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Purpose <p>Estrogen receptor-positive (ER+), HER2-negative (HER2-) metastatic breast cancer (MBC) shows variable outcomes after first-line CDK4/6 inhibitors (CDK4/6i) plus endocrine therapy (ET). The prognostic role of PAM50 intrinsic subtypes (IS) in this setting remains unestablished. We evaluated IS and biomarker profiles in the SOLTI-1801 CDK-PREDICT cohort, focusing on real-world second- and third-line progression-free survival (rwPFS-2L and rwPFS-3L).</p> Methods <p>This multicenter observational study reports a post hoc secondary analysis of ER+ /HER2- MBC patients previously treated with first-line CDK4/6i plus ET. Baseline metastatic biopsies were molecularly profiled (PAM50, <i>CCNE1</i>, <i>PDCD1</i>) using the nCounter platform. rwPFS-2L and rwPFS-3L were defined from initiation of second- or third-line therapy to progression or death. Kaplan–Meier and Cox models assessed associations with clinical, molecular, and treatment variables.</p> Results <p>Among evaluable patients (<i>n</i> = 125 for rwPFS-2L; <i>n</i> = 95 for rwPFS-3L), Luminal A/B subtypes represented most cases, while advanced lines showed more aggressive profiles. Median rwPFS-2L was 7.2&#xa0;months in luminal IS vs. 6.1 in non-luminal (HR 1.40; 95% CI 0.86–2.30); the Basal-like (BL) subtype correlated with significantly shorter rwPFS-2L (HR 3.82; 95% CI 1.07–13.63). In rwPFS-3L, similar trends were seen (6.4 vs. 3.3&#xa0;months; HR 1.74; 95% CI 0.98–3.08), with BL showing the poorest outcomes (HR 5.63; 95% CI 1.17–27.02). High <i>CCNE1</i> expression was linked to shorter rwPFS-2L (HR 1.22; 95% CI 1.02–1.47). Targeted agents were frequent in 2L (51%) and capecitabine in 3L (36%), while endocrine monotherapy yielded poorest rwPFS.</p> Conclusions <p>Outcomes after CDK4/6i progression differ by PAM50 IS, supporting its role in guiding post-progression treatment.</p>

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Real-world second- and third-line progression-free survival after progression on first-line CDK4/6 inhibitors in HR+/HER2- metastatic breast cancer by PAM50 intrinsic subtype: the SOLTI-1801 CDK-PREDICT study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月28日

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  • Pablo Tolosa,
  • Isabel García-Fructuoso,
  • Tomás Pascual,
  • Olga Martínez-Sáez,
  • Juan Miguel Cejalvo,
  • Sonia Servitja,
  • María Fernández Abad,
  • Javier David Benitez Fuentes,
  • Fara Brasó-Maristany,
  • Ester Sanfeliu,
  • Laura Lema,
  • Yolanda Ruano,
  • Lucía Parrilla,
  • Ana María Roncero,
  • María Ángeles Cobos,
  • Irene Díaz,
  • Karla Alicia Centelles López,
  • Rodrigo Sánchez-Bayona,
  • Manuel Alva,
  • Ainhoa Madariaga,
  • Guillermo Villacampa,
  • Fernando Salvador,
  • Agustín Sánchez-Belmonte,
  • Marcos Malumbres,
  • Aleix Prat,
  • Eva Ciruelos

摘要

Purpose

Estrogen receptor-positive (ER+), HER2-negative (HER2-) metastatic breast cancer (MBC) shows variable outcomes after first-line CDK4/6 inhibitors (CDK4/6i) plus endocrine therapy (ET). The prognostic role of PAM50 intrinsic subtypes (IS) in this setting remains unestablished. We evaluated IS and biomarker profiles in the SOLTI-1801 CDK-PREDICT cohort, focusing on real-world second- and third-line progression-free survival (rwPFS-2L and rwPFS-3L).

Methods

This multicenter observational study reports a post hoc secondary analysis of ER+ /HER2- MBC patients previously treated with first-line CDK4/6i plus ET. Baseline metastatic biopsies were molecularly profiled (PAM50, CCNE1, PDCD1) using the nCounter platform. rwPFS-2L and rwPFS-3L were defined from initiation of second- or third-line therapy to progression or death. Kaplan–Meier and Cox models assessed associations with clinical, molecular, and treatment variables.

Results

Among evaluable patients (n = 125 for rwPFS-2L; n = 95 for rwPFS-3L), Luminal A/B subtypes represented most cases, while advanced lines showed more aggressive profiles. Median rwPFS-2L was 7.2 months in luminal IS vs. 6.1 in non-luminal (HR 1.40; 95% CI 0.86–2.30); the Basal-like (BL) subtype correlated with significantly shorter rwPFS-2L (HR 3.82; 95% CI 1.07–13.63). In rwPFS-3L, similar trends were seen (6.4 vs. 3.3 months; HR 1.74; 95% CI 0.98–3.08), with BL showing the poorest outcomes (HR 5.63; 95% CI 1.17–27.02). High CCNE1 expression was linked to shorter rwPFS-2L (HR 1.22; 95% CI 1.02–1.47). Targeted agents were frequent in 2L (51%) and capecitabine in 3L (36%), while endocrine monotherapy yielded poorest rwPFS.

Conclusions

Outcomes after CDK4/6i progression differ by PAM50 IS, supporting its role in guiding post-progression treatment.