BRCA1/2 and other predisposition genes in high-risk hormone receptor+/human epidermal growth factor receptor 2- breast cancer treated with endocrine therapy with or without palbociclib: a secondary PENELOPE-B study analysis : original reports : biomarkers
Purpose - The PENELOPE-B trial (ClinicalTrials.gov identifier: NCT01864746) recruited patients with hormone receptor+/human epidermal growth factor receptor 2- early breast cancer without a pathological complete response after taxane-containing neoadjuvant chemotherapy and at a high risk of relapse....
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| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
April 10, 2025
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| In: |
JCO precision oncology
Year: 2025, Issue: 9, Pages: 1-9 |
| ISSN: | 2473-4284 |
| DOI: | 10.1200/PO-24-00742 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.1200/PO-24-00742 Verlag, kostenfrei, Volltext: http://ascopubs.org/doi/10.1200/PO-24-00742 
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| Author Notes: | Eric Hahnen, PhD1, Jan Hauke, PhD, Karen Gelmon, MD, Frederik Marmé, MD, Corinna Ernst, PhD, Miguel Martin, MD4, Michael Untch, MD, Hervé Bonnefoi, MD, Erik Knudsen, MD, Seock-Ah Im, MD, Angela DeMichele, MD, Laura Van’t Veer, MD, Sung-Bae Kim, MD, Harry Bear, MD, PhD, Nicole McCarthy, MD, Kerstin Rhiem, MD, Nicholas Turner, MD, Agnieszka Witkiewicz, MD, Federico Rojo, MD, Martin Filipits, MD, Lesley-Ann Martin, MD, Peter A. Fasching, MD, Christian Schem, MD, Kerstin Becker, PhD, José A. García-Sáenz, MD, Catherine M. Kelly, MD, Toralf Reimer, MD, Masakazu Toi, MD, Hope S. Rugo, MD, Carsten Denkert, MD, Michael Gnant, MD, Andreas Makris, MD, Yuan Liu, MD, Olga Valota, MSc, Bärbel Felder, PhD, Karsten Weber, PhD, Valentina Nekljudova, PhD, and Sibylle Loibl, MD |
| Summary: | Purpose - The PENELOPE-B trial (ClinicalTrials.gov identifier: NCT01864746) recruited patients with hormone receptor+/human epidermal growth factor receptor 2- early breast cancer without a pathological complete response after taxane-containing neoadjuvant chemotherapy and at a high risk of relapse. Patients were randomly assigned (1:1) to receive 13 cycles of palbociclib once daily or placebo on days 1-21 in a 28-day cycle in addition to endocrine therapy (ET). PENELOPE-B did not show improved invasive disease-free survival (iDFS) after adding palbociclib to ET. This retrospective analysis investigated the impact of germline pathogenic variant (PV) status of BRCA1/2 and non-BRCA1/2 cancer predisposition genes on the outcomes of PENELOPE-B trial patients. - Methods - In total, 445 patients were sampled following a case-cohort design and 442 were analyzed for germline PVs. Statistical analyses were performed for time-to-event end points (iDFS, distant disease-free survival [DDFS], and overall survival [OS]). - Results - Of the 442 patients, 42 carried PVs in any cancer predisposition gene; 15 carried BRCA1/2 PVs. Irrespective of the treatment arms, PV status was not a prognostic factor. Regarding the treatment arms in BRCA1/2 PV carriers, numerically better 3-year outcomes were observed in the palbociclib arm (iDFS, 95%; DDFS, 95%; OS, 100%) than in the placebo arm (iDFS, 72.8%; DDFS, 72.8%; OS, 87.5%; hazard ratios palbociclib v placebo 0.349 [iDFS] and 0.562 [DDFS], not calculated for OS, too few events). In patients without BRCA1/2 PVs, the differences in 3-year outcomes were negligible. PVs in non-BRCA1/2 cancer predisposition genes did not influence the efficacy of palbociclib, although gene-specific effects could not be excluded. - Conclusion - Patients with BRCA1/2 PVs had numerically better outcomes after palbociclib. However, the number of BRCA1/2 carriers was small. Larger randomized clinical trials should consider the PV status to further evaluate whether BRCA1/2 PV carriers benefit from cyclin-dependent kinase 4 and 6 inhibitor treatment. |
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| Item Description: | Gesehen am 10.06.2025 |
| Physical Description: | Online Resource |
| ISSN: | 2473-4284 |
| DOI: | 10.1200/PO-24-00742 |