Widespread adoption of precision anticancer therapies after implementation of pathologist-directed comprehensive genomic profiling across a large US health system

Precision therapies and immunotherapies have revolutionized cancer care, resulting in significant gains in patient survival across tumor types. Despite this transformation in care, there is variability in the utilization of tumor molecular profiling. To standardize testing, we designed a pathologist-directed test ordering system at time of diagnosis utilizing a 523-gene DNA/RNA hybrid comprehensive genomic profiling (CGP) panel. We assessed actionability rates, therapy choices, and outcomes among 3,216 patients. 49% of cases had at least one actionable genomic biomarker-driven (GBD) approved and/or guideline-recommended targeted or immunotherapy and 53% of patients would have been eligible for a precision therapy clinical trial from three large basket trials. When assessing CGP versus an insilico 50 gene panel, 67% of tumors compared to 33% harbored actionable alterations. Among patients with 6-months or more of follow-up, over 52% received a targeted therapy or immunotherapy, versus 32% that received conventional chemotherapy alone, a phenomenon not previously observed. Statement of Significance This study represents the first report where precision therapies (targeted and immunotherapy) have overtaken traditional cytotoxic treatments in the routine community-based care of advanced cancer patients, resulting in better overall survival. This represents an important milestone in the evolution and adoption of precision oncology and highlights the importance of CGP. ### Competing Interest Statement All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: BP and CBB acknowledge institutional financial support from Illumina, Inc for the submitted work; BB and BS are employees and stockholders of Illumina, Inc; CW and HP are employees of Microsoft; BP has received research grants from Loxo@Lilly and Shimadzu Scientific; RL has grants and/or contracts with Bristol Myers Squibb, Incyte and AstraZeneca; BP has been paid for consulting Loxo@Lilly and Optum; CBB has been paid for consulting Sanofi, Agilent, Roche, and Incendia; RL has been paid for consulting at Bristol Myers Squibb, Merck, Vir, AstraZeneca, and CDR-Life; CBB has received payment or honoraria for a presentation from Abcam; CBB has received support from Illumina for travel; RL has received travel support from Bristol Myers Squibb; CBB has patents US20180322632A1 and US20200388033A1 planned and/or issued; WU participates on a Data Safety Monitoring board for AstraZeneca; CBB participates on Data Safety Monitoring boards for PrimeVax, BioAI and Lunaphore; RL participates on a Data Safety Monitoring board for Incyte; CBB has PrimeVax stock options; BP has been gifted early instrument access from Lunaphore; RL has been gifted materials and/or services from Celldex, Ubivac, Incyte, and Clinigen; no other relationships or activities that could appear to have influenced the submitted work. ### Funding Statement This study was funded in part by Illumina. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee/IRB of Providence gave ethical approval for this work. All research was performed under protocol 201900048 "Effect of Automatic Reflex Genomics Testing on Clinical and Economic Outcomes in Cancer" approved by Providence IRB. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes