449P - Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) plus endocrine therapy (ET) treatment in metastatic lobular breast cancer (mLBC): A retrospective cohort study

Background

CDK4/6i plus ET is the standard of care for HR-positive HER2-negative mBC. The trials that led to this combination approval included mainly patients (pts) with ductal breast cancer, while limited data are reported on LBC. However, LBC are characterised by a unique pattern of metastatic recurrence and different degrees of endocrine sensitivity. This study aims to analyse CDK4/6i combinations on mLBC pts survival outcomes.

Methods

In this retrospective cohort study, we analysed outcome data of pts with mLBC who received CDK4/6i plus ET as first-line treatment between January 2017 and December 2022. Kaplan-Meier method was used to estimate median progression-free survival (mPFS). Long-rank Mantel-Cox test was used to evaluate differences in outcomes between different subgroups and between drugs.

Results

The study included 30 pts with a median age at mBC diagnosis of 63.1 years. 8/30 (27%) pts had de-novo metastasis, and 22/30 (73%) had recurrent disease. As CDK4/6i, 13/30 (43%) pts received Palbociclib (P), 14/30 (47%) Ribociclib (R) and 3/30 (10%) Abemaciclib. As ET, 13/30 (43%) pts received Fulvestrant (F) and 17/30 (57%) Letrozole (L). The overall mPFS was 28.7 months (mos). There were no statistically significant differences in mPFS between pts treated with R vs P (29.5 vs 23.7 mos, HR 0.82 [0.31-2.21], p=0.7). Similarly, no significant differences were observed in pts with de-novo metastasis vs recurrent disease (29.5 vs 23.8 mos, HR 0.59 [0.20-1.74], p=0.3), and in pts with only-bone vs visceral metastasis (23.9 vs 28.7 mos, HR 0.92 [0.33-2.54], p=0.9). In line with the different endocrine sensitivity of the two groups, a much longer mPFS, even if not statistically different, was observed in pts treated with L vs F (35.1 vs 15.1 mos, HR 0.56 [0.20-1.57], p=0.2). A statistically significant difference was observed in mPFS of HER2-0 vs HER2-low LBC pts (29.5 vs 5.9 mos, HR 0.20 [0.05-0.79], p=0.02).

Conclusions

CDK4/6i plus ET is an effective treatment in pts with mLBC. However, there is a significant difference in clinical outcomes of pts with a HER2-0 vs HER2-low mLBC. This suggests that further research is needed to identify new biomarkers for a more tailored treatment choice in pts with LBC.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

C. von Arx: Financial Interests, Personal, Advisory Board, Receipt of consultation fees:Participation in a company sponsored speaker’s bureau: AstraZeneca; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: Pierre-Fabre, Gentili, Lilly, Novartis, Ipsen; Financial Interests, Personal, Other, Conference Fee and travel grant: Organon; Financial Interests, Personal, Other, Conference fee and travel grant: AAA. V. Di Lauro: Financial Interests, Personal and Institutional, Other, Honoraria: Novartis, Pfizer, Lilly, Roche, Gentili, Genetic, Exact Sciences, Pierre Fabre, Epionpharma.. R. Caputo: Financial Interests, Personal and Institutional, Other, Honoraria or speakers’ fee: AstraZeneca, Daiichi- Sankyo, Gilead, Veracyte, Pfizer, MSD, Seagen. . G. Buono: Financial Interests, Personal and Institutional, Other, Honoraria and speakers fee: Pierre Fabre, Novartis, GSK, Eli-Lilly, Pfizer, AstraZeneca, Roche, Daiichi Sankyo, Exact Science, Genetic. A. Verrazzo: Financial Interests, Personal and Institutional, Other, Travel Grant: Pierre Fabre. F. Nuzzo: Financial Interests, Personal and Institutional, Invited Speaker: Istituto Gentili and Pfizer.. M. De Laurentiis: Financial Interests, Personal and Institutional, Other, Honoraria and speakers fee: Pierre Fabre, Eli Lilly, Menarini, Gilead, Roche, AstraZeneca, Novartis, Pfizer, Seagen, Daiichi Sankyo, Genetic, GSK, Exact Sciences, Tomalab, Eisai, MSD, Sanofi Genzyme. All other authors have declared no conflicts of interest.