A comprehensive real-world analysis of advanced non-small cell lung cancer (NSCLC) patients has revealed stark disparities in survival outcomes and treatment costs based on tumor biomarker status, underscoring the urgent need for improved therapeutic options for patients without targetable mutations.
The study, led by Juanyi Tan, MPH, and published in JAMA Network Open, analyzed data from 26,635 adults diagnosed with NSCLC between 2016 and 2022 using the Flatiron Health database. All patients underwent biomarker testing and received at least one line of therapy, with median follow-up extending through September 2023.
Survival Outcomes Vary Dramatically by Biomarker Status
The research demonstrated significant survival advantages for patients harboring specific driver mutations. Patients with ALK rearrangements achieved the longest median overall survival at nearly 40 months, followed by those with EGFR mutations at 27 months, and BRAF variations at approximately 19 months. In stark contrast, patients without driver alterations—stratified by PD-L1 status—experienced considerably shorter survival, ranging from about 12 to 16 months.
"It was a pretty dismal prognosis to be diagnosed with late stage [NSCLC] a decade ago, but in the past few years, biomarker directive therapy has really changed everything we're able for both early stage and advanced stage," said Alia Lynch, PharmD, BCOP, ambulatory clinical pharmacist at UVA Health in Charlottesville, Virginia. "Targeting genetic mutations can change the course of treatment for these patients, and we're seeing better survival, which further underscores the outcomes for these patients."
Cost Analysis Reveals Economic Burden Disparities
The economic analysis revealed substantial variations in treatment costs across biomarker groups. The average cost to treat a patient for one year was approximately $120,000, rising to about $183,000 for two years. However, the "cost per survivor"—a metric calculating the expense to keep one person alive for a specified period—was consistently higher in patients without driver alterations.
The study found it cost approximately $500,000 to keep one patient with low PD-L1 expression alive for two years, compared with about $363,000 for a patient with an ALK rearrangement. Patients with EGFR variations incurred the highest one-year medication costs, largely attributed to maintenance therapy with newer agents such as osimertinib (Tagrisso).
Testing Gaps Persist in Community Settings
Despite the clear clinical benefits of biomarker testing, significant implementation gaps remain in community oncology practices. According to Melody Chang, RPH, MBA, BCOP, vice president of Pharmacy Operations for the American Oncology Network, biomarker testing rates in community settings often fall short of guideline recommendations due to limited resource access.
In patients with NSCLC in community settings, 83% had at least one biomarker tested; however, only 37% had all nine recommended biomarkers tested. More concerning, only 35.9% of patients with positive biomarker mutations received indicated therapy, and 10.1% received treatments not approved for their specific mutation.
Guidelines Emphasize Comprehensive Testing
Current guidelines strongly advocate for comprehensive biomarker testing. The 2018 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) joint guideline and the National Comprehensive Cancer Network (NCCN) 2025 guidelines recommend molecular testing for all patients with advanced non-squamous NSCLC, with a preference for comprehensive next-generation sequencing (NGS) panels.
NGS has revolutionized biomarker testing by enabling massive parallel sequencing of multiple genes simultaneously to detect mutations, fusions, and copy number alterations. Unlike single-gene testing, NGS provides a more comprehensive view of the genetic landscape and is better at detecting complex mutations and fusions.
Pharmacists Emerge as Key Players in Precision Medicine
The study highlights the growing role of oncology pharmacists in biomarker-driven care. "Pharmacists can play a big role in precision care moving forward," explained Chang. "Why? Because we're the experts of medicines. We know resistance patterns, drug reactions, and are trained to pay attention to critical clinical details. That's exactly what's needed when interpreting the complex genomic report."
Pharmacists are increasingly supporting reflex NGS order sets, leading updates to clinical pathways as new biomarkers and therapies emerge, flagging actionable mutations, and helping interpret complex genomic reports. They also assist with prior authorizations, track testing metrics, and facilitate multidisciplinary collaboration through virtual tumor boards.
Implications for Future Treatment Development
The research represents the first large-scale real-world evaluation of both survival and cost metrics across NSCLC biomarker subtypes. "Medication cost per 1-year or 2-year survivor for patients without driver alterations was consistently higher than those with driver alterations, indicating the need to develop cheaper or more effective medications for these patients," the authors concluded.
The Community Oncology Alliance emphasized the critical importance of biomarker testing in an official statement: "Biomarker testing is pivotal in modern medicine; personalizing cancer treatment testing helps identify specific biological markers in a patient's tumor, guidance selection of most effective therapies. By ensuring that patients receive proper chemotherapy, biologic or biosimilar treatment, biomarker testing improves outcomes, it supports broader access to life saving medications, making advanced care more affordable and equitable."
The findings underscore the urgent need for continued investment in developing more effective and affordable treatments for NSCLC patients without targetable driver mutations, who currently face both poorer outcomes and higher per-survivor treatment costs.
