Clinical Prognosticators in Patients Treated with CDK 4/6 Inhibitors for Hormone Receptors Positive Advanced Breast Cancer

Background: CDK4/6 inhibitors are the new standard of care in hormonal receptors positive (HR+) advanced breast cancer (ABC). Phase III trials demonstrated an improvement in survival outcomes in patients with combined endocrine approach compared to endocrine therapy (ET) alone. The aim of this retrospective study was to assess prognostic factors for clinical response to CDK4/6 inhibitors. Methods: All patients receiving CDK4/6 inhibitors from September 2016 to July 2019 were registered in a database. Data on tumor and patient’s characteristics as well as concomitant medications were collected. Survival data were analyzed by Kaplan Meier curves and log rank test. Treatment toxicities were graded according to CTCAE v5. A drug-drug interactions analysis among CDK 4/6 inhibitors and co-administered medications was performed too. Results: 121 patients were included in the study: 49% of patients treated in 1st -line, 25% in 2nd -line and 26% in 3rd –or further lines. 1st-line objective response rate (ORR) and clinical benefit rate (CBR) was 56% and 68%, compared to 40% and 50% in 2nd-line and 31% and 47% in heavily pre-treated patients, respectively. Median PFS according to line setting was: not reached in 1st-line, 17 months (95% CI 13-21) in 2nd-line and 7 months (95% CI 4-12) in 3rd or further lines. Negative prognostic factors in term of PFS were: previous chemotherapy for metastatic disease (p=0.0001), visceral metastatic sites (p=0.002) and endocrine sensitivity (p=0.001). No association among concomitant drugs administered and survival outcome was found. 94% of patients experienced neutropenia (G3-G4 60%) with 3% of febrile neutropenia. 71% of patients treated with Abemaciclib had diarrhea. Management of AE included 63% of treatment delay, 44% of 1st dose reduction and 15% of 2nd dose reduction, all due to neutropenia. No treatment discontinuation due to any toxicity was observed. Conclusion: Data on efficacy and safety profile of CDK 4/6 inhibitors administered outside the context of a clinical trial are consistent with those reported in Phase III trials. Previous chemotherapy for metastatic disease, visceral metastatic site as well as previous endocrine sensitivity negatively affect CDK 4/6 inhibitors efficacy. Concomitant medications did not affect survival outcome or safety profile.