105P - Subsequent treatments after progression on cyclin-dependent kinase 4/6 inhibitors: A multicentric real-world data study

Background

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) (Ribociclib, Palbociclib or Abemaciclib) plus endocrine therapy (ET) is the standard first-line treatment in hormone receptor-positive (HR+) human epidermal growth factor receptor two-negative (HER2-) metastatic breast cancer (MBC) patients (pts). There are no established treatment sequencing after disease progression with CDK4/6i.

Methods

We conducted a multicentric retrospective observational study with HR+/HER2- MBC pts who had disease progression with a CDK4/6i for MBC, between January 2016 - July 2023. Data were collected from medical records. The objectives were to compare Progression-Free Survival (PFS) and Overall Survival (OS) across different treatment options. Survival curves were estimated with Kaplan-Meier method and compared with pairwise log-rank test.

Results

We identified 222 pts (220 women, 2 men) with a mean age of 57.6±13.4 years at the time of metastatic disease diagnosis; 131 (59.5%) were postmenopausal. The majority had visceral disease (172 pts, 77.5%). CDK4/6i were used as 1st-line treatment in 182 pts (82.0%), as 2nd-line in 30 (13.5%) and as 3rd-line in 10 (4.5%). After progression with CDK4/6i, the next line of treatment included ET (68 pts, 30.8%), capecitabine (62 pts, 28.1%), paclitaxel (30 pts, 13.5%), rechallenge with a different CDK4/6i (14 pts, 7.7%), other chemotherapies (12 pts, 5.4%) and other treatments (17 pts, 7.6%). After progression with CDK4/6i, PFS was higher for capecitabine treated pts (16.5 months (mo), 95% CI [7.6, 32.1]) and the lowest with paclitaxel (5.6 mo, 95% CI [3.5, 8.2]). The OS was higher for pts who were rechallenged with a different CDK4/6i (24.6 mo, 95% CI [18.2, not reached - NR]), followed by ET (14.0 mo, 95% CI [12.2, NR]) and capecitabine (15.6 mo, 95% CI [10.4, 20.8]), and it was the lowest for paclitaxel (9.0 mo, 95% CI [4.8, 15.0], p<0.05).

Conclusions

In our cohort, PFS was longer for pts treated with capecitabine, while OS was the highest for pts treated with a different CDK4/6i or ET. The main limitation of this study is its retrospective nature and the non-random assignment. Our findings show a benefit in switching ET while maintaining CDK4/6i beyond progression or rechallenged with a different CDK4/6i.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.