Abstract PO1-05-02: CDK4/6 inhibitors in advanced breast cancer (aBC). Preliminary results of the CDK4/6i choice and sequence of treatments in a series of 174 patients. GOIRC-04-2019 retro/prospective observational study
Authors: Moscetti Luca , Canino Fabio , Natalizio Salvatore , Sperduti Isabella , Barbieri Elena , Piacentini Federico , Omarini Claudia , Cortesi Laura , Barbolini Monica , Musolino Antonino , Frassoldati Antonio , Caggia Federica , Zoppoli Gabriele , Dominici Massimo , Toss Angela 
Published: May 2024

Abstract
Background: The sequence of treatments in aBC after a CDK4/6 inhibitor (i) is not defined yet. Fulvestrant (FUL), everolimus (E) combinations, and chemotherapy (CT) represents the main treatment options in Europe. Neither of these options has proven to be superior to the others. We conducted a retro/prospective, observational, non-randomized study, to evaluate the impact of subsequent treatments options after a 1st or 2nd line CDK4/6i in real-world clinical practice. Preliminary result in the retrospective series are presented. Methods: All patients (pts) who met the criteria to receive CDK4/6i plus aromatase inhibitors (AIs) or FUL, from market availability, were enrolled. 400 pts will be included; data from 200 pts will be collected retrospectively and 200 prospectively. Results: To date, 293 pts receiving CDK4/6i have been enrolled and the outcomes of 174 are available for a preliminary analysis. Characteristics of pts were as follow: M/F 1/173; ductal carcinoma 69%, lobular carcinoma 24%; de novo disease 28.6% In the relapse group, 46.5% pts were endocrine sensitive; 22% were endocrine resistant (7.9% and 14.1% secondary). 29.3% had bone-only disease, 46% visceral metastases only; 36% were Her2 score 0 and 64% score 1-2. 77% received CDK4/6i in 1st line, 23% in 2nd line.
In pts receiving 2nd line CDK4/6i, prior therapies (tx) were as follow: 34.5% taxanes, 43% other CT, 15% FUL, 8% E, 8% FUL. In the 1st line, 46% received palbociclib (P), 37% ribociclib (R) 21% abemacicib (A). In the second line P76%, R10%, A14%.
The subsequent treatments in the 49 pts who progressed after 1st line CDK4/6i was: 26% AIs/FUL +/-E, 74% CT. In the 28 pts who progressed after a 2nd line CDK4/6i tx: 20% FUL+/- E, 80% CT. The median lines of post CDK4/6i was 3 for both group (range 1-8 and 1-7).
Median progression free survival (mPFS) after 1st line CDK4/6i tx was 31 months (mo) (95% CI 21-39) and 22 mo (65% CI 14-21) after 2nd line CDK4/6i tx.
mPFS per CDK4/6i 1st line was as follow: P 23 mo, R 39.9 mo, A 23.2 mo. In 2nd line mPFS was: P 20 mo, R 14 mo, A 5 mo. No differences were observed between the three CDK4/6i but, if considering 1st and 2nd line together there was a difference in favor of R (p=0.009). Across five variables (ductal vs lobular; Her 2 score 0 vs 1/2, ki 67 &lt; 20 vs &gt;20, de novo vs recurrence, bone only vs other sites, type of CDK4/6i) no differences were observed in mPFS, except for bone only disease in 1st line setting (mPFS 46.7 vs 22,9 mo, p=0.007)
Median PFS in second line in the group who received 1st line CDK4/6i, was 5 mo in pts receiving CT and 7 mo in pts treated with FUL/E whereas, for pts receiving further tx after 2nd line CDK4/6i tx, was 7 mo in CT and 4 mo with FUL/E (p=ns).
Following the Sonia trial results, an analysis of PFS2 has been performed and in pts receiving CDK4/6i vs other therapies in 1st line (57 vs 91 pts), PFS2 was 24 mo vs 35 mo (p=0.014). Conclusion: The sequence of treatments after a CDK4/6i is far to be defined. In this preliminary analysis conducted in pts treated mainly in the years 2017-2019, CT represents the main choice after CDK4/6i failure. These data show the picture of the initial approach in the daily practice in an evidence-absent scenario. The increasing skill in the management of the CDK4/6i has changed in the last 5 years and we will proceed to complete the enrollment, in order to evaluate the difference in the choice of CDK4/6i and the sequence of tx in the prospective part of the study.
Citation Format: Luca Moscetti, Fabio Canino, Salvatore Natalizio, Isabella Sperduti, Elena Barbieri, Federico Piacentini, Claudia Omarini, Laura Cortesi, Monica Barbolini, Antonino Musolino, Antonio Frassoldati, Federica Caggia, Gabriele Zoppoli, Massimo Dominici, Angela Toss. CDK4/6 inhibitors in advanced breast cancer (aBC). Preliminary results of the CDK4/6i choice and sequence of treatments in a series of 174 patients. GOIRC-04-2019 retro/prospective observational 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 PO1-05-02.