Flatiron Health, New York, NY
Tamara Snow , Akshay Swaminathan , Jeremy Snider , Alexa Betzig Schrock , Gerald Li , Brian Michael Alexander , Gaurav Singal , Emily Castellanos , Margaret Elizabeth McCusker
Background: The first tumor-agnostic, biomarker-based FDA approval in oncology was P in May 2017 for pts with MSI-H or mismatch repair (MMR) deficient tumors. 1 yr overall survival (OS) was >70% for colorectal cancer (CRC) and >60% for non-CRC in P-treated MSI-H clinical trial pts (Le 2019; Marabelle 2019). As tumor-agnostic therapies are a new paradigm, it is important to assess their use and effectiveness in routine clinical practice. We examined characteristics and outcomes of RW pts with MSI-H solid tumors who received P after May 2017. Methods: Pts with MSI-H solid tumors who received P after May 2017 were selected from the Flatiron Health-Foundation Medicine (FH-FMI) clinico-genomic database, a nationwide de-identified EHR-derived database linked to comprehensive genomic profiling (CGP) data. Pts with 2+ visits in the FH network from 01/2011-09/2019 with CGP prior to P use were included. Clinical characteristics were assessed at first P use. Time to treatment discontinuation (TTD) and OS from first P use were estimated with Kaplan-Meier analyses of all pts and the largest tumor types. Results: 33,395 pts had a solid tumor tested for MSI by CGP, of which 557 (1.7%) were MSI-H (median age 68 yrs; 34% male). 129 MSI-H pts across 33 tumor types received first P after May 2017. CRC (N=36) and Endometrial cancer (N=39) were most common. 52 pts (40%) had a concurrent MMR alteration (MLH1, MSH2, MSH6 or PMS2); median TMB was 32.2 mut/mb (IQR 20.9-47.5). Median number of therapies prior to P was 1; median time from CGP to first P use was 3 mos. Table shows OS and TTD. Conclusions: In this RW study, P use was observed across 33 MSI-H tumor types. Median OS exceeded 1 yr across all pts and in CRC, Endometrial, and Other cohorts. 1 yr OS rate was consistent with P trial outcomes. Further study should evaluate whether effectiveness differs across diseases, MSI testing method, or other genomic attributes to improve treatment selection.
N | Median TTD, mos [95% CI] | Median OS, mos [95% CI] | N at risk at 12-mos | 12-mos OS, % [95% CI] | |
---|---|---|---|---|---|
All Pts | 129 | 5.5 [4.1-7.6] | NR [14.6-NR] | 38 | 62.7 [53.3-73.7] |
CRC | 36 | 4.5 [2.8-9.2] | NR [12.9-NR] | 9 | 71.8 [55.0-93.7] |
Endometrial | 39 | 6.2 [3.0-11.0] | NR [11.0-NR] | 13 | 58.4 [42.9-79.5] |
Other* | 54 | 6.1 [2.8-8.2] | 17.3 [9.9-NR] | 16 | 60.3 [46.7-78.0] |
*Tumors included (largest to smallest N): Gastric, Occult/Unknown Primary, Prostate, Esophageal/Gastroesophageal Junction, Breast, Hepatobiliary, Small Intestine, Non-Small Cell Lung, Pancreatic, Ovarian
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Abstract Disclosures
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