Efficacy analysis of CDK4/6 inhibitors (CDKi) + endocrine therapy (ET) treatment in hormone receptor-positive/HER2-negative (HR+/HER2-) advanced breast cancer (aBC): Biomarker analysis including chemoendocrine score (CES) by CDKi type in SOLTI-1801_CDK-PREDICT study.

Abstract

1065 Background: CDKi + ET improved progression-free survival (PFS) and ribociclib also overall survival (OS) in HR+/HER2- aBC first-line setting. Intrinsic subtypes (IS) are prognostic and predict benefit from CDKi + ET (Finn. SABCS 2017, Prat. JCO 2021, Tolosa. SABCS 2022). We previously reported a PAM50-based CES in HR+/HER2-negative early BC (Prat et al. CCR 2016). Here, we evaluated the association of CES with PFS following CDKi therapy in aBC. Methods: CDK-PREDICT prospectively evaluated 113 HR+/HER2- aBC patients (pts) treated in the first-line setting with CDKi + ET. RNA from FFPE metastatic tumors was analyzed at the nCounter (Nanostring Technologies) using a 72 custom gene panel including the PAM50 genes. CES was evaluated as a continuous variable, and categorically (CES-E[endocrine-sensitive], CES-I[intermediate] and CES-C[chemo-sensitive]) using the previously reported cut-offs. Multivariable analyses were used to test CES association with PFS. Results: The median follow-up for PFS was 18.5 m. PAM50 IS and CES distribution are shown. No statistically significant difference in mPFS by CDKi. CES (as a continuous variable or as group categories) was found significantly associated with mPFS. mPFS for CES-E pts was NR (95% CI: 26.0 - NR), 20.7m for CES-I (95% CI: 14.2 – 31.7m; HR= 1.98, p<0.05) and 11.7m for CES-C (CI 95%: 7.0 - 18.8; HR= 3.72, p<0.05). CES-C was associated with lower PFS compared to CES-I (aHR= 0.55, p=0.10) and CES-E (aHR= 0.29, p<0.05) independent of CDKi, ET, intrinsic subtype (Luminal versus not), endocrine sensitivity, onset metastatic and visceral disease. CES-C was significantly associated with higher expression of, MIA and lower expression of CCND1, CCNE1, FOXA1, MLPH and UBE2T compared with CES-E (p< 0.05). In CES-E pts mPFS for palbociclib was NR (IC95:22.9-NR) compare with 43.8 m for ribociclib (IC95: 12.0-NR); aHR=1.17 p=0.546), in CES-I pts mPFS for palbociclib was 18.9 m (IC95: 5.8-27.3) compare with 31.7 m for ribociclib (IC95: 12.2-NR); aHR=0.50 p=0.294), and in CES-C pts mPFS for palbociclib was 11.6 m (CI95: 2.7-15-7) compare with 10.0 m for ribociclib (CI95: 2.1-NR; aHR=0.48 p=0.102). Abemaciclib not reported due to low numbers (n=16). Conclusions: We confirmed independent prognostic value of CES in first-line setting, suggesting a not statistically significant benefit with ribociclib vs palbociclib in CES-I. [Table: see text]