Abstract 237P
Background
ICI showed benefit in PD-L1+ triple-negative BC and solid tumors with hTMB (≥ 10 mut/Mb). There is limited data on ICI treated HR+HER2- BC. Prior work showed that 7% of HR+HER2- BC has hTMB, with an enrichment in lobular carcinoma (15%) and most harboring APOBEC signature (70%). The purpose of this study was to describe real-world time-totreatment-discontinuation (rwTTD) for hTMB HR+HER2- mBC patients (pts) treated with ICI.
Methods
Pts with HR+HER2- mBC from the nationwide (US-based) de-identified Flatiron Health (FH)-Foundation Medicine (FMI) Clinico-Genomic database (CGDB) with genomic profiling by FMI between 01/2011 – 09/2020 and ICI initiation ≥ 6 months (mo) prior to cutoff date were eligible. rwTTD was measured as the difference between the last and first drug episode within a given line of treatment (LOT). LOTs were derived based on FH algorithms. The de-identified EHR data came from ∼280 US cancer clinics (∼800 sites of care). Eligible pts from Mayo Clinic and Duke University were HR+HER2- mBC pts with hTMB tested via FMI between 09/2013 – 07/2020. Clinical data were manually extracted. Similar rwTTD was measured within a given oncologist-defined LOT.
Results
Of 103 eligible pts in CGDB, 20/103 had hTMB. 5/20 pts had ≥ 6 mo on ICI; their TMB was between 16.3-255.8 mut/Mb. 1/5 received ICI with chemotherapy. At Mayo and Duke, there were 37 eligible pts, 8/37 started ICI ≥ 6 mo prior to cutoff date. 4/8 pts had ≥ 6 mo on therapy, their TMB was between 15-74 mut/Mb, and 3/4 had ICI with chemotherapy. Table: 237P
HR+ HER2- hTMB mBC pts who received ICI in Mayo/Duke and CGDB cohorts
| Mayo/Duke (n=8) | CGDB (n=20) | |
| APOBEC | 6 (75%) | 13 (65%) |
| Median TMB (IQR) | 32.5 (23.2, 47.5) | 20.9 (13.8, 33.8) |
| ICI Monotherapy | 2 (25%) | 14 (70%) |
| ICI Line | ||
| 1-2 | 3 (37.5%) | 1 (5.0%) |
| 3+ | 5 (62.5%) | 19 (95%) |
| ICI > 6 mo | 4 (50.0%) | 5 (25.0%) |
| Median TTD (mo, 95%CI) | 5.8 (2-NA) | 2.8 (1.4-NA) |
Conclusions
All cohorts included a subset of pts with ≥ 6 mo of ICI treatment. These pts tended to have hTMB and several received ICI with chemotherapy. Further studies are needed to identify a subset of HR+HER2- pts who are more likely to have durable response to ICI.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
S. Chumsri: Non-Financial Interests, Institutional, Research Grant: Merck; Non-Financial Interests, Institutional, Research Grant: Pfizer. E. Sokol, N.A. Danziger, K. Raskina, K. Mcgregor: Financial Interests, Personal, Full or part-time Employment: Foundation Medicine. A.B. Schrock, J. Venstrom, T. Snow, E. Castellanos, E. Ochuonyo: J. Snider Financial Interests, Personal, Full or part-time Employment: Flatiron. All other authors have declared no conflicts of interest.