Palbociclib and letrozole for hormone receptor-positive HER2-negative breast cancer with residual disease after neoadjuvant chemotherapy
With the incorporation of cyclin-dependent kinase inhibitors in early breast cancer (BC), a better identification of biomarkers is needed. The PROMETEO II trial aimed to evaluate the antitumor activity of palbociclib plus letrozole and to identify response biomarkers in patients with operable HR+/HER2- BC and residual disease after neoadjuvant chemotherapy (NAC). The primary endpoint was the rate of complete cell cycle arrest (CCCA), centrally determined by Ki67 ≤ 2.7% at surgery. A comprehensive translational analysis was conducted. At surgery, the CCCA rate was 59.1%, with a 44.2% decrease in Ki67 from the end of NAC. Changes in intrinsic subtypes occurred in 48% of patients, with proliferation genes suppressed, and immune genes more upregulated in tumors with CCCA. Overall, 14% of tumors were classified as PD-L1<sup>+</sup> after palbociclib. Nine patients experienced grade 3 adverse events (AEs). Palbociclib showed an anti-proliferative effect, with increased immune infiltration in residual tumors with CCCA.Trial registration: Palbociclib Plus Letrozole in Hormone Receptor Positive Residual Disease After Neoadjuvant Chemotherapy (PROMETEO II) ClinicalTrial.gov number NCT04130152. Study registration; October 17, 2019.
Authors
- Antonia Perelló (ORCID: https://orcid.org/0000-0003-4137-8790)
- Eva Ciruelos
- Maria J. Merino (ORCID: https://orcid.org/0000-0003-2098-8426)
- Xavier González (ORCID: https://orcid.org/0000-0002-5797-7037)
- Sònia Pernas (ORCID: https://orcid.org/0000-0002-1485-5080)
- Guillermo Villacampa (ORCID: https://orcid.org/0000-0003-4868-6585)
- J.M. Ferrero-Cafiero (ORCID: https://orcid.org/0000-0001-8796-8812)
- Emilio Alba (ORCID: https://orcid.org/0000-0002-3364-2603)
- Tomás Pascual (ORCID: https://orcid.org/0000-0001-8431-3183)
- Lorea Villanueva (ORCID: https://orcid.org/0000-0003-1858-7076)
- Patricia Galván (ORCID: https://orcid.org/0000-0002-8153-0307)
- Esther Sanfeliu (ORCID: https://orcid.org/0000-0002-7974-3346)
- Begoña Jiménez
- Aleix Prat (ORCID: https://orcid.org/0000-0003-2377-540X)
- Samyukta Chillara (ORCID: https://orcid.org/0000-0002-6072-5455)
- J. Salvador
- Patricia Palacios
Institutions
- Breast Cancer Research Foundation (US)
- Instituto de Salud Carlos III (ES)
- Universitat Internacional de Catalunya (ES)
- Research Institute Hospital 12 de Octubre (ES)
- Instituto Oncológico Dr. Rosell (ES)
- Complejo Hospitalario Universitario de Santiago (ES)
- Open Evidence (ES)
- Institut Català d'Oncologia (ES)
- Centro de Investigación Biomédica en Red (ES)
- Hospital Clínic de Barcelona (ES)
- Hospital General de Catalunya (ES)
- Solti (ES)
- Hospital Universitario Son Espases (ES)
- Hospital Universitario Virgen del Rocío (ES)
- Hospital Clínico Universitario Virgen de la Victoria (ES)
- Centro de Investigación Biomédica en Red de Cáncer (ES)
- Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (ES)
- Hospital Universitario Infanta Sofía (ES)
- Instituto de Investigación Biomédica de Málaga (ES)
- Vall d'Hebron Institute of Oncology (ES)
- Universitat de Barcelona (ES)
Publication Details
- Journal
- npj Breast Cancer
- Published
- 2024-11-26
- DOI
- https://doi.org/10.1038/s41523-024-00710-x
- Citations
- 4
- Primary Topic
- Advanced Breast Cancer Therapies
- Type
- article
- Field-Weighted Citation Impact
- 1.68
Funders
- Eli Lilly and Company
- Pfizer
- AstraZeneca
- Gilead Sciences
- Les Laboratories Pierre Fabre
- Veracyte
- Seagen
- PharmaMar
- Instituto de Salud Carlos III
- Daiichi Sankyo Europe