Comprehensive genomic profiling of 30,000 consecutive solid tumors

Purpose Tissue-based comprehensive genomic profiling (CGP) is increasingly utilized for treatment selection in patients with advanced solid tumors, however real-world tissue availability may limit widespread implementation. Here we established real-world CGP tissue availability and assessed CGP performance on consecutively received samples. Patients and Method Post-hoc, non-prespecified analysis of 32,048 consecutive tumor tissue samples received for StrataNGS, a multiplex PCR based-CGP (PCR-CGP) test, as part of an ongoing observational trial ([NCT03061305][1]). Tumor tissue sample characteristics and PCR-CGP performance were assessed across all tested tumor samples, including exception samples not meeting minimum input requirements (<20% tumor content [TC], <2mm2 tumor surface area [TSA], DNA or RNA yield <1ng/ul, or specimen age >5yrs). Tests reporting at least one prioritized alteration or meeting all sequencing QC metrics (and ≥20% TC) were considered successful. For prostate carcinoma and lung adenocarcinoma, tests reporting at least one actionable/informative alteration or those meeting all sequencing QC metrics (and ≥20% TC) were considered actionable. Results PCR-CGP was attempted in 31,165 of 32,048 (97.2%) consecutively received solid tumor tissue samples. Among the 31,165 tested samples, 10.7% had low (<20%) tumor content (TC) and 58.4% were small (<25mm2 TSA), highlighting the challenging nature of samples received for CGP. Of the 31,101 samples evaluable for input requirements, 8,079 (26.0%) were exceptions not meeting requirements. However, 94.2% of the 31,101 tested samples were successfully reported, including 80.6% of exception samples. Importantly, 80.6% of 1,344 tested prostate carcinomas and 87.8% of 1,144 tested lung adenocarcinomas yielded results informing treatment selection. Conclusion Most real-world tumor tissue samples from patients with advanced cancer desiring CGP are limited, requiring optimized CGP approaches to produce meaningful results. An optimized PCR-CGP test, coupled with an inclusive exception testing policy, delivered reportable results for >94% of samples, potentially expanding the proportion of CGP-testable patients, and thus the impact of biomarker-guided targeted and immunotherapies. ### Competing Interest Statement Drs. Tomlins, Hovelson, Falkner, Hipp, Lazo de la Vega, Vakil, Rhodes, Kwiatkowski; and Drewery, Fischer, Mitchell, Reeder, Siddiqui, Vakil, and Johnson are/were equity holders and/or employees of Strata Oncology. Drs. Tomlins and Rhodes, and Johnson are named as co-inventors on a patent issued to Strata Oncology related to MSI status assessment. Drs. Tomlins and Rhodes are named as co-inventors and are included in royalty streams for a patent issued to the University of Michigan regarding ETS fusions in prostate cancer that has been licensed to Hologic/Gen-Probe (sublicensed to Ventana Medical Systems) and LynxDx. They are equity holders in Javelin Oncology. Dr. Tomlins previously served as a consultant to Strata Oncology and has consulted for Astellas/Medivation and Janssen. He has received research (to University of Michigan) funding from Astellas and has received travel support from the Prostate Cancer Foundation. Dr. Burkard reports receiving research funding from Abbvie, Genentech, Puma Biotechnology, Arcus Biosciences, Apollomics, and Loxo Oncology. Dr. Matrana reports receiving fees for serving on the speakers bureau from Pfizer, Janssen, Astellas, AstraZeneca Eisai Pharmaceuticals, Bristol-Myers Squibb, Genentech, SirTex, Merck and as a consultant from AstraZeneca. Dr. Yang reports receiving fees for serving on the advisory board from AstraZeneca, Bayer, Clovis Oncology, and for receiving research support from Eli Lilly and Puma Biotechnology. Dr. Parsons reports receiving fees for serving on the speakers bureau and advisory board from Amgen and Celgene, and for research funding from the Wisconsin Idea Grant, Gundersen Medical Foundation. Dr. Thompson reports receiving consulting fees from Syapse Precision Medicine Council, Elsevier ClinicalPath, Adaptive, UpToDate, GlaxoSmithKline, Takeda, Celgene, Doximity, and institutional research funding from Abbvie, Bristol-Myers Squibb, CRAB CTC, Denovo, Hoosier Research Network, Eli Lilly, LynxBio, Takeda, and TG Therapeutics. Dr. Edenfield reports receiving consulting fees from Chimerix. Drs. Dees, Anderson, Suga, Burkard, Matrana, and Yang receive fees for serving on the Strata Oncology Clinical Advisory Board. The remaining authors have no disclosures. ### Clinical Trial NCT03061305 ### Funding Statement The Strata Trial and analyses presented in this article were sponsored by Strata Oncology (Ann Arbor, MI). Authors who are employed by the study sponsor Strata Oncology were involved in the design and conduct of the study: collection, management, analysis, and interpretation of the data; preparation of the manuscript; and the decision to submit the manuscript for publication. ### 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: The Strata Trial was approved by Advarra IRB All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. 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 and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes : De-identified subject and molecular data is made available to all Strata Trial partnered institutions. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT03061305&atom=%2Fmedrxiv%2Fearly%2F2020%2F11%2F22%2F2020.11.19.20233866.atom