Outcomes with CDK4/6 inhibitor in metastatic hormone receptor–positive breast cancer: Insights from a tertiary care centre in India.

e13086 Background: Cyclin dependant kinase 4/6 inhibitors (CDKi), along with endocrine therapy (ET), is the first line management of metastatic hormone receptor-positive HR+/Her2 neu negative cancer. This study provides real world outcomes from a resource constrained setting with respect to treatment patterns and prognostic factors of patients with metastatic HR+ breast cancer treated with cyclin dependant kinase (CDKi). Methods: We conducted a retrospective cohort study of patients diagnosed with HR+ metastatic breast cancer and treated with CDK4/6 inhibitors at All India Institute of Medical Sciences, India. The primary end point of the study was progression-free survival (PFS) and the secondary endpoint was overall survival (OS), response rates and adverse events. Ovarian function suppression was administered as per institution protocol. Results: A total of 240 patients were included, with a median age of 48 (26-54) years. Out of 240 patients,119(50%) were postmenopausal. CDKi was used in 59.6% (n = 143) of the cases with de novo metastatic disease and in 27.9% (n = 67) with relapsed disease. The sites of metastases were skeletal (70.8%), liver (22.9%), central nervous system (5%), non-regional nodal (48.8%) and pulmonary (47.5%). Visceral crisis was present in 8.8% (n = 21) patients. In the whole cohort 199 (82.9%) patients received palbociclib, 35 (14.6%) received ribociclib and 6 (2.5%) received abemaciclib. The objective response rate (ORR) was 44.9% and the clinical benefit rate (CBR) was 86.7%. Complete response (CR) was seen in 13.8%, partial response was seen in 30.4% and stable disease in 41.7%. Amongst the patients who presented with visceral crisis, the response rates were similar to patients without visceral crisis. The median follow-up duration was 39.06 (0.3-127.83) months. The median PFS was 17.23 months(3.7-37.09 months) and the median OS was 56.8(6-58.37). There was no difference in OS with use of CDKi in first line versus second line (p = 0.275). Grade 3/4 toxicity was present in 59 (24.6%) patients and level 1 dose reduction was performed in 13.3% patients. The most common grade 3/4 toxicity was neutropenia (18.75%), thrombocytopenia (3.33%) and anemia (2.5%). Additionally, 3 patients had hepatic toxicity and 2 patients had QTc prolongation on ribociclib. Ki-67 ≥20% emerged as the only significant independent predictor of PFS (HR: 2.78, p = 0.03). The only significant factor having an impact on OS was number of metastatic sites more than 3 (HR: 6.98, p = 0.008). Conclusions: This represents the largest data of CDKi from the Indian subcontinent. The OS and PFS reported are similar to real-world studies even though the complete remission rates and adverse events were lower than western data which could be attributed to difference in tumor biology. There is no difference in survival with use of CDKi in first line versus subsequent lines.