Metastasis de novo (MTDN) is associated with poor progression-free survival (PFS) in HR+/HER2- breast cancer treated with CDK4/6 inhibitors (ICDK4/6) in first line (1L)

Keywords

luminal breast cancer - CDK4/6 inhibitors - metastasis - metastasis de novo

Up to 20% of luminal (LU) BC patients (pts) will develop disease recurrence in the first ten years. The development of CDK4/6i has changed this paradigm by significantly improving objective response rates and PFS. Despite extensive translational research, no clear predictive biomarker of response to CDK4/6i has been identified.

Methods: data from LU BC (HR+/HER2-) pts treated in 1L with the three available iCDK4/6 (abemaciclib, AB, Ribociclib, RIB and Palbociclib, Pb) between December 2016 and June 2024 were retrospectively collected. We aimed to identify variables associated with PFS and overall survival (OS). Survival curves were calculated with the Kaplan-Meier method and compared with log-rank test. Median follow-up time was calculated with inverse Kaplan-Meier. All p values less than 0.05 were deemed significant.

Results: A total of 378 pts were included; 243 pts (64%) received iCDK4/6 in 1L. The median age was 57 years(y), the majority were females, 33% were pre-menopausal (pm). The majority (n = 122) had HER2=0. Ten pts had a BRCA mutation, and 96 pts (26%) had a PIK3CA somatic mutation. Most pts had a NST BC (n = 175). A total of 152 pts received adjuvant endocrinotherapy (HT), and 29 experienced disease progression during the first 24m. Eighty pts had MTDN, and 116 had visceral MT. Regarding the CDK4/6i used: 70 pts received AB; 83, RIB; 90, Pb. The most used HT associated was aromatase inhibitor (AI) (alone or with goserelin n = 166). Eighty-eight pts needed CDKis dose reduction (DR). Median PFS and OS were 32 months (m) and 67 m, respectively. PFS and OS progressively declined in subsequent lines. There was no difference in PFS (p = 0.16) or OS (p = 0.2) according to the different CDKis (AB, 36 and 52m; RIB, 29 and 51m; PB, 39 and 65m). Median OS has not been reached. 5-y OS rate was 65%. Pts with visceral MT (30 vs. 45m, p = 0.005) and MTDN (36 vs. 41m, p = 0.02) had worse PFS. Pm women had improved PFS (48 vs. 32m, p = 0.049). Pts treated with AI or TMX, with or without goserelin, + CDKi experienced better PFS versus those with fuvestrant + CDKi (44vs27, p = 0.005). DR and age (< or ≥ 70 y) had no impact on PFS. When comparing the different CDKi among them, no difference in efficacy was perceived in various scenarios. In the MTD subgroup, the use of AB and IA/TMX combinations were associated with better PFS.

Conclusion: MTDN and visceral MT are predictors of poor PFS in metastatic BC treated with CDKis in 1L. OS data will be presented at the Congress.

Corresponding author: Lucas de Amorim Gouvea (e-mail: [e-mail]).