210P Real-world Outcomes in Patients (pts) with HR+/HER2– Metastatic Breast Cancer (mbc) and Germline/tumour BRCA Mutations (g/tbrca1/2m) Receiving 1St-Line (1L) CDK4/6i Plus Endocrine Therapy (ET)

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. 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. 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. 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.