Key Takeaways A study from The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) suggests all patients with non-small cell lung cancer (NSCLC) should be considered for biomarker testing to ensure they receive optimal precision therapies. The study was recently published in the Journal of Thoracic Oncology and led by Christian Rolfo, MD, PhD, of the OSUCCC – James. Researchers say the global study helps reinforce universal molecular testing as a standard-of-care in lung cancer. COLUMBUS, Ohio – An international study led by The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) suggests all patients with non-small cell lung cancer (NSCLC) should be considered for biomarker testing – or molecular analysis that can identify disease subtypes based on gene and protein alterations – to ensure they receive optimal precision therapies. In what some cancer experts consider a landmark study, the researchers examined over 82,000 NSCLC cases, the largest dataset to date for this disease, and found gene alterations that could be targeted for therapy are present across NSCLC subtypes, age groups, sex and genetic ancestry. “The central message is clear – all patients with NSCLC should be considered for comprehensive biomarker testing, rather than limiting testing to selected histologies,” said Christian Rolfo, MD, PhD, thoracic oncologist and director of Medical Oncology at the OSUCCC – James. Rolfo was the corresponding author of the study, published in the Journal of Thoracic Oncology. “Universal biomarker testing is essential to delivering precision cancer care at scale,” said W. Kimryn Rathmell, MD, PhD, CEO and Director of the OSUCCC – James. “This work exemplifies how our strategy translates discovery into impact for every patient.” Despite the increased availability of biomarker testing, their retrospective analysis of patient data from 2015 to 2021 found that nearly a third of patients with advanced or metastatic non-squamous NSCLC still had not received broad genomic profiling by 2020. As a result, a large proportion of patients lacked a complete molecular tumor profile, thereby missing potential actionable alterations or receiving inappropriate immunotherapy regimens. “Biomarker testing is essential for therapeutic management of patients with NSCLC because it can identify the best targeted therapies,” said Rolfo, also associate director for early-phase clinical trials at the OSUCCC – James. “However, many patients with advanced NSCLC aren’t benefiting from precision oncology. This gap in care has been attributed largely to missed biomarker testing opportunities and is reported in up to nearly 50% of cases.” This study analyzed the distribution of actionable gene alterations across histologic subtypes and demographic subgroups of patients with NSCLC from within the large dataset, aiming to support universal molecular testing for all subtypes and ensure equal access to therapeutics. The study’s findings: An actionable genomic alteration (GA) occurred in 35% of the cases. Among NSCLC subtypes, lung adenocarcinoma and adenosquamous were more commonly associated with actionable GA (45.8% and 40.9%, respectively) as compared with sarcomatoid (29%), not-otherwise-specified (27.6%), large cell (21.1%) and squamous cell (6.5%). Tumor mutation burden (TMB), or the number of gene alterations in tumor DNA – a predictive biomarker for immunotherapy response – was associated with histology for all subtypes. Patients with actionable GAs usually had a low TMB. Notably, the highest frequency of high TMB was associated with large cell lung cancer, which has been observed predominantly in smokers. Differences in TMB levels across histologies and oncogene-driven subgroups might explain the different levels of sensitivity to immunotherapy. While the frequency of cancer gene drivers differs among histologic subtypes, their data underscore the importance of not limiting biomarker testing to only certain forms of NSCLC, such as adenocarcinoma, as has often been the case. In addition to identifying actionable gene alterations, tumor biomarker profiling can uncover other genomic alterations with emerging clinical significance. Researchers confirm sufficient biomarker prevalence across many histological subtypes of NSCLC, providing reassurance that all NSCLC cases should be considered for biomarker workup. “The impact of this paper goes beyond the immediate findings,” said Rolfo. “It helps reinforce universal molecular testing as a standard-of-care principle in lung cancer and opens an important broader discussion about whether lung cancer classification should increasingly incorporate genomic features, potentially informing future World Health Organization nomenclature considerations.” Scientists from institutions in Italy, Spain and elsewhere in the United States were co-authors on this study. To learn more about cancer treatment and clinical trials at the OSUCCC – James, visit cancer.osu.edu or call 1-800-293-5066. Media Contact Mary Ellen Fiorino, Ohio State Wexner Medical Center Media Relations, MaryEllen.Fiorino@osumc.edu