Abstract
Improved outcomes from reflex comprehensive genomic profiling-guided precision therapeutic selection across a major US healthcare system.
Author
person
Brian Piening
Earle A. Chiles Research Institute at Robert W. Franz Cancer Center, Providence Cancer Institute, Portland, OR
info_outline
Brian Piening, Bela Bapat, Roshanthi K. Weerasinghe, Ryan Meng, Alexa K. Dowdell, Shu-Ching Chang, Ann Vita, Cliff Wong, Robert Tinn, Lauren Harold, Brock Schroeder, Hoifung Poon, Phillip G. Febbo, Carlo Bruno Bifulco
Full text
Authors
person
Brian Piening
Earle A. Chiles Research Institute at Robert W. Franz Cancer Center, Providence Cancer Institute, Portland, OR
info_outline
Brian Piening, Bela Bapat, Roshanthi K. Weerasinghe, Ryan Meng, Alexa K. Dowdell, Shu-Ching Chang, Ann Vita, Cliff Wong, Robert Tinn, Lauren Harold, Brock Schroeder, Hoifung Poon, Phillip G. Febbo, Carlo Bruno Bifulco
Organizations
Earle A. Chiles Research Institute at Robert W. Franz Cancer Center, Providence Cancer Institute, Portland, OR, Illumina, Inc., San Diego, CA, Health Research Accelerator, Providence Health, Portland, OR, Medical Data Research Center, Providence Health, Portland, OR, Microsoft, Redmond, WA, Microsoft Research, Redmond, WA, Earle A. Chiles Research Institute, Portland, OR
Abstract Disclosures
Research Funding
Pharmaceutical/Biotech Company
Illumina, Providence Foundation of Oregon
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.
8 organizations
3 drugs
6 targets
Organization
Providence Cancer InstituteOrganization
Illumina, Inc.Organization
Health Research AcceleratorOrganization
Providence Health/St John Cancer InstituteOrganization
Medical Data Research CenterOrganization
Microsoft ResearchDrug
CisplatinDrug
immunotherapiesTarget
chemotherapyTarget
immunotherapiesTarget
biomarkersTarget
genomic profilingTarget
targeted therapiesTarget
pan-cancer indications