Real-world patterns of post-progression treatment and outcomes in patients with HR+/HER2- advanced breast cancer treated with CDK4/6 inhibitors

Patients and methods we retrospectively collected data of patients with HR+/HER2- advanced breast cancer (ABC) treated with endocrine therapy (ET) and a CDK4/6 inhibitor (CDK4/6i) aiming to describe the patterns of post-progression outcomes. Results Among 452 evaluable patients 325 were treated in the first-line setting. Median progression-free survival (mPFS) was 22.8 months overall and 29.7 months in patients treated in first-line setting. Factors associated with outcomes in multivariate analysis were the line of CDK4/6i therapy, de novo vs recurrent disease, visceral vs bone-only metastases, and primary endocrine resistance. A total of 300 patients progressed and 250 overall and 156 in the first-line cohort received a subsequent treatment. Visceral progression and CDK4/6i duration <12 months were associated with a higher likelihood of receiving anthracycline or taxanes (AT) as compared to ET +/- everolimus (EET). Post-progression PFS (PPFS) and post-progression OS (PPOS) were statistically significantly better with EET and capecitabine (C) over AT overall and in patients with visceral progression. Multivariate analysis confirmed a significant advantage for EET and C, while visceral progression retained a significant impact only on PPOS. After progression to the first post-CDK4/6i treatment C obtained a significant better PPOS as compared to other treatments. Conclusion We showed in a large real-world series that most patients with HR+/HER2- ABC failing CDK4/6i and ET unselected for the occurrence of molecular mutations retain endocrine sensitivity and may benefit of a subsequent ET +/- a targeted therapy delaying the need for chemotherapy regardless of site of progression and prior CDK4/6i therapy duration.