraZeneca, Genomic Health, MSD. Honoraria: Amgen, AstraZeneca, MSD, Novartis, Pfizer, Roche. H. Al Zahwahry, A. Bounedjar, A. Saadeddine, H. Mahfouf, K. Bouzid, A. Bensalem, T. Fillali, B. Larbaoui, A. Kandil, H. Boussen, M. Al Foheidi, Jihen Ayari, M. Al Ghamdi, H. Errihani, M. Ghosn, N. Abdel-Aziz, M. Arafah, F. Dabouz, M. Bahadoor, S. Kullab: None declared.

© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Figures

Fig. 1
Fig. 1
Patient selection flowchart

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