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

## TL;DR

This study examines real-world treatment patterns and outcomes for patients with HR+/HER2− advanced breast cancer after CDK4/6 inhibitor therapy.

## Contribution

The study provides insights into post-progression treatment effectiveness in a real-world, unselected patient population.

## Key findings

- Endocrine therapy with or without targeted therapy showed better outcomes than chemotherapy after CDK4/6i failure.
- Visceral progression and short CDK4/6i duration were linked to higher chemotherapy use.
- Capecitabine improved survival after progression to first post-CDK4/6i treatment.

## Abstract

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.

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.

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.

Graphical Abstract