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.
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.
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%)|
|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)|
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
Legal entity responsible for the study
Has not received any funding.
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.