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Efficacy, safety, and predictive biomarkers of neoadjuvant nab-paclitaxel and pembrolizumab in hormone receptor-positive breast cancer: A randomized pilot trial.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: Efficacy, safety, and predictive biomarkers of neoadjuvant nab-paclitaxel and pembrolizumab in hormone receptor-positive breast cancer: A randomized pilot trial.
Συγγραφείς: Waks AG; Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA., Fu J; Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA., Chu X; Department of Data Sciences, Dana-Farber Cancer Institute, Boston, MA, USA., Binboga Kurt B; Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA., Li T; Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA., Kuntz TM; Harvard Chan Microbiome Analysis Core, Harvard TH Chan School of Public Health, Boston, MA, USA., Shen Y; Harvard Medical School, Boston, MA, USA.; Yale School of Medicine, New Haven, CT, USA., Yang D; Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA.; Department of Radiation Oncology, Dana-Farber Brigham Cancer Center, Boston, MA, USA., Meli K; Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA., Reardon B; Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Park J; Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA., Partridge A; Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA., Abravanel D; Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA., Jeselsohn R; Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA., Wrabel E; Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA., Alberti J; Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., DiLullo M; Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA., Chen S; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA., Mohammed-Abreu A; Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA., Sun X; Vanderbilt University Medical Center, Nashville, TN, USA., Balko JM; Vanderbilt University Medical Center, Nashville, TN, USA., Kleijn M; Agendia, Inc., Irvine, CA, USA., Audeh W; Agendia, Inc., Irvine, CA, USA., Morgan XC; Harvard Chan Microbiome Analysis Core, Harvard TH Chan School of Public Health, Boston, MA, USA., Krop IE; Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Yale Cancer Institute, New Haven, CT, USA., Tayob N; Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA., Van Allen EM; Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA., Mittendorf EA; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA.; Division of Breast Surgery, Department of Surgery, Brigham and Women's Hospital, Boston, MA, USA.; Division of Breast Surgery, Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA., Tolaney SM; Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. sara_tolaney@dfci.harvard.edu.; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA. sara_tolaney@dfci.harvard.edu.; Harvard Medical School, Boston, MA, USA. sara_tolaney@dfci.harvard.edu.
Πηγή: Nature communications [Nat Commun] 2025 Nov 28; Vol. 16 (1), pp. 10705. Date of Electronic Publication: 2025 Nov 28.
Τύπος έκδοσης: Journal Article; Randomized Controlled Trial
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
Imprint Name(s): Original Publication: [London] : Nature Pub. Group
Ιατρικοί όροι (MeSH): Paclitaxel*/administration & dosage , Paclitaxel*/therapeutic use , Paclitaxel*/adverse effects , Breast Neoplasms*/drug therapy , Breast Neoplasms*/metabolism , Breast Neoplasms*/genetics , Breast Neoplasms*/pathology , Albumins*/administration & dosage , Albumins*/therapeutic use , Albumins*/adverse effects , Antibodies, Monoclonal, Humanized*/administration & dosage , Antibodies, Monoclonal, Humanized*/therapeutic use , Antibodies, Monoclonal, Humanized*/adverse effects , Antineoplastic Combined Chemotherapy Protocols*/therapeutic use , Antineoplastic Combined Chemotherapy Protocols*/adverse effects, Neoadjuvant Therapy/methods ; B7-H1 Antigen/metabolism ; B7-H1 Antigen/genetics ; Biomarkers, Tumor/metabolism ; Biomarkers, Tumor/genetics ; Erb-b2 Receptor Tyrosine Kinases/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Humans ; Female ; Pilot Projects ; Middle Aged ; Adult ; Aged ; Treatment Outcome
Περίληψη: Patients with hormone receptor-positive (HR + )/HER2- breast cancer may benefit from neoadjuvant immune checkpoint inhibitor (ICI) plus chemotherapy. The effect of chemotherapy or ICI run-in before combination therapy in this population is unexplored. In this randomized pilot trial, patients with HR + /HER2- breast cancer received two weeks of neoadjuvant nab-paclitaxel or pembrolizumab, with baseline and post-run-in tumor biopsy, followed by combined nab-paclitaxel/pembrolizumab. The primary endpoint was PD-L1 expression change between biopsies. Tumor whole exome/RNA sequencing were performed. Of 29 patients, 72% were node-positive. Residual cancer burden (RCB) 0-1 rate was 28% (inclusive of patients receiving additional neoadjuvant adriamycin/cyclophosphamide). No significant change in PD-L1 expression occurred following nab-paclitaxel or pembrolizumab run-in, thus the primary endpoint was not met. Other secondary outcome measures included overall response rate of 80% to the neoadjuvant regimen, and 3-year event-free survival of 86% (95% CI 69-100%); there were no unexpected safety signals. In exploratory biomarker analyses, higher baseline PD-L1 expression and inflammatory gene signatures were associated with favorable response (RCB 0-1); higher expression of estrogen response genes, with unfavorable response (RCB 2-3). Clinical Trial Number: NCT02999477.
(© 2025. The Author(s).)
Competing Interests: Competing interests: A.G.W. reports consulting or advisory roles for AstraZeneca and AMBRX; speaker’s honoraria from AstraZeneca; and research support (to institution) from Genentech, Gilead, Macrogenics, and Merck. J.B. reports research support from Genentech/Roche and Incyte Corporation; has received advisory board payments from AstraZeneca, Eli Lilly, and Mallinckrodt; and is an inventor on patents regarding immunotherapy targets and biomarkers in cancer. M.K. and W.A. are employees of Agendia. B.R. reports having institutional patents filed on methods for clinical interpretation. E.A.M. reports compensated service on scientific advisory boards for AstraZeneca, BioNTech, and Merck; uncompensated service on steering committees for Bristol Myers Squibb and Roche/Genentech; speakers honoraria and travel support from Merck Sharp & Dohme; and institutional research support from Roche/Genentech (via SU2C grant) and Gilead. EAM also reports research funding from Susan Komen for the Cure for which she serves as a Scientific Advisor, and uncompensated participation as a member of the American Society of Clinical Oncology Board of Directors. S.M.T. reports consulting or advisory roles for Novartis, Pfizer/SeaGen, Merck, Eli Lilly, AstraZeneca, Genentech/Roche, Eisai, Bristol Myers Squibb/Systimmune, Daiichi Sankyo, Gilead, Blueprint Medicines, Reveal Genomics, Sumitovant Biopharma, Artios Pharma, Menarini/Stemline, Aadi Bio, Bayer, Jazz Pharmaceuticals, Natera, Tango Therapeutics, eFFECTOR, Hengrui USA, Cullinan Oncology, Circle Pharma, Arvinas, BioNTech, Launch Therapeutics, Zuellig Pharma, Johnson&Johnson/Ambrx, Bicycle Therapeutics, BeiGene Therapeutics, Mersana, Summit Therapeutics, Avenzo Therapeutics, Aktis Oncology, Celcuity, Boehringer Ingelheim, Samsung Bioepis, Olema Pharmaceuticals, Tempus, and Boundless Bio; research funding from Genentech/Roche, Merck, Exelixis, Pfizer, Lilly, Novartis, Bristol Myers Squibb, AstraZeneca, NanoString Technologies, Gilead, SeaGen, OncoPep, Daiichi Sankyo, Menarini/Stemline, Jazz Pharmaceuticals, and Olema Pharmaceuticals; and travel support from Lilly, Gilead, Jazz Pharmaceuticals, Pfizer, Arvinas, and Roche. The remaining authors declare no competing interests.
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Grant Information: P50 CA168504 United States CA NCI NIH HHS
Molecular Sequence: ClinicalTrials.gov NCT02999477
Substance Nomenclature: P88XT4IS4D (Paclitaxel)
0 (Albumins)
0 (Antibodies, Monoclonal, Humanized)
0 (B7-H1 Antigen)
0 (Biomarkers, Tumor)
EC 2.7.10.1 (Erb-b2 Receptor Tyrosine Kinases)
0 (Receptors, Estrogen)
0 (Receptors, Progesterone)
DPT0O3T46P (pembrolizumab)
0 (130-nm albumin-bound paclitaxel)
0 (CD274 protein, human)
EC 2.7.10.1 (ERBB2 protein, human)
Entry Date(s): Date Created: 20251128 Date Completed: 20251128 Latest Revision: 20260127
Update Code: 20260130
PubMed Central ID: PMC12663207
DOI: 10.1038/s41467-025-66667-y
PMID: 41315271
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:2041-1723
DOI:10.1038/s41467-025-66667-y