Abstract 5976: Importance of molecular diagnostic testing preliminary to personalized therapy in NSCLC patients
Authors: Wiley Maxwell Turner, Raja Flores, Matthew Untalan, Stephanie Tuminello, Emanuela Taioli
Journal: Cancer Research (2025)

Abstract Background: Personalized medicine, including targeted and immunotherapy, has substantially changed the landscape of non-small cell lung cancer (NSCLC). About 30% of NSCLC tumors have targetable mutations, like EGFR, and about 28% of tumors will have a PD-L1 score or tumor mutation burden high enough to warrant immunotherapy; a molecular test prior to therapy assesses eligibility. However, the congruence between testing and treatment, and the effect of treatment without testing on outcomes have yet to be studied. Methods: Surveillance, Epidemiology and End Results-Medicare linked data was queried for NSCLC patients diagnosed from 2013 (the first year that standard guidelines for molecular testing in lung cancer were available) to 2015 age &amp;gt; 66 years, stage &amp;gt; II with continuous Part A and B and no Part C coverage 1 year prior to 6 months post-diagnosis, and continuous part D coverage for 6 months after diagnosis. Patients treated with targeted therapy: EGFR, ALK1, KRAS, or BRAF; or immunotherapy: CTLA, PD1; were selected for. Patients with a claim for a molecular diagnostic test within 6 months after cancer diagnosis were defined as tested. Demographic and clinical characteristics of those receiving vs not receiving a molecular test were compared, and a multivariable Cox proportional hazards regression was used to assess the association of overall survival with receipt of molecular diagnostic testing, adjusting for sex, race, age, histology, and stage. Results: There were 911 NSCLC patients treated with a personalized therapy, of which 513 (56.3%) had received prior molecular testing. Black patients were less likely than white patients to receive molecular testing (36.4% vs 59.9%; p&amp;lt;0.001). Molecular testing was significantly more frequent in patients with fewer comorbidities (p&amp;lt;0.001), adenocarcinoma (p=0.004), tumors in the lower lobe (p=0.037) or diagnosed at a later stage (p=0.026). Only 39.9% of patients receiving EGFR inhibitors were initially tested for an EGFR mutation. Overall, among NSCLC patients treated with personalized therapy, untested patients were at increased mortality risk compared to molecularly tested patients (median survival time 8.22 vs 12.79 months, p=0.024). After adjustment, untested patients had a significantly higher mortality risk compared to tested patients (HRadj [hazard ratio]: 1.22; 95% CI [confidence interval]: 1.05-1.41). Conclusions: Although based on claims data, significant incongruence between receipt molecular testing and personalized therapies exists, with only about half of treated patients having had an appropriate molecular diagnostic workup. This could explain, in part, the higher mortality among treated patients who did not undergo testing. Before expanding personalized therapies, studies should examine whether adequate testing is being coupled with these treatments, and outcomes in non-tested patients. Citation Format: Wiley Maxwell Turner, Raja Flores, Matthew Untalan, Stephanie Tuminello, Emanuela Taioli. Importance of molecular diagnostic testing preliminary to personalized therapy in NSCLC patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5976.