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ObjectivesBiomarker testing is indispensable for the implementation of precision medicine (PM) in oncology. The aim of this study was to assess the value of biomarker testing from a holistic perspective based on the example of advanced non-small cell lung cancer (aNSCLC).Materials and methodsA partitioned survival model was populated with data from pivotal clinical trials of first-line treatments in aNSCLC. Three testing scenarios were considered; “no biomarker testing” encompassing chemotherapy treatment, “sequential testing” for EGFR and ALK encompassing treatment with targeted- or chemotherapy, and “multigene testing” covering EGFR, ALK, ROS1, BRAF, NTRK, MET, RET and encompassing treatment with targeted- or immuno(chemo)therapy. Analyses of health outcomes and costs were run for nine countries (Australia, Brazil, China, Germany, Japan, Poland, South Africa, Turkey, United States). A 1-year and 5-year time horizon was applied. Information on test accuracy was combined with country-specific information on epidemiology and unit costs.ResultsCompared to the no-testing scenario, survival improved and treatment-related adverse events decreased with increased testing. Five-year survival increased from 2% to 5–7% and to 13–19% with sequential testing and multigene testing, respectively. The highest survival gains were observed in East Asia due to a higher local prevalence of targetable mutations. Overall costs increased with increased testing in all countries. Although costs for testing and medicines increased, costs for treatment of adverse events and end-of-life care decreased throughout all years. Non-health care costs (sick leave and disability pension payments) decreased during the first year but increased over a 5-year horizon.ConclusionThe broad use of biomarker testing and PM in aNSCLC leads to more efficient treatment assignment and improves health outcomes for patients globally, in particular prolonged progression-free disease phase and overall survival. These health gains require investment in biomarker testing and medicines. While costs for testing and medicines would initially increase, cost decreases for other medical services and non-health care costs may partly offset the cost increases.

Background: Companion diagnostic (CDx) testing for patients with advanced non‐small cell lung cancer (aNSCLC) identifies patients more likely to benefit from biomarker‐driven treatments. Methods: Patients with nonsquamous cell (non‐Sq) aNSCLC from the Flatiron Health database (diagnosed January 1, 2011–May 31, 2018) who had CDx testing were compared with those who had no reported evidence of testing. The association between CDx testing and overall survival was evaluated by unadjusted and adjusted Cox proportional hazards regression models. Logistic regression analysis identified characteristics associated with CDx testing. The revised modified Lung Cancer Prognostic Index and other factors identified a priori were included in the adjusted models. Results: A total of 17,555 patients with non‐Sq aNSCLC (CDx, n = 14,732; no CDx, n = 2,823) with mean ± SD age of 67.2 ± 10.0 years were included. Most were insured (91.7%) and white (67.1%). Asian patients and those who were never‐smokers were more likely to undergo CDx testing. Those with CDx testing lived longer than those without (median [95% confidence interval (CI)] survival, 13.04 [12.62–13.40] vs. 6.01 [5.72–6.24] months) and had a decreased mortality risk (adjusted hazard ratio [95% CI], 0.72 [0.69–0.76]). A survival advantage was also seen for patients with CDx testing who received biomarker‐driven first‐line therapy. Conclusion: Patients with non‐Sq aNSCLC who had CDx testing had a greater survival benefit than those without, supporting broader use of CDx testing in routine clinical practice to identify patients more likely to benefit from precision medicine. Implications for Practice: Companion diagnostic (CDx) testing coupled with biomarker‐driven treatment offers a greater survival benefit for patients with advanced non‐small cell lung cancer (aNSCLC). In this study, patients with nonsquamous aNSCLC from Flatiron Health, a large, real‐world oncology database, with CDx testing had a reduced mortality risk and lived longer than patients without reported evidence of CDx testing; those who received biomarker‐driven therapy as their first line of treatment were likely to survive three times longer than those who did not. These results demonstrate the clinical utility of CDx testing as the first step in treating nonsquamous aNSCLC in real‐world clinical practice. Improved diagnostic and treatment approaches are needed for patients with non‐small cell lung cancer. This article evaluates the testing patterns and outcomes associated with overall companion diagnostic testing in real‐world clinical practice. [ABSTRACT FROM AUTHOR]

Background: Approximately half of ovarian tumors have defects within the homologous recombination repair pathway. Tumors carrying pathogenic variants (PVs) in BRCA1/BRCA2 are more likely to respond to poly-ADP ribose polymerase (PARP) inhibitor treatment. Large rearrangements (LRs) are a challenging class of variants to identify and characterize in tumor specimens and may therefore be underreported. This study describes the prevalence of pathogenic BRCA1/BRCA2 LRs in ovarian tumors and discusses the importance of their identification using a comprehensive testing strategy., Methods: Sequencing and LR analyses of BRCA1/BRCA2 were conducted in 20 692 ovarian tumors received between March 18, 2016 and February 14, 2023 for MyChoice CDx testing. MyChoice CDx uses NGS dosage analysis to detect LRs in BRCA1/BRCA2 genes using dense tiling throughout the coding regions and limited flanking regions., Results: Of the 2217 PVs detected, 6.3% (N = 140) were LRs. Overall, 0.67% of tumors analyzed carried a pathogenic LR. The majority of detected LRs were deletions (89.3%), followed by complex LRs (5.7%), duplications (4.3%), and retroelement insertions (0.7%). Notably, 25% of detected LRs encompassed a single or partial single exon. This study identified 84 unique LRs, 2 samples each carried 2 unique LRs in the same gene. We identified 17 LRs that occurred in multiple samples, some of which were specific to certain ancestries. Several cases presented here illustrate the intricacies involved in characterizing LRs, particularly when multiple events occur within the same gene., Conclusions: Over 6% of PVs detected in the ovarian tumors analyzed were LRs. It is imperative for laboratories to utilize testing methodologies that will accurately detect LRs at a single exon resolution to optimize the identification of patients who may benefit from PARP inhibitor treatment., (© 2023 Myriad Genetics, Inc and Astrazenca. Genes, Chromosomes and Cancer published by Wiley Periodicals LLC.)

Objectives: Biomarker testing is indispensable for the implementation of precision medicine (PM) in oncology. The aim of this study was to assess the value of biomarker testing from a holistic perspective based on the example of advanced non-small cell lung cancer (aNSCLC)., Materials and Methods: A partitioned survival model was populated with data from pivotal clinical trials of first-line treatments in aNSCLC. Three testing scenarios were considered; "no biomarker testing" encompassing chemotherapy treatment, "sequential testing" for EGFR and ALK encompassing treatment with targeted- or chemotherapy, and "multigene testing" covering EGFR, ALK, ROS1, BRAF, NTRK, MET, RET and encompassing treatment with targeted- or immuno(chemo)therapy. Analyses of health outcomes and costs were run for nine countries (Australia, Brazil, China, Germany, Japan, Poland, South Africa, Turkey, United States). A 1-year and 5-year time horizon was applied. Information on test accuracy was combined with country-specific information on epidemiology and unit costs., Results: Compared to the no-testing scenario, survival improved and treatment-related adverse events decreased with increased testing. Five-year survival increased from 2% to 5-7% and to 13-19% with sequential testing and multigene testing, respectively. The highest survival gains were observed in East Asia due to a higher local prevalence of targetable mutations. Overall costs increased with increased testing in all countries. Although costs for testing and medicines increased, costs for treatment of adverse events and end-of-life care decreased throughout all years. Non-health care costs (sick leave and disability pension payments) decreased during the first year but increased over a 5-year horizon., Conclusion: The broad use of biomarker testing and PM in aNSCLC leads to more efficient treatment assignment and improves health outcomes for patients globally, in particular prolonged progression-free disease phase and overall survival. These health gains require investment in biomarker testing and medicines. While costs for testing and medicines would initially increase, cost decreases for other medical services and non-health care costs may partly offset the cost increases., Competing Interests: TH, CM, and PL were employed by IHE, an independent research organization receiving funding from both public and private sector organizations, and reported institutional fees from Novartis to IHE for the preparation of this study., (Copyright © 2023 Hofmarcher, Malmberg and Lindgren.)

Aims: To present a generalized model to evaluate health and economic outcomes of targeted drug therapies and associated companion diagnostic tests with two applications. Method: An analytical model and derivatives applied to a nonlinear equation representing the costs and benefits of targeted therapy and associated companion diagnostics is developed. Economic analysis is then applied to a breast and colorectal cancer application with a multiparameter sensitivity analysis. Results: The generalized model readily facilitates trade-off analysis between, for example, alternative diagnostic test strategy cost and performance, and accounts for alternative therapy costs and benefits. Example applications demonstrate test performance and therapy costs and benefits are generally more critical parameters relative to diagnostic test cost. Conclusion: While obtaining accurate data on therapy cost and benefits, test performance remains a key challenge in these analyses, the model presents key trade-offs and priorities for research to obtain more accurate clinical and economic information. [ABSTRACT FROM AUTHOR]