Abstract 210P
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
| Events/N | Median (95% CI); months | ||
| Adjusted PFS | |||
| BRCAwt/unk | 1922/4288 | 22.0 (20.7–23.7) | |
| BRCAwt | 1105/2123 | 18.2 (16.9–20.1) | |
| BRCAunk | 817/2165 | 29.9 (26.9–33.6) | |
| BRCA1/2m | 99/141 | 14.3 (10.0–16.5) | |
| gBRCA1/2m | 55/78 | 12.4 (9.0–17.8) | |
| tBRCA1/2m | 44/63 | 15.1 (8.2–18.0) | |
| BRCA1m | 19/31 | 9.7 (7.2–18.4) | |
| BRCA2m | 75/102 | 14.3 (8.3–17.5) | |
| BRCA1/2m | 5/8 | NA | |
| PFS by ET partner | |||
| Fulvestrant | BRCAwt/unk | 638/1298 | 18.0 (16.2–21.0) |
| BRCA1/2m | 36/45 | 8.9 (5.3–17.8) | |
| Non-steroidal aromatase inhibitor | BRCAwt/unk | 1241/2857 | 24.5 (22.0–27.4) |
| BRCA1/2m | 63/92 | 14.6 (11.0–18.4) | |
| Other | BRCAwt/unk | 43/133 | 23.4 (16.1–NA) |
| BRCA1/2m | 0/4 | NA | |
| OS | |||
| BRCAwt/unk | 1726/4288 | 49.7 (48.3–53.1) | |
| BRCA1/2m | 69/141 | 40.7 (31.0–51.5) | |
| NA, non-analysable |
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.