415P - Patterns of time-to-progression intervals across clinical and liquid biopsy (LB) features in hormone receptor-positive (HR+) HER2-negative (HER2-) metastatic breast cancer (MBC) patients (pts) treated with first-line endocrine therapy (ET)

Background

ET + a CDK 4/6 inhibitor (CDK4/6i) is the standard first-line therapy (1L) for HR+ HER2- MBC. Currently, imaging schedules are arbitrarily derived from clinical trials without margins of personalization. Aim of this study was to analyze the role of clinical and LB features in defining patterns of progression in HR+ HER2- MBC.

Methods

Pts were enrolled in the prospective multicenter CRO-2018-56 trial from January 2018 to January 2023. Serial CT scans and LB were performed. Prognostic factors were tested in terms of progression free survival (PFS) and overall survival (OS) through stepwise Cox regression. Progression distribution was estimated through smoothed hazard function.

Results

Of the 114 enrolled pts, 35% had de novo MBC, 15% invasive lobular carcinoma (ILC), 75% PgR+ disease. Bone was the most common metastatic site (75%). Most pts (96%) received ET + CDK4/6i (54% palbociclib, 37% ribociclib, and 9% abemaciclib). At baseline LB, 10% had ESR1-mutant (mut) MBC, 24% PIK3CA-mut. No ERBB2 mutations were detected. Median follow up was 34.8 months (mos). Histotype (ILC versus ductal [IDC], HR 5.66, P <0.0001) and liver involvement (HR 2.21, P = 0.027) were significantly associated with worse PFS. Significant prognostic factors for OS were histotype (HR 12.07, P <0.0001), PgR+ (HR 0.19, P = 0.003), de novo MBC (HR 6.89, P = 0.04) and PIK3CA-mut (HR 3.44, P = 0.03). Marked peak-hazard differences across timepoints were observed to histotypes (55 mos vs 2 mos for IDC and ILC, respectively), PgR status (55 mos for PgR+ vs 1.2 mos for PgR-) and liver involvement (55 mos for liver- vs 7.6 mos for liver+). Consistent distributions were observed for lung and bone involvement, de novo MBC, ESR1-mut and PIK3CA-mut.

Conclusions

Effective disease monitoring should balance the need for appropriate disease characterization while maintaining pts’ quality of life. Hazard distribution in HR+ HER2- MBC pts does not reduce overtime, but rather has different patterns across subgroups of interest. Further analyses are planned to define specific subgroups for personalized monitoring strategies.

Clinical trial identification

CRO-2018-56.

Editorial acknowledgement

Legal entity responsible for the study

IRCCS CRO.

Funding

Ricerca Finalizzata Ministero della Sanità RF-2016-02362544.

Disclosure

S. Spazzapan: Financial Interests, Personal, Advisory Board: MSD Italia, Seagen, AstraZeneca; Financial Interests, Personal, Invited Speaker: MSD, Novartis, Mundipharma, AstraZeneca, Eli Lilly; Financial Interests, Personal, Other, Congress registration: Pfizer; Financial Interests, Personal, Other, Tutoring: AstraZeneca; Financial Interests, Personal, Other, congress registration and travel expenses: Pfizer; Financial Interests, Personal, Other, Congress registration and travel expenses: Novartis; Financial Interests, Institutional, Local PI: AstraZeneca. F. Puglisi: Financial Interests, Institutional, Funding: AstraZeneca, Eisai; Financial Interests, Personal, Other: AstraZeneca, Roche, Amgen, Lilly, Novartis, Pfizer. All other authors have declared no conflicts of interest.