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

Humans Female Fulvestrant / therapeutic use Estradiol Neoadjuvant Therapy Prospective Studies Disease-Free Survival Receptor, ErbB-2 Breast Neoplasms / pathology Antineoplastic Combined Chemotherapy Protocols / adverse effects

21-gene breast recurrence score assay Breast cancer Fulvestrant Neoadjuvant hormone therapy Palbociclib

Journal

Journal of cancer research and clinical oncology

ISSN: 1432-1335

Titre abrégé: J Cancer Res Clin Oncol

Pays: Germany

ID NLM: 7902060

Informations de publication

Date de publication:
Aug 2023

Historique:

received: 01 12 2022

accepted: 11 01 2023

medline: 24 7 2023

pubmed: 22 1 2023

entrez: 21 1 2023

Statut: ppublish

Résumé

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

Sections du résumé

BACKGROUND 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 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 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 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 CONCLUSIONS

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

Identifiants

DOI: 10.1007/s00432-023-04588-3 PMID: 36680581 PMC: PMC9864499

pubmed: 36680581

doi: 10.1007/s00432-023-04588-3

pii: 10.1007/s00432-023-04588-3

pmc: PMC9864499

doi:

Substances chimiques

Fulvestrant 22X328QOC4

palbociclib G9ZF61LE7G

Estradiol 4TI98Z838E

Receptor, ErbB-2 EC 2.7.10.1

Banques de données

ClinicalTrials.gov

['NCT03447132']

Types de publication

Randomized Controlled Trial Multicenter Study Journal Article

Langues

eng

Sous-ensembles de citation

Pagination

6171-6179

Informations de copyright

Références

Ács B, Zámbó V, Vízkeleti L, Szász AM, Madaras L, Szentmártoni G et al (2017) Ki-67 as a controversial predictive and prognostic marker in breast cancer patients treated with neoadjuvant chemotherapy. Diagn Pathol 12(1):1–12

doi: 10.1186/s13000-017-0608-5

Allevi G, Strina C, Andreis D, Zanoni V, Bazzola L, Bonardi S et al (2013) Increased pathological complete response rate after a long-term neoadjuvant letrozole treatment in postmenopausal oestrogen and/or progesterone receptor-positive breast cancer. Br J Cancer 108(8):1587–1592

doi: 10.1038/bjc.2013.151 pubmed: 23579222 pmcid: 3668467

AlSaleh KA (2021) Clinical trials before, during, and after COVID-19 Pandemic. Am J Clin Oncol 44(2):90–91

doi: 10.1097/COC.0000000000000783 pubmed: 33475281

AlSaleh K, Al Zahwahry H, Bounedjar A, Oukkal M, Saadeddine A, Mahfouf H et al (2021) Response to induction neoadjuvant hormonal therapy using upfront 21-gene breast recurrence score assay—results from the SAFIA phase III trial. JCO Global Oncol 7:811–819

doi: 10.1200/GO.20.00575

Cristofanilli M, Turner NC, Bondarenko I, Ro J, Im SA, Masuda N et al (2016a) Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial. Lancet Oncol 17(4):425–439

doi: 10.1016/S1470-2045(15)00613-0 pubmed: 26947331

Curtis C, Shah SP, Chin S-F, Turashvili G, Rueda OM, Dunning MJ et al (2012) The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Nature 486(7403):346–352

doi: 10.1038/nature10983 pubmed: 22522925 pmcid: 3440846

Derouane F, van Marcke C, Berlière M, Gerday A, Fellah L, Leconte I et al (2022) Predictive biomarkers of response to neoadjuvant chemotherapy in breast cancer: current and future perspectives for precision medicine. Cancers 14(16):3876

doi: 10.3390/cancers14163876 pubmed: 36010869 pmcid: 9405974

Finn RS, Dering J, Conklin D, Kalous O, Cohen DJ, Desai AJ et al (2009) PD 0332991, a selective cyclin D kinase 4/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor-positive human breast cancer cell lines in vitro. Breast Cancer Res 11(5):R77

doi: 10.1186/bcr2419 pubmed: 19874578 pmcid: 2790859

Finn RS, Martin M, Rugo HS, Jones S, Im S-A, Gelmon K et al (2016) Palbociclib and letrozole in advanced breast cancer. N Engl J Med 375(20):1925–1936

doi: 10.1056/NEJMoa1607303 pubmed: 27959613

Fisher B, Jeong J-H, Bryant J, Anderson S, Dignam J, Fisher ER et al (2004a) Treatment of lymph-node-negative, oestrogen-receptor-positive breast cancer: long-term findings from national surgical adjuvant breast and bowel project randomised clinical trials. The Lancet 364(9437):858–868

doi: 10.1016/S0140-6736(04)16981-X

Fisher B, Jeong J-H, Bryant J, Anderson S, Dignam J, Fisher ER et al (2004b) Treatment of lymph-node-negative, oestrogen-receptor-positive breast cancer: long-term findings from national surgical adjuvant breast and bowel project randomised clinical trials. Lancet 364(9437):858–868

doi: 10.1016/S0140-6736(04)16981-X pubmed: 15351193

Goetz MP, Toi M, Campone M, Sohn J, Paluch-Shimon S, Huober J et al (2017) MONARCH 3: abemaciclib as initial therapy for advanced breast cancer. J Clin Oncol 35(32):3638–3646

doi: 10.1200/JCO.2017.75.6155 pubmed: 28968163

Haddad TC, Goetz MP (2015) Landscape of neoadjuvant therapy for breast cancer. Ann Surg Oncol 22(5):1408–1415

doi: 10.1245/s10434-015-4405-7 pubmed: 25727557 pmcid: 4484769

Hortobagyi GN, Stemmer SM, Burris HA, Yap Y-S, Sonke GS, Paluch-Shimon S et al (2016) Ribociclib as first-line therapy for HR-positive, advanced breast cancer. N Engl J Med 375(18):1738–1748

doi: 10.1056/NEJMoa1609709 pubmed: 27717303

Im S, Masuda N, Im Y, Inoue K, Kim S, Redfern A et al (2017) Efficacy and safety of palbociclib plus endocrine therapy in women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) in the Asia-Pacific region: Data from PALOMA-2 and-3. Ann Oncol 28:x27

doi: 10.1093/annonc/mdx654.003

Iwata H, Im S-A, Masuda N, Im Y-H, Inoue K, Rai Y et al (2017) PALOMA-3: phase III trial of fulvestrant with or without palbociclib in premenopausal and postmenopausal women with hormone receptor–positive, human epidermal growth factor receptor 2–negative metastatic breast cancer that progressed on prior endocrine therapy—safety and efficacy in Asian patients. J Global Oncol 3(4):289–303

doi: 10.1200/JGO.2016.008318

Iwata H, Masuda N, Yamamoto Y, Fujisawa T, Toyama T, Kashiwaba M et al (2019) Validation of the 21-gene test as a predictor of clinical response to neoadjuvant hormonal therapy for ER+, HER2-negative breast cancer: the TransNEOS study. Breast Cancer Res Treat 173(1):123–133

doi: 10.1007/s10549-018-4964-y pubmed: 30242578

Johnston S, Puhalla S, Wheatley D, Ring A, Barry P, Holcombe C et al (2019) Randomized Phase II study evaluating palbociclib in addition to letrozole as neoadjuvant therapy in estrogen receptor-positive early breast cancer: PALLET Trial. J Clin Oncol 37:178. 30523750

doi: 10.1200/JCO.18.01624 pubmed: 30523750

Koboldt D, Fulton R, McLellan M, Schmidt H, Kalicki-Veizer J, McMichael J et al (2012) Comprehensive molecular portraits of human breast tumours. Nature 490(7418):61–70

doi: 10.1038/nature11412

Loibl S, Turner NC, Ro J, Cristofanilli M, Iwata H, Im SA et al (2017) Palbociclib combined with fulvestrant in premenopausal women with advanced breast cancer and prior progression on endocrine therapy: PALOMA-3 results. Oncologist 22(9):1028–1038

doi: 10.1634/theoncologist.2017-0072 pubmed: 28652278 pmcid: 5599195

Marcus DM, Switchenko JM, Prabhu R, O’Regan R, Zelnak A, Fasola C et al (2013) Neoadjuvant hormonal therapy is associated with comparable outcomes to neoadjuvant chemotherapy in post-menopausal women with estrogen receptor-positive breast cancer. Front Oncol 3:317

doi: 10.3389/fonc.2013.00317 pubmed: 24409418 pmcid: 3873517

Paik S, Tang G, Shak S, Kim C, Baker J, Kim W et al (2006a) Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol 24(23):3726–3734

doi: 10.1200/JCO.2005.04.7985 pubmed: 16720680

Paik S, Tang G, Shak S, Kim C, Baker J, Kim W et al (2006b) Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor–positive breast cancer. J Clin Oncol 24(23):3726–3734

doi: 10.1200/JCO.2005.04.7985 pubmed: 16720680

Polley M-YC, Leung SC, McShane LM, Gao D, Hugh JC, Mastropasqua MG et al (2013) An international Ki67 reproducibility study. J Natl Cancer Inst 105(24):1897–906

doi: 10.1093/jnci/djt306 pubmed: 24203987 pmcid: 3888090

Reinert T, Barrios CH (2015) Optimal management of hormone receptor positive metastatic breast cancer in 2016. Ther Adv Med Oncol 7(6):304–320

doi: 10.1177/1758834015608993 pubmed: 26557899 pmcid: 4622303

Sahebjam S, Aloyz R, Pilavdzic D, Brisson M, Ferrario C, Bouganim N et al (2011) Ki 67 is a major, but not the sole determinant of oncotype Dx recurrence score. Br J Cancer 105(9):1342–1345

doi: 10.1038/bjc.2011.402 pubmed: 21970880 pmcid: 3241562

Slamon DJ, Neven P, Chia S, Fasching PA, De Laurentiis M, Im S-A et al (2018) Phase III randomized study of ribociclib and fulvestrant in hormone receptor–positive, human epidermal growth factor receptor 2–negative advanced breast cancer: MONALEESA-3. J Clin Oncol 36(24):2465–2472

doi: 10.1200/JCO.2018.78.9909 pubmed: 29860922

Sledge GW Jr, Toi M, Neven P, Sohn J, Inoue K, Pivot X et al (2017) MONARCH 2: abemaciclib in combination with fulvestrant in women with HR+/HER2− advanced breast cancer who had progressed while receiving endocrine therapy. J Clin Oncol 35(25):2875–2884

doi: 10.1200/JCO.2017.73.7585 pubmed: 28580882

Suman VJ, Ellis MJ, Ma CX (2015) The ALTERNATE trial: assessing a biomarker driven strategy for the treatment of post-menopausal women with ER+/Her2- invasive breast cancer. Chin Clin Oncol 4(3):34

pubmed: 26408301 pmcid: 4734643

WHO. Breast Cancer 2021 [updated 26th March, 2021]. Available from: https://www.who.int/news-room/fact-sheets/detail/breast-cancer . Accessed 2 Sep 2021

Turner NC, Slamon DJ, Ro J, Bondarenko I, Im S-A, Masuda N et al (2018a) Overall survival with palbociclib and fulvestrant in advanced breast cancer. N Engl J Med 379(20):1926–1936

doi: 10.1056/NEJMoa1810527 pubmed: 30345905

Yeo SK, Guan J-L (2017) Breast cancer: multiple subtypes within a tumor? Trends Cancer 3(11):753–760

doi: 10.1016/j.trecan.2017.09.001 pubmed: 29120751 pmcid: 5802368

Zhang T, Feng F, Yao Y, Qi L, Tian J, Zhou C et al (2019) Efficacy and acceptability of neoadjuvant endocrine therapy in patients with hormone receptor-positive breast cancer: a network meta-analysis. J Cell Physiol 234(8):12393–12403

doi: 10.1002/jcp.28068 pubmed: 30652307