Despite broad implementation of next-generation sequencing (NGS) panel testing, a paucity of data exists defining costs and consequences of NGS panel testing using real-world population-based data. By exploring health-associated costs of NGS panel testing, and outcomes including overall survival (OS) within the Ontario-wide Cancer Targeted Nucleic Acid Evaluation (OCTANE), in the context of a low alteration-treatment match rate, the use of NGS panel testing was associated with increased costs and no detectable survival benefit, similar to short-term findings from the British Columbia's Personalized OncoGenomics programme.
Added outpatient clinic visits (e.g. for trials, treatments and follow-up) were a major driver of cost differences. When stratified by tumour cohorts, variation as observed in survival by subgroup remained significant for biliary tract cancer and ovarian cancer after adjustment for multiple comparisons. Furthermore, patients enroled in OCTANE had more clinical trial enrolment and less death in hospital. The findings are published by Prof. Timothy Hanna of the Division of Cancer Care and Epidemiology, Cancer Research Institute at Queens University in Kingston, ON, Canada and colleagues on 12 February 2024 in the eClinicalMedicine, part of THE LANCET Discovery Science.
To evaluate the clinical utility of tissue-based NGS panel testing, several academic institutions have instituted prospective programmes with longitudinal follow-up. OCTANE was a prospective study in the province of Ontario, Canada from 2016 to 2019 that included 7 academic hospitals to advance NGS panel testing, and data sharing and to create a province-wide repository of biospecimens for future research.
Ontario is a publicly funded, single-payer health care system where broad panel testing for all solid tumours is not reimbursed by the publicly funded healthcare system and private-pay testing is not routinely performed. The main inclusion criteria for OCTANE included patients at least 18 years old, diagnosed with advanced or metastatic solid tumours, with an ECOG performance status of 0–1, with sufficient formalin-fixed archived tumour tissue available for molecular profiling and adequate organ function with a life expectancy of more than 6 months assessed by the investigator.
Patients were required to have archival formalin-fixed paraffin embedded samples for NGS testing as well as blood samples. Patients could not have received more than 2 lines of prior cytotoxic therapy for their recurrent/metastatic disease, except for patients being considered for phase I clinical trials who could be more heavily pretreated.
The study team evaluated the real-world impact on healthcare costs and consequences in terms of OS, trial enrolment and end-of-life quality of care associated with the use of tissue-based NGS testing compared with no use of NGS testing in a public universal health system. Like international experiences, match rates based on alterations in OCTANE was relatively low, in total 17% of patients with actionable mutations, and thus may have limited impact on survival, while still influencing costs and other outcomes.
The authors performed a cost consequence analysis of NGS testing (555 or 161-gene panels) for advanced solid tumours through the OCTANE clinical trial. This is a longitudinal, propensity score-matched retrospective cohort study in Ontario, Canada using linked administrative data. Patients enroled in OCTANE at Princess Margaret Cancer Centre from August 2016 until March 2019 were matched with contemporary patients without large gene panel testing from across Ontario not enroled in OCTANE.
Patients were matched according to 19 patient, disease, and treatment variables. Full 2-year follow-up data was available. Sensitivity analyses considered alternative matched cohorts. Main outcomes were mean per capita costs (2019 Canadian dollars) from a public payer's perspective, OS, clinical trial enrolment and end-of-life quality metrics.
There were 782 OCTANE patients with 782 matched controls. Variables were balanced after matching (standardised difference <0.10). There were higher mean healthcare costs with OCTANE ($79,702 vs. $59,550), mainly due to outpatient and specialist visits. Publicly funded drug costs were less with OCTANE ($20,015 vs. $24,465).
OCTANE enrolment was not associated with improved OS (restricted mean survival time [standard error] 1.50 (±0.03) versus 1.44 (±0.03) years, log-rank p = 0.153), varying by tumour type. In five tumour types with ≥35 OCTANE patients, OS was similar in three (breast, colon, uterus, all p > 0.40), and greater in two (ovary, biliary, both p < 0.05).
OCTANE was associated with greater clinical trial enrolment (25.4% versus 9.5%, p < 0.001) and better end-of-life quality due to less death in hospital (10.2% versus 16.4%, p = 0.003). Results were robust in sensitivity analysis.
This is the first study assessing the impact of NGS panel testing in clinical practice across multiple outcomes by linking the results of genomic profiling with administrative data. However, despite efforts to propensity match cohorts, both the OCTANE and non-OCTANE matched cohorts were enriched to include patients who were younger, predominantly female and from higher income backgrounds that may limit the generalisability of findings.
The authors concluded that they an increase in healthcare costs was associated with multigene panel testing for treatment of advanced cancer. The impact on OS was not significant, but varied across tumour types. OCTANE was associated with greater trial enrolment, lower publicly funded drug costs and fewer in-hospital deaths suggesting important considerations in determining the value of NGS panel testing for advanced cancers that deserve further investigation.
The main advantage of this study is the use of only real-world data related to treatment access and patient care trajectories in a universal healthcare system. The comprehensive evaluation of end-of-life quality assessments across administrative databases enabled to study the impact of NGS panel testing on these variables. This is the first study incorporating these endpoints. Importantly, there was less death in hospital observed in patients included in the OCTANE cohort.
OCTANE patients also had lower publicly funded systemic therapy costs, though increased clinical trial access and greater overall health care costs. These findings provide important perspectives to private and public payers. The fact that OCTANE enrolment was also associated with more clinical trial access as first line of treatment after the index date supports the use of NGS to increase the treatment options according to the study team.
This study was supported by the Institute for Clinical Evaluative Sciences, which is funded by an annual grant from the Ontario Ministry of Health and the Ministry of Long-Term Care.
Reference
Hernando-Calvo A, Nguyen P, Bedard PL, et al. Impact on costs and outcomes of multi-gene panel testing for advanced solid malignancies: a cost-consequence analysis using linked administrative data. eClinicalMedicine; Published 12 February 2024. DOI: https://doi.org/10.1016/j.eclinm.2024.102443