Background

CDK4/6i + ET are recommended as 1L treatment in pts with HR+ HER2– mBC. However, treatment outcome in pts with BRCA1/2m (∼8% of pts) is not well understood. Here we report real-world (RW) outcomes to 1L CDK4/6i + ET by BRCA1/2m status from a large clinical-genomic database.

Methods

This was a retrospective cohort study of pts with HR+ HER2– mBC who received 1L CDK4/6i + ET captured in the Flatiron Health Data Repository from Jan 2011–June 2022. Primary endpoint was RW progression-free survival (PFS); RW overall survival (OS) was a secondary endpoint. Univariate (UV) and multivariate (MV; adjusted for ET and CDK4/6i) Cox proportional hazards models were used to compare outcomes in pts with deleterious g/tBRCA1/2m vs BRCAwt/unknown (unk) mutational status.

Results

The study included 4609 pts (145 BRCA1/2m and 4464 BRCAwt/unk); 4429 were evaluable for survival (141 and 4288, respectively). Compared to BRCAwt/unk, pts with BRCA1/2m had shorter PFS (14.3 [BRCA1/2m] vs 22.0 [BRCAwt/unk] months; UV hazard ratio [HR; 97.5% CI]: 1.95 [1.59–2.38], p≤0.0001; MV HR: 1.93 [1.70–2.36], p<0.0001) and OS (40.7 [BRCA1/2m] vs 49.7 [BRCAwt/unk] months; UV HR [95% CI]: 1.22 [0.95–1.23], p=0.122; MV HR: 1.21 [0.95–1.53], p=0.129). Further stratification of PFS mutation type and ET backbone is shown (Table). mPFS was consistently lower in pts with BRCA1/2m regardless of mutation type (g/t, BRCA1/BRCA2) and ET partner than in pts with BRCAwt/unk.

Conclusions

Pts with BRCA1/2m had significantly worse PFS outcomes with 1L CDK4/6i + ET than pts with BRCAwt/unk status. OS was also numerically lower in the BRCA1/2m cohort. Reductions in PFS were observed irrespective of mutation type (g/t or BRCA1/BRCA2) and ET partner. Optimised 1L treatment options are needed for pts with g/tBRCA1/2m HR+ HER2– mBC. Further research is needed to see if a similar trend is observed in early breast cancer.

Table: 210P

Editorial acknowledgement

AstraZeneca-funded medical writing support was provided by Suzanne Patel, Ph.D., from BOLDSCIENCE Inc.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

E. Nizialek, I. Gibson: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. S. Khosla: Financial Interests, Personal and Institutional, Leadership Role: AstraZeneca. E. Sofianopoulou, N. Lukashchuk, J.S. Brown: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. M. Robson: Financial Interests, Personal, Other, Review guideline pathways: Change Healthcare; Financial Interests, Personal, Invited Speaker, Speaker at CME events (NOT speaker's bureau): Physician's Education Resource, Research to Practice, Intellisphere, MJH Holdings; Financial Interests, Personal, Advisory Board, Speaker at CME events (NOT speaker's bureau): MyMedEd; Financial Interests, Institutional, Invited Speaker, Funding for research study (ICEBERG, dating to 2007): AstraZeneca; Financial Interests, Personal, Invited Speaker, Steering Committee Member for CAPITELLO-290, uncompensated: AstraZeneca; Financial Interests, Institutional, Other, Co-PI for Merck IIT of neoadjuvant olaparib/pembrolizumab in BRCA carriers, no personal compensation: Merck; Financial Interests, Personal, Invited Speaker, Steering Committee member for KEYLNK-009, no compensation: Merck; Financial Interests, Institutional, Invited Speaker, Local PI of KEYLNK009: Merck; Financial Interests, Institutional, Other, Local co-PI of clinical trial of ZEN03694 and talazoparib in TNBC, no personal compensation: Pfizer; Non-Financial Interests, Advisory Role: Zenith Pharmaceuticals, Epic Biosciences, Daiichi Sankyo, Tempus Labs; Non-Financial Interests, Personal, Other, Editorial services for writing of reports for ABRAZO clinical trial: Pfizer; Non-Financial Interests, Personal, Other, Editorial services for medical writing of reports resulting from OlympiAD trial: AstraZeneca; Non-Financial Interests, Member: ASCO. P. Razavi: Financial Interests, Personal, Advisory Board: Novartis, AstraZeneca, Epic Science, Inivata, SAGA Diagnostics, Prelude Theraputics, Paige.ai; Financial Interests, Personal, Ownership Interest: Odyssey Biosciences; Financial Interests, Institutional, Funding: Grail Inc., Novartis; Financial Interests, Institutional, Research Grant: AstraZeneca, Tempus, Guardant, Biotherenostics, Epic Sciences, Inviate; Non-Financial Interests, Advisory Role: Tempus. All other authors have declared no conflicts of interest.