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<p>Poly(ADP-ribose) polymerase inhibitors (PARPi) are established as standard-of-care therapy for patients with hormone receptor-positive/HER2-negative advanced breast cancer (HR+/HER2− aBC) who harbor germline <i>BRCA1/2</i> likely pathogenic or pathogenic variants (LP/PV). However, the real-world efficacy of PARPi following tumor progression on first-line (1 L) cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) remains inadequately explored. In this cohort of 81 patients with HR+/HER2− aBC harboring germline <i>BRCA</i> LP/PV, 64 (79%) received 1 L treatment with CDK4/6i plus ET. Considering the subsequent therapy administered after tumor progression on 1 L CDK4/6i, patients treated with PARPi showed a significantly longer median real-world PFS (11.8 months) compared to those receiving ET, monochemotherapy, or polychemotherapy. This benefit was confirmed in a multivariable analysis, supporting PARPi as the preferred option in eligible patients. Our findings suggest that PARPi should be prioritized in the post-CDK4/6i treatment sequence for <i>BRCA</i> LP/PV carriers with HR+/HER2 aBC and highlight the critical role of germline <i>BRCA</i> testing.</p>

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Real-world effectiveness of PARP inhibitors after CDK4/6 inhibitor therapy in BRCA-mutated HR-positive/HER2-negative advanced breast cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月13日

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  • Emma Zattarin,
  • Antonio Marra,
  • Antonella Palazzo,
  • Gaia Griguolo,
  • Claudio Vernieri,
  • Julian Etessami,
  • Letizia Pontolillo,
  • Giusy Landa,
  • Arianna Daneri,
  • Matteo De Monte,
  • Riccardo Cuoghi Costantini,
  • Elena Tenedini,
  • Ornella Ponzoni,
  • Maria Grazia Razeti,
  • Caterina Sposetti,
  • Elena Barbieri,
  • Martina Manni,
  • Federica Caggia,
  • Laura Cortesi,
  • Giuseppe Curigliano,
  • Emilio Bria,
  • Massimo Dominici,
  • Valentina Guarneri,
  • Matteo Lambertini,
  • Angela Toss

摘要

Poly(ADP-ribose) polymerase inhibitors (PARPi) are established as standard-of-care therapy for patients with hormone receptor-positive/HER2-negative advanced breast cancer (HR+/HER2− aBC) who harbor germline BRCA1/2 likely pathogenic or pathogenic variants (LP/PV). However, the real-world efficacy of PARPi following tumor progression on first-line (1 L) cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) remains inadequately explored. In this cohort of 81 patients with HR+/HER2− aBC harboring germline BRCA LP/PV, 64 (79%) received 1 L treatment with CDK4/6i plus ET. Considering the subsequent therapy administered after tumor progression on 1 L CDK4/6i, patients treated with PARPi showed a significantly longer median real-world PFS (11.8 months) compared to those receiving ET, monochemotherapy, or polychemotherapy. This benefit was confirmed in a multivariable analysis, supporting PARPi as the preferred option in eligible patients. Our findings suggest that PARPi should be prioritized in the post-CDK4/6i treatment sequence for BRCA LP/PV carriers with HR+/HER2 aBC and highlight the critical role of germline BRCA testing.