Initial real life experience with ribociclib in breast cancer: Outcome with focus on tolerance and cardiac toxicity.

Abstract

e13024 Background: CDK4/6 inhibitors, such as ribociclib, are a new class of medications that are used in combination with hormonal therapy to treat advanced or metastatic hormone receptor-positive, HER2-negative breast cancer. The primary objective of this study is to evaluate the tolerance and cardiac toxicity of ribociclib in all patients at our institution. Secondary objectives include progression free survival and response rates. Methods: Patients who received ribociclib between December 2018 and August 2020 were included. Rates of dose reduction and discontinuation of ribociclib were used as surrogate markers for intolerance and were compared to those reported in land-mark trials. QTc changes and cardiac adverse events (AEs) were also collected. Results: Thirty one patients were included. Ribociclib was administered in the first-, second-, third-, and fourth-line palliative hormonal therapy settings in 5 (16%), 14 (45%), 11 (35%) and 1 (3%) patients respectively and 8/31 (26%) received prior 1-4 palliative chemotherapy lines. Ribociclib was combined with letrozole in 21 (68%) and with fulvestrant in 10 (32%) patients. QTc interval was ≤ 470 msec in all patients prior to treatment and 11 (35%) patients had preexisting cardio vascular (non electro-conductive) co-morbidities. AEs related dose reduction was reported in 12 (39%) patients [bone marrow toxicity 6 (19%), QTc prolongation 4 (13%), abnormal liver function tests 1 (3%) and abdominal pain 1 (3%)]. Ribociclib was permanently discontinued due to AEs in 5 (16%) patients (2: prolonged QTc, 2: coronary events and 1: suspected allergic reaction). The median duration of follow up was 14 months. Objective response was evaluable in 28 patients [CR: 1 (3.6%), PR: 1 (3.6%), SD: 20 (71.4%) and PD: 6 (21.4%)]. The median progression free survival was 18 months (95% CI: 12.3-23.7). Conclusions: Although objective response rates were low in this mixed cohort of heavily pretreated patients, ribociclib combined with letrozole or fulvestrant has shown a robust progression free survival in real life practice. Treatment discontinuation rate is higher than that reported in clinical trials with stringent inclusion criteria. Ribociclib associated cardiac toxicity can be appropriately managed with careful monitoring.[Table: see text]