Abstract Growing evidence suggests that enhancement of the tumor immune response contributes to the antitumor activity of CDK4/6 inhibitors (CDK4/6i), but the role of pretreatment tumor immune microenvironment is not clear. We retrospectively investigated in patients with HR+/HER2- advanced breast cancer receiving CDK4/6i and endocrine therapy whether pretreatment stromal tumor infiltrating lymphocytes (sTILs) were associated with outcome. A total of 100 patients were evaluable 53 treated with palbociclib, 44 with ribociclib and 3 with abemaciclib. Tumors were classified as sTILs positive (sTILs+) when sTILs were ≥ 10%. 58 tumors were sTILs negative (sTILs-) and 42 sTILs+. sTILs were not associated with any outcome overall and in the ribociclib cohort. Conversely, patients treated with palbociclib and sTILs+ tumors experienced a statistically significant improved overall survival (mOS Not Reached vs. 41.1 months, p = .038) and a reduced risk of visceral progression (24 vs. 8 patients p =.0048) as compared with patients with sTILs- tumors. Pretreatment sTILs levels were associated with outcome in patients treated with palbociclib. Given the lack of interaction between treatment and sTILs our findings warrant validation in larger, independent cohorts and if confirmed propose sTILs as a simple and reproducible biomarker to aid patient selection for palbociclib.
Torrisi et al. (2026) studied this question.