e13727 Background: Literature demonstrates that non-actionable biomarkers (BMs) can co-occur with actionable ones in NSCLC and impact patient outcome. Our research sought to examine oncologists’ perspectives on hierarchy of clinical relevance of established and emerging BMs, their decision framework for managing co-occurring BMs, and how it could play out in future when these non-actionable BM become actionable. Methods: Between November-December 2025, 50 US-based Oncologists from a diverse set of practice settings and experience managing patients with metastatic NSCLC were recruited. They completed a 45-minute one-on-one interview where they shared perspective on their BM-informed treatment philosophy – BM prioritization, treatment algorithm over multiple lines of therapy when co-occurring BM are detected, and how they arrived at those beliefs in the present context. Results: Among the oncologists included in the study, 60% practiced in community settings and 40% in academic settings. Across practice types, the primary factors guiding treatment selection were efficacy, safety, alignment with clinical guidelines and FDA approval. Overall, 92% of respondents (45/49) reported that NCCN guidelines were useful for evidence-based decision-making, including 28% (14/49) who found them extremely helpful. Despite this reliance on guidelines, nearly 60% of responders (29/49) indicated that there is no clearly defined protocol for managing co-occurring BM or reported being unfamiliar/uncertain about available guidance. When presented with a clinical scenario involving co-occurring EGFR and TP53 mutation, 28 oncologists shared their perspectives. Approximately half (15/28) reported they would initiate therapy with an anti-TP53 drug followed by EGFR inhibitor, provided the anti-TP53 drug demonstrated ~20% higher efficacy in comparison to 'historical EGFR inhibitor outcomes in patients with co-occurring EGFR and TP53 mutation’, even if the registrational trial for anti-TP53 drug did not give details on patients with co-occurring mutations, or if such patients were excluded from the trial. Remaining oncologists preferred initiating treatment with an EGFR inhibitor and sequencing anti-TP53 therapy upon progression, citing greater familiarity with EGFR-directed treatments. These perspectives were similarly distributed across community and academic practice settings. Conclusions: This study shows that in the absence of clear regulatory or clinical guidance, treatment decisions for patients with co-occurring BMs may vary widely. While clinicians draw on conferences data and published research, this evidence base is insufficient to ensure consistent care. Our findings underscore the need for coordinated action from researchers, regulators and guideline bodies to establish clear standards of care to improve outcomes for patients with BM-complex disease.
Nair et al. (Thu,) studied this question.