Abstract 2551: Harness the power of real-world-data for oncology target and biomarker research: A case study by applying clinic-genomics data for 2,659 lung cancer patients and beyond
Authors: Wu Si , Zhao Weilong , Choi Christy , Cai Mona , Ansell Peter , Liede Alexander , Chen Rong , Zhao Xi , Samayoa Josue 
Published: March 2024

Abstract
Randomized controlled trials (RCTs) are the gold standard for evaluating drug safety and efficacy in controlled settings, but they have limited generalizability due to their focus on selective and homogeneous populations. Real-world-data (RWD), collected from larger and more varied patient populations, can address inherent limitations of RCTs and aid in clinical trial design and drug approval. However, with the challenges of RWD, unlocking its full potential for tumor target and biomarker identification and validation demands innovative analytical approaches. Here we present RWD analyses of ConcertAI® electronic health records (EHR) linked with Caris Lab data for 2,659 lung cancer patients. Comprehensive genomics analyses incorporate WES and RNA-seq data, coupled with rich clinical EHR data. By integrating clinical and genomics data, we showcase the potential of harnessing RWD as follows: (1) we investigated genomic alterations across five histology groups (adenocarcinoma, squamous, large cell, small cell lung cancer [SCLC], neuroendocrine [NE] lung cancer). Notably, TP53 and LRP1B mutations were prevalent across all groups. LRP1B mutations correlated with higher tumor mutation burden, indicative of a favorable response to immunotherapy. Biallelic TP53 and RB1 inactivation was predominant in SCLC and NE lung tumors. The five histological groups exhibit distinct expression profiles, reflecting tumor intrinsic characteristics. Most immune gene signature scores were significantly lower in SCLC and NE tumors, aligned with that they are cold tumors with immune resistance, except CD56-centered NK and neuroendocrine gene signatures; (2) we analyzed patient treatment patterns and persistence by line of therapy. Among the 206 NSCLC patients with clinically actionable EGFR mutations, 143 received targeted therapy during their treatment courses (69.4%). Time to treatment discontinuation (TTD) was used as a surrogate clinical outcome endpoint. TTD was significantly longer when TKI was the first line treatment compared to later lines (p = 0.01), while the trend is opposite for ICI where TTD is significantly shorter in the 1st line setting (p = 0.025); (3) we highlight the unique potential of leveraging H&E imaging modality in such RWD. In summary, we successfully identified unique molecular signatures among various lung cancer histological groups, pinpointed distinct subpopulations within lung adenocarcinoma and squamous tumors linked to their immune phenotypes, and investigated the different patient treatment patterns and outcomes, facilitating personalized medicine. In the broader context of our work, we have developed a framework for harnessing various data modalities (clinical, multi-omics, imaging) within AbbVie's oncology RWD realm, enhancing the discovery and validation of new oncology targets and biomarkers.
Citation Format: Si Wu, Weilong Zhao, Christy Choi, Mona Cai, Peter Ansell, Alexander Liede, Rong Chen, Xi Zhao, Josue Samayoa. Harness the power of real-world-data for oncology target and biomarker research: A case study by applying clinic-genomics data for 2,659 lung cancer patients and beyond [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2551.