Improved outcomes from reflex comprehensive genomic profiling-guided precision therapeutic selection across a major US healthcare system.
Authors: Piening Brian , Bapat Bela , Weerasinghe Roshanthi K. , Meng Ryan , Dowdell Alexa K. , Chang Shu-Ching , Vita Ann , Wong Cliff , Tinn Robert , Harold Lauren , Schroeder Brock , Poon Hoifung , Febbo Phillip G. , Bifulco Carlo Bruno 
Published: June 2023

6622

Background: An ever-increasing number of biomarker-guided therapies, some with pan-cancer indications have expanded the oncologist’s toolbox for fighting advanced cancer. Despite this, not all advanced cancer patients receive tumor genomic testing, or are tested for a limited number of targets. Still others are tested too late in their care journey to benefit from precision therapy. To assess the impact of removing testing barriers, we developed a reflex testing protocol where comprehensive genomic profiling (CGP) was routinely ordered by pathologists at time of diagnosis for advanced cancer patients. Methods: Reflex CGP testing was primarily initiated by the pathologist at the time of advanced cancer diagnosis. Testing was performed between 2019 and 2021 via CGP using the ProvSeq 523 lab-developed test, and testing was performed at no cost to the patient. Post-CGP, stage 4 patients were followed for ≥ 12 months. We assessed time to therapy, therapy selection, and overall survival (OS). Therapies were stratified by presence of biomarkers associated with approved targeted therapies (TT), presence of biomarkers for immunotherapies (IO), and/or therapies that were guideline based (GB) and not associated with a specific biomarker. As much key patient information is only consistently available in free-text medical charts, we implemented a novel natural-language processing (NLP) approach based on deep learning and large language models to accelerate abstraction. Results: A cohort of 1,423 advanced cancer patients met the study criteria. The median age was 66 years, 53% were female, and 82% white. The 3 most tested tumor types were 22% non-small cell lung cancer, 16% colorectal cancer, and 12% breast. Overall, 49% (N=704) of patients had a biomarker result considered actionable for an approved TT or IO. Median (IQR) time-to-treatment initiation post-CGP was 19 (2-70) days. In patients with no actionable TT or IO biomarkers (N=719), 63% were treated with chemotherapy-based regimens, 11% with GB, 17% with unmatched TT, and 8% with unmatched IO. Of patients who had only an actionable TT biomarker (N=287), 18% received matched TT and 13% received GB. 36% of patients with only an actionable IO biomarker (N=317) received matched IO monotherapy. 48% of patients with both actionable TT and IO biomarkers (N=100) received matched TT or IO monotherapy, and 5% received GB. Across all tumor types, patients receiving a TT had better OS compared to patients receiving chemotherapy with 12 months OS (%) of 70.1 (95% CI=64.4 - 76.3) for TT-treated patients, compared to 62.9 (95% CI=58.8 - 67.3) for chemotherapy only. Conclusions: CGP-guided precision therapy use is associated with significantly higher survival in a reflex testing population. A reflex protocol can overcome key barriers to the use and timing of genomic testing to improve access to these life-extending treatment modalities.