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Despite clear clinical guidelines recommending biomarker testing to guide targeted therapies in advanced cancers, a recent cohort study reveals suboptimal testing rates, though these are increasing over time. Importantly, comprehensive genomic profiling (CGP) did not result in higher overall health care costs during first-line therapy compared to non-CGP testing, while showing an increased likelihood of patients receiving appropriate targeted treatments.1
These findings, published in JAMA Network Open, underscore the critical need to improve access to biomarker testing to optimize patient outcomes.
The retrospective study, leveraging claims data from 26,311 adults with newly diagnosed advanced breast, colorectal, gastric, non–small cell lung, ovarian, and pancreatic cancers, highlights a persistent gap between guideline recommendations and clinical practice. While 35% of patients had evidence of molecular testing before first-line therapy, this figure varied significantly by cancer type, ranging from a low of 17% in ovarian cancer to a high of 45% in non–small cell lung cancer (NSCLC). Although testing rates showed an upward trend from 32% in 2018 to 39% in 2021 to 2022, the overall proportion remains below guideline recommendations.
CGP Boosts Targeted Therapy Uptake
One of the study’s key findings is the association between CGP testing and increased receipt of targeted therapy. Patients with NSCLC and colorectal cancer (CRC) who underwent CGP testing were significantly more likely to receive targeted therapy during first-line treatment compared with those who received non-CGP testing or no testing. For NSCLC, the odds of receiving targeted therapy were 1.57 times higher for CGP-tested patients compared to those with non-CGP testing (P <.001). Similarly for CRC, CGP-tested patients had 2.34 times higher odds of receiving targeted therapy compared to the non-CGP group (P <.001). This suggests that comprehensive profiling offers a tangible benefit in identifying actionable mutations, thereby enabling more patients to access precision medicine.
Cost Neutrality and Clinical Implications
A crucial aspect addressed by the study is the economic impact of CGP. Analysis of per-patient per-month (PPPM) costs during first-line therapy revealed no statistically significant difference in all-cause health care costs between patients who received CGP testing and those who received non-CGP testing across all evaluated cancer types. For instance, the cost ratio for breast cancer was 1.03 (P =.63), for CRC 0.98 (P =.71), and for NSCLC 1.06 (P =.054). While both CGP and non-CGP groups generally had higher costs than the no-testing group, this is likely attributed to the downstream costs of targeted therapies, which are often more expensive but also more effective.
The cost neutrality of CGP is a vital consideration for health care systems and payers. Concerns about the expense of advanced genomic testing have sometimes been cited as barriers to wider adoption. This study provides real-world evidence that the initial investment in comprehensive profiling does not translate into a significant increase in overall first-line therapy costs, especially when considering the potential for improved clinical outcomes through optimized treatment selection.
Addressing the Testing Gap
The study underscores a persistent practice gap between clinical guidelines and the actual implementation of biomarker testing. Despite the growing number of FDA-approved biomarker-targeted therapies and their inclusion in standard treatment guidelines, a substantial proportion of patients with advanced cancer are not receiving recommended testing. This is particularly concerning given the well-established survival advantages associated with biomarker-matched targeted therapies.
“A large body of research has demonstrated the value of biomarker testing, especially for NSCLC,” study authors wrote. “Biomarker testing, when completed before first-line therapy, can meaningfully improve outcomes of patients with NSCLC.1,2 National clinical guidelines recommend completing broad molecular profiling during the diagnostic evaluation and before initiation of first-line treatment. Despite this evidence, only 45% of patients with NSCLC had evidence of biomarker testing by the start of first-line therapy.”
One factor often cited as a barrier to CGP is inadequate insurance coverage. However, the study found that testing rates in Medicare Advantage beneficiaries were generally lower or comparable to commercial health plan patients, despite comprehensive genomic profiling being covered.1 This suggests that factors beyond insurance coverage, such as lack of physician awareness, logistical challenges in ordering and processing tests, or delays in obtaining results, may also contribute to suboptimal testing rates.
Future Directions
The study acknowledges limitations inherent in using administrative claims data, such as the inability to capture specific biomarker test results or differentiate between squamous and nonsquamous NSCLC. However, the large cohort size and real-world setting provide valuable insights into current biomarker testing practices and their associated costs and targeted therapy uptake.
Moving forward, interventions are urgently needed to improve biomarker testing rates across all cancer types, especially as more targeted therapies emerge. Healthcare providers should prioritize early and comprehensive genomic profiling for patients with advanced cancers, in line with clinical guidelines. Education initiatives for clinicians, streamlined testing workflows, and improved access to molecular pathology services could all contribute to closing the testing gap. Given the potential for CGP to optimize tissue stewardship, detect genomic signatures like tumor mutational burden, and enhance eligibility for clinical trials, its increased adoption holds significant promise for improving patient outcomes without imposing a substantial additional financial burden.