Abstract P5-01-14: Real world evidence of continued CDK4/CDK6 inhibition and endocrine therapy beyond progression on a prior CDK4/6i in women with hormone receptor positive (HR+), Her2 negative advanced breast cancer (MBC)

Abstract Introduction: The use of endocrine therapy (ET) in combination with CDK4/6i is considered standard of care for patients with HR+, Her2 negative ABC. However, there remains an unmet need to determine the optimal sequencing after failure of CDK4/6i therapy. Endocrine monotherapy after progression to CDK4/6i is considered suboptimal treatment and access to other target therapies is limited in several countries. Two randomized trials (MANTAIN and postMONARCH) have supported the benefit of switching a different CDK4/6i and ET after progression to first line therapy with CDK4/6i. Evidence in a real-world setting of the efficacy of this approach is limited. Methods: In a retrospective multicenter study, we analyzed 30 Hispanic patients with HR+ Her2 negative advanced breast cancer treated with endocrine therapy and a CDK4/6i, who were switched to another ET with a CDK4/6i at progression. Primary outcome was to assess median progression free survival-1 (mPFS-1) for HR+ Her2- MBC to the first line with CDK4/6i and mPFS-2 after switching CDK4/6i and ET at progression. Secondary outcomes: To estimate mPFS-2 in relevant clinical subgroups as well as safety and tolerability. Results: From 2021-2024, 30 women with HR+Her2 negative MBC treated with a CDK4/6i in combination with ET were included. Median age at diagnosis was 56.5 years (SD 15.18), 67% were postmenopausal, 50% presented with metastatic de novo and 50% had recurrent disease. Regarding the site of metastatic disease, 53.3% had visceral and 40% only bone metastasis. 93.3% (n=28) received a CDK4/6i + ET as first line of therapy for MBC, 24 (80%) as a second line and 6 (20%) as a third line or beyond. Among those that received a CDK4/6i in the first line, 53.5% received palbociclib in combination with an AI (93%) as backbone ET. All premenopausal women (n=10) received GnRH agonist in combination with ET. At the second line, most patients received ribociclib (72.2%) combined with fulvestrant (87.5%). mPFS-1 to the first line with CDK4/6i was 19.7 (SD 14.1) months and 15.5 (32.0) months in the second line with the CDK4/6i continuation. In the subgroup analysis patients with only bone metastasis and a previous iCDK4/CDK6 treatment duration of more than 12 months showed a clinically meaningful benefit with a PFS of 26.8 (SD 47.7) months and 18.2 (SD 35.1) months respectively. Only 20% required dose reductions due to side effects and none had to interrupt CDK4/6i for toxicity. Conclusions: In this international real-world data cohort of Hispanic women with HR+Her2 negative ABC, the switch of CDK4/6i and endocrine therapy after first line therapy showed a clinically significant benefit in terms of PFS, specially in patients who received palbociclib in the first line setting and then switch to another CDK4/CDK6i and fulvestrant at progression, with a favorable toxicity profile. This strategy represents an appealing option in the current treatment landscape of HR+, Her2 negative MBC, specially in well selected patients and limited access to other target therapies. Citation Format: Roberto Sánchez-Reyes, Chavarri-Guerra Y, Villarreal-Garza C, Vázquez-Juárez D, Centelles K, Valdez-Sandoval P, Campos-Gómez S, Mantilla WA, Bravo-Garzón MA, Gomez H, Castro-Sánchez A, Talamantes-Gamez E. Real world evidence of continued CDK4/CDK6 inhibition and endocrine therapy beyond progression on a prior CDK4/6i in women with hormone receptor positive (HR+), Her2 negative advanced breast cancer (MBC) [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 P5-01-14.