Survival Outcomes, Multidimensional Prediction and Subsequent Therapy in Patients with Hormone Receptor-positive Advanced Breast Cancer Receiving Palbociclib: a Real-world Analysis

Background: To date, the overall survival (OS) of hormone receptor-positive advanced breast cancer (ABC) treated with palbociclib has not been reported in Chinese patients. It still remains unclear what kind of patients may benefit in OS from palbociclib treatment and what the optimal sequential antineoplastic regimen is for those progressing on palbociclib. Therefore, we aimed to investigate the OS outcome of ABC patients receiving palbociclib, establish a predictive model to identify the potential candidates who may benefit from palbociclib and explore the ideal subsequent treatment strategy after palbociclib.

Methods: This is a single-center ambispective real-world analysis of palbociclib in hormone receptor-positive ABC from April 2018 to August 2021. The patients were followed up via telephone or clinic visit. Progression-free survival (PFS), OS, overall response rate and time to second disease progression (PFS2) were evaluated as prognosis outcomes. Cyclin-dependent kinases 4/6 inhibitor (CDKI) score was established to predict OS benefit on the basis of tumor burden, line of palbociclib treatment and tumor marker.

Results: Fifty patients were included with the median PFS of 9.57 months and the median OS of 33.60 months. Age <65 years [hazard ratio (HR) 0.33, P=0.008], lung or liver involvement (HR 3.01, P=0.005) and > first line palbociclib therapy (HR 2.13, P=0.03) were independent unfavorable prognosticators for PFS. Positive estrogen receptor (ER) (HR 0.22, P=0.004), metastatic sites <3 (HR 3.59, P=0.02), absence of lung or liver involvement (HR 3.77, P=0.058) and PFS ≥12 months during palbociclib regimen (HR 0.14, P<0.001) could predict longer OS. CDKI score discriminated OS significantly (HR 4.41, P=0.009) and the CDKI score-based models were multidimensionally verified with satisfying performance, among which the area under the curve of receiver operating characteristic reached 0.835 and the C-index was 0.72. Moreover, chemo-free regimens saw improvement in time to second disease progression (HR 0.32, P=0.006) and OS (HR 0.32, P=0.049) for patients progressing on palbociclib compared with chemotherapy-based regimens.

Conclusions: CDKI score is a practical and comprehensive tool in predicting OS benefit for ABC patients treated with palbociclib, which deserves further validation. Patients who progressed on palbociclib seem to keep benefiting from chemo-free antineoplastic treatments. These findings may help identify the candidates for CDK4/6 inhibitor and optimize the strategies for hormone receptor-positive ABC.