Abstract P5-01-12: Subsequent Treatments After Progression On Cyclin-Dependent Kinase 4/6 Inhibitors - A Multicentric Portuguese Real-world Data Study

Abstract 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 guidelines on subsequent treatment after disease progression with CDK4/6i, especially in later lines. Methods: We conducted a multicentric retrospective observational study including HR+/HER2- MBC pts who experienced disease progression with a CDK4/6i for metastatic disease, between January 2016 and July 2023. Data were collected from medical records. The primary 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 the 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 a first-line treatment in 182 pts (82.0%), as second-line in 30 (13.5%) and as third-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]). However, 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 those on 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 those treated with 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 those treated with a different CDK4/6i or ET. The main limitation of this study is its retrospective nature and the non-random assignment of treatments. Thus, our findings support emerging data suggesting a benefit in switching ET while maintaining CDK4/6i after progression. Citation Format: Ana Rita Rego Freitas, Inês F. Eiriz, Marta Vaz Batista, Andreia Chaves, Catarina Santos, Tiago Barroso, Sara Cabral, Pedro Meireles, Ana R. Fortuna, Vanessa Patel, João P. Araújo, Tânia Duarte, Tiago P. Cabral, Sandra C. Silva, Joana Gonçalves, Isabel Fernandes, Inês Dunões, Cláudia Viana, Sofia Prada, Sofia Azambuja Braga. Subsequent Treatments After Progression On Cyclin-Dependent Kinase 4/6 Inhibitors - A Multicentric Portuguese Real-world Data Study [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P5-01-12.