Ki67 and progesterone receptor status predicts sensitivity to palbociclib: a real-world study

Abstract

Background: Palbociclib combined with endocrine therapy has been approved as a front-line treatment for hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2−) advanced breast cancer (ABC). A key challenge remains to uncover biomarkers to identify those patients who may benefit from palbociclib treatment.Methods: We retrospectively analyzed the values of Ki67 and progesterone receptor (PR) as detected by immunohistochemistry in 81 ABC patients with palbociclib and hormone therapy treatment, and evaluated the impact on progression-free survival (PFS).Results: In the total population, women with Ki67 ≥14% had marginally significantly shorter PFS than those with Ki67 <14% (P=0.062). Patients with Ki67 ≥30% had significantly shorter PFS than those with Ki67 <30% (P=0.048). Meanwhile, PR ≥20% was associated with longer PFS. Moreover, the change of Ki67 or PR from primary tissue to metastatic lesions was related to PFS. As for the hormone therapy subgroup, there were significant associations between Ki67 and PR levels and PFS in the aromatase inhibitors (AIs) subgroup. Patients with Ki67 ≥14% or Ki67 ≥30% had shorter PFS than those with Ki67 <14% or Ki67 <30%, respectively (P=0.024, P<0.001). Additionally, the change of Ki67 or PR from primary tissue to metastatic lesions was related to PFS. When both Ki67 and PR were considered, there were significant differences between the different cohorts. Compared with patients with Ki67 ≥14% and PR <20%, those with Ki67 <14% and PR ≥20% had significantly longer PFS. In addition, patients with Ki67 <30% and PR ≥20% had significantly longer PFS than those with Ki67 ≥30% and PR <20%. Furthermore, in the AI cohort, patients with Ki67 <14% and PR ≥20% had significantly longer PFS than those with Ki67 ≥14% and PR <20%. Women with Ki67 <30% and PR ≥20% had significantly longer PFS than those with Ki67 ≥30% and PR <20%. Conclusions:The present study indicates that both Ki67 and PR have great impacts on palbociclib and hormone therapy and may contribute to selecting more effective partners for palbociclib.

Which Clinicopathologic Parameters Suggest Primary Resistance to Palbociclib in Combination With Letrozole as the First-Line Treatment for Hormone Receptor-Positive, HER2-Negative Advanced Breast Cancer?

“…Previous research has suggested PgR and Ki-67 state to affect the efficacy of palbociclib ( 33 ). Our study also suggested that Ki-67 expression, but not PgR status, was related to PFS following a palbociclib-containing treatment.…”

Evaluating the Response of Palbociclib on Progression-Free Survival in Hormone Receptor-Positive Metastatic Breast Cancer

“…Rugo et al [5] found that the survival benefit of CDK4/6i was not associated with Ki67 expression in metastatic BC. In contrast, the recent study by Shao et al [4] showed that patients with Ki67 <14% and PR ≥20% had significantly longer PFS than those with Ki67 ≥14% and PR <20%. Hence, it is unclear from these previous studies whether Ki67 expression and PR expression can predict palbociclib efficacy.…”

“…Similarly, in the monarchE trial the authors found that high Ki67 levels (Ki67 ≥20%) showed benefit of abemaciclib and ET in the adjuvant setting for ER-positive, HER2- negative early-stage BC with high-risk features [17]. Although much effort has been exerted in the adjuvant setting, the prognostic benefit of Ki67 and PR expression to predict palbociclib efficacy in the metastatic setting is still not clear despite discussion in the literature [1, 4, 5]. Palleschi et al [1] showed that Ki67 can predict CDK4/6i + ET efficacy in metastatic BC but PR expression failed to show any benefit.…”

“…Although no single biomarker currently established is a gold standard, estrogen receptor (ER)/PR receptor status and Ki67 is the most widely used assessment technique because of its convenience and availability. PR expression and Ki67 index have been discussed in multiple studies as prognostic biomarkers for PFS [1,[4][5][6]. Thus, the use of surrogate biomarker to predict clinical outcome provides a greater opportunity in clinical decision-making.…”

Proliferation Marker Ki67 as a Stratification Index of Adjuvant Chemotherapy for Resectable Mucosal Melanoma

“…Ki67 is an important indicator of the cell proliferation rate for evaluating tumor malignancy and has been used to predict prognoses for various malignant tumor types (11). Recent studies using 30% as the cut-off Ki67 value for stratified analysis have likewise determined that a high Ki67 score (30%) is a potential prognostic marker and predictor of neoadjuvant or adjuvant chemotherapy efficacy in breast cancer and other malignant diseases (12)(13)(14)(15)(16). More specifically, a series of studies have indicated that the Ki67 level appears to be a strong and robust predictor of metastasis as well as an indicator of poor prognosis in melanoma (17)(18)(19)(20).…”