Abstract P5-02-44: Efficacy analysis of CDK4/6 inhibitors in combination with endocrine therapy treatment in HR+/HER2- breast cancer according to PAM50 intrinsic subtype: primary results of SOLTI-1801_CDK-PREDICT study
Authors: Tolosa Pablo , Pascual Tomás , Hernando Cristina , Servitja Sonia , Fernández Adela , Brasó-Maristany Fara , Benitez Javier , Lema Laura , Ruano Yolanda , Parrilla Lucia , Roncero Ana María , Sánchez-Bayona Rodrigo , Alva Manuel , Villacampa Guillermo , Moreno-Villa María Rocío , Canes Jordi , Salvador Fernando , Prat Aleix , Ciruelos Eva 
Published: March 2023

Background: First-line treatment with cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) plus endocrine therapy (ET) has demonstrated efficacy in improving progression-free survival (PFS), overall response rate (ORR) and, more recently, ribociclib was also improve overall survival (OS) in hormone receptor-positive/HER2-negative (HR+/HER2-) advanced breast cancer (aBC). Unfortunately, most patients eventually progress and develop secondary or primary endocrine resistance. To date, no clinical or molecular markers have shown clinical utility in this setting. However, data from retrospective analysis suggest that intrinsic subtypes (IS) are prognostic and predict benefit from CDK4/6i+ET (Finn SABCS 2017, Prat. JCO 2021). Here, we have evaluated the impact of IS in PFS and ORR.

Methods: This study prospectively evaluated patients with HR+/HER2- aBC treated in the first-line setting with CDK4/6i + ET from February 2015 to January 2022 across 5 hospitals in Spain. Tumor biopsies had been performed within 90 days prior the patient started the CDK4/6i + ET. RNA from FFPE tumors was analyzed at the nCounter® (Nanostring Technologies) using a 72 custom gene panel including the PAM50 genes. The primary objective is to correlate the baseline PAM50 IS with PFS. The Kaplan-Meier method and multivariable cox model PFS analyses were performed adjusting for previous endocrine sensitivity, visceral disease, and metastatic onset disease. Secondary objectives were to estimate the ORR based on RECIST1.1 and its association with IS and the development of a prognostic algorithm that includes clinical and genomic data.

Results: From May 2020 to May 2022, 113 patients with PAM50 results who met all eligibility criteria, including sample quality, were included. IS distribution was 42.5% Luminal A, 46.9% luminal B, 7.1% HER2-enriched, 0.9% basal-like and 2.6% Normal-like (89.4% luminal vs 10.6% non-luminal). Baseline patient characteristics are shown in table 1. The median follow-up for PFS was 18.5 m (interquartile range 10.0 – 31.7m). Median PFS for Luminal vs no-luminal subtypes was 26.8 m (95% CI: 18.9 - 43.8 m) and 10.0 m (95% CI: 5.8 - 26.0 m) (adjusted hazard ratio [aHR]= 2.44 95% IC: 1.17 - 5.07). Median PFS by all IS was not reached (NR) for Luminal A (95% CI: 23.0 – NR); 19.5 m luminal B (95% CI: 15.7 - 27.3 m, aHR vs Luminal A= 1.98 95% IC: 1.09 - 3.62), 10.0 m HER2-E (95% CI: 4.4 - NR, aHR vs Luminal A= 2.75 95% IC: 1.05 - 7.18), 12.4 m Normal-like (95% CI: 5.8 - NR, aHR vs Luminal A= 19.35 95% IC: 2.32 - 160.89) and not estimable for basal-like (aHR vs Luminal A= 5.44 95% IC: 1.44 - 20.60). ORR was not significantly higher in Luminal B (55.1%) and HER2-E (57.1%) subtype versus luminal A (46.3%) (p=0.677). OS follow-up is still immature.

Conclusions: We confirmed the independent prognostic value of the PAM50 IS in first-line HR+/HER2- breast cancer treated with CDK4/6i+ET. Further gene expression analysis and development of a prognostic composite score is ongoing and will be presented at the conference.

This project has received a research grant from “Instituto de Salud Carlos III (ISCIII), Ministerio de Economía y Competitividad” (Spain) awarded within the National Research Program with reference PI 18/01408, co-funded with European Union ERDF funds.

Baseline patient characteristics

Citation Format: Pablo Tolosa, Tomás Pascual, Cristina Hernando, Sonia Servitja, Adela Fernández, Fara Brasó-Maristany, Javier Benitez, Laura Lema, Yolanda Ruano, Lucia Parrilla, Ana María Roncero, Rodrigo Sánchez-Bayona, Manuel Alva, Guillermo Villacampa, María Rocío Moreno-Villa, Jordi Canes, Fernando Salvador, Aleix Prat, Eva Ciruelos. Efficacy analysis of CDK4/6 inhibitors in combination with endocrine therapy treatment in HR+/HER2- breast cancer according to PAM50 intrinsic subtype: primary results of SOLTI-1801_CDK-PREDICT study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-02-44.