A digital pathology AI model to predict immune-oncology biomarker status and pembrolizumab response in a real-world cohort of patients with colorectal and breast cancer.

e13617 Background: Deep learning (DL) algorithms have garnered significant attention for prediction of biomarker status in digitized tissue slides. Here, we trained and validated a digital pathology algorithm to predict microsatellite instability (MSI)/mismatch repair deficiency (MMRd) in colorectal cancer (CRC) and PD-L1 status in breast cancer (BC) using a large real-world patient cohort. Methods: H&E and immunohistochemistry (IHC) slides of CRC and BC from Caris Life Sciences (Phoenix, AZ) with known biomarker status were digitally scanned (CRC: N=27,494, 6.6% MSI-high by next-generation sequencing [NGS]; N=25,788, 6.4% MMRd by IHC; BC: N=16,069, 15.8% PD-L1+ by IHC). A transformer-based DL model (Wagner, Sophia J., et al., 2023) was trained to predict biomarker status, with 5-fold cross-validation. Accuracy, F1 score, area under the curve (AUC), and other metrics were calculated comparing the model to NGS/IHC “truth”. Risk stratification was performed on holdout datasets of pembrolizumab-treated CRC (N=422-454) and triple negative breast cancer (TNBC; N=513) pts. Post-treatment overall survival (OS) was calculated from start of pembrolizumab to last contact, per insurance claims data. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated by Cox-Proportional hazards and compared between model and “truth”. Results: When applied to holdout datasets for biomarker prediction, the validated model achieved AUC of 0.78-0.95. In CRC and BC, performance was better among primary specimens than metastatic. For MSI-H/MMRd risk stratification in pembrolizumab-treated CRC, HR for OS were comparable between model and “truth” for primary and metastatic cohorts. When applied to the TNBC holdout dataset, the model performed better than “truth” for PD-L1 risk stratification in pembrolizumab-treated pts. Conclusions: A digital pathology DL model predicts biomarker status with high accuracy and is non-inferior to NGS/IHC for risk stratification of pembrolizumab-treated CRC and TNBC pts. These results support further investigation of AI algorithms developed from large datasets as possible rapid screening tools for biomarker detection in molecular testing programs. [Table: see text]