Characteristics and outcomes of real-world (RW) patients (pts) with microsatellite instability-high (MSI-H) solid tumors treated with pembrolizumab monotherapy (P) after FDA approval.

Authors

null

Tamara Snow

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

Organizations

Flatiron Health, New York, NY, Foundation Medicine, Inc., Cambridge, MA

Research Funding

Other
Flatiron health Inc.

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.

OS and TTD in P-treated, pantumor MSI-H pts.

NMedian TTD,
mos [95% CI]
Median OS,
mos [95% CI]
N at risk at
12-mos
12-mos OS,
% [95% CI]
All Pts1295.5 [4.1-7.6]NR [14.6-NR]3862.7 [53.3-73.7]
CRC364.5 [2.8-9.2]NR [12.9-NR]971.8 [55.0-93.7]
Endometrial396.2 [3.0-11.0]NR [11.0-NR]1358.4 [42.9-79.5]
Other*546.1 [2.8-8.2]17.3 [9.9-NR]1660.3 [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 Details

Meeting

2020 ASCO Virtual Scientific Program

Session Type

Poster Session

Session Title

Developmental Therapeutics—Immunotherapy

Track

Developmental Therapeutics—Immunotherapy

Sub Track

Immune Checkpoint Inhibitors

Citation

J Clin Oncol 38: 2020 (suppl; abstr 3060)

DOI

10.1200/JCO.2020.38.15_suppl.3060

Abstract #

3060

Poster Bd #

124

Abstract Disclosures

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