Abstract PO4-17-04: CDK 4/6 inhibitor switching patterns in Swedish patients with metastatic breast cancer: 5-year update from the SIRI study

Abstract Background: CDK 4/6 inhibitors (CDK 4/6i) combined with endocrine therapy is a well-established treatment option in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). However, there is limited evidence on switching patterns within this class of drugs. The Swedish Ibrance Registries Insights (SIRI) study investigated CDK 4/6i switching patterns in real-world setting using a nationwide cohort of MBC patients. Methods: This was a retrospective study utilizing population-based Swedish Health Data Registers. The overall cohort included all breast cancer patients ≥ 18 years with ≥ 1 dispensation of palbociclib from January 2017 – June 2022. This subgroup analysis focused on patients with ≥ 1 dispensation of either ribociclib or abemaciclib in addition to palbociclib. Minimum follow-up was 3 months. CDK 4/6-I sequencing patterns in total and over time as well as time from the first CDK 4/6i to the subsequent, was investigated. No information on the reason for switching was available. Results: Out of a total 2314 patients with ≥ 1 dispensation of palbociclib, 256 patients (11%) had ≥ 1 dispensation of either ribociclib or abemaciclib, either prior to (60% of cases) or following (40 % of cases) palbociclib treatment. The share of patients with dispensation of 1 CDK 4/6i increased over the study period from 7% of the patients initiating treatment in 2017 to 15% in 2021. Of the total 2161 patients initiating CDK 4/6i treatment on palbociclib, about 5% were subsequently prescribed another CDK 4/6i. The median age at treatment initiation in patients with 1 dispensed CDK 4/6-i was similar to the overall study cohort (67.1 vs 68.4 years). Half of the patients identified with 1 CDK 4/6i were initiated on ribociclib and prescribed palbociclib subsequently. The second and third most common switches were palbociclib to abemaciclib (25%) and palbociclib to ribociclib (10%), respectively. Seven patients received all three CDK 4/6i. In terms of time to subsequent CDK 4/6i, 108 patients (42%) were prescribed a subsequent CDK 4/6i within three months of treatment initiation with ribociclib-palbociclib being the most common sequence in 74 patients whereas 17%, 8%, and 4% of switches happened 4-6, 7-9, and 10-12 months after treatment initiation, respectively. Seventy-two patients (28%) had a dispensation of a subsequent CDK 4/6i more than 12 months after initiation of the first CDK 4/6i, with palbociclib-abemaciclib being the most common switch. Conclusions: A relatively high proportion of Swedish patients treated with CDK4/6i is switched from one to another CDK 4/6i soon after treatment initiation, implying that this strategy might be applied mainly, but not solely, due to adverse events. The increased trend over time might be associated with the regulatory approval of new CDK4/6i over time. Future studies should focus on the potential impact of switching CDK 4/6i on treatment effectiveness and toxicity as these issues have yet not been clarified. Declaration of Interest: This study is sponsored by Pfizer. AV has reported receiving research funding from Roche. HL has reported receiving consultant/advisory fees from Lilly, Novartis, Daichii, Pfizer, MSD, Pierre Fabre, Astra-Zeneca and research funding from Roche. MJ and DN are employees of Pfizer. RL and ML are employees of Quantify Research and were paid consultants to Pfizer for this research. Table. Table. Citation Format: Henrik Lindman, Antonis Valachis, Rosa Lauppe, Mathias Lilja, Daniel Nyqvist, Maria Jakobsson. CDK 4/6 inhibitor switching patterns in Swedish patients with metastatic breast cancer: 5-year update from the SIRI study abstract. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-17-04.