Prognostic Factor Evaluation for Clinical Outcomes in HER2-Mutant NSCLC
Author(s)
Heiko Zettl, PhD1, Lorenz Uhlmann, PhD2, Stephan Herbertz, PhD1, Emma Tyas, MSc3, Neil Roskell, MSc4.
1Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany, 2Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany, 3Lumanity, Sheffield, United Kingdom, 4Lumanity, Manchester, United Kingdom.
1Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany, 2Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany, 3Lumanity, Sheffield, United Kingdom, 4Lumanity, Manchester, United Kingdom.
OBJECTIVES: A targeted literature review found that due to a sparsity of evidence, it is challenging to identify prognostic factors of clinical outcomes in the HER2-mutant non-small-cell lung cancer (HER2m NSCLC) setting. This study aimed to identify prognostic factors (PFs) and potential treatment effect modifiers (TEMs) that influence clinical outcomes in HER2m NSCLC by seeking clinical opinion and exploring patient-level data relationships in a relevant clinical trial (Beamion LUNG-1).
METHODS: Clinical experts were surveyed to identify and rank patient demographics and disease characteristics based on their clinical relevance, specifically in terms of their impact on the efficacy and safety outcomes as PFs or TEMs. Univariate and multivariable exploratory regression analyses of the Beamion LUNG-1 clinical trial patient-level data were conducted to analyse PFs for several outcomes, including overall response rate (ORR) and Grade 3+ adverse events (AEs).
RESULTS: Most clinical experts (89%) expected that specific PFs and TEMs would differ between efficacy and safety outcomes. Mutation in the tyrosine kinase domain, tumour mutation status (YVMA), histology, Eastern Cooperative Oncology Group (ECOG) performance status, and prior lines of therapy were among the highest ranked clinically relevant variables for efficacy endpoints. For safety endpoints, renal function, hepatic function, age, ECOG performance status, and prior lines of therapy were ranked highest. Patient-level data analyses exploring PFs in the Beamion LUNG-1 trial data were consistent with the clinical expert feedback for ORR and Grade 3+ AEs, acknowledging sample size/statistical power limitations.
CONCLUSIONS: This research has identified important patient characteristics that should be considered when forming comparisons and conclusions from clinical study results in HER2m NSCLC. The PF and TEM characteristics influencing outcomes for HER2m NSCLC are likely to differ between efficacy and safety endpoints.
METHODS: Clinical experts were surveyed to identify and rank patient demographics and disease characteristics based on their clinical relevance, specifically in terms of their impact on the efficacy and safety outcomes as PFs or TEMs. Univariate and multivariable exploratory regression analyses of the Beamion LUNG-1 clinical trial patient-level data were conducted to analyse PFs for several outcomes, including overall response rate (ORR) and Grade 3+ adverse events (AEs).
RESULTS: Most clinical experts (89%) expected that specific PFs and TEMs would differ between efficacy and safety outcomes. Mutation in the tyrosine kinase domain, tumour mutation status (YVMA), histology, Eastern Cooperative Oncology Group (ECOG) performance status, and prior lines of therapy were among the highest ranked clinically relevant variables for efficacy endpoints. For safety endpoints, renal function, hepatic function, age, ECOG performance status, and prior lines of therapy were ranked highest. Patient-level data analyses exploring PFs in the Beamion LUNG-1 trial data were consistent with the clinical expert feedback for ORR and Grade 3+ AEs, acknowledging sample size/statistical power limitations.
CONCLUSIONS: This research has identified important patient characteristics that should be considered when forming comparisons and conclusions from clinical study results in HER2m NSCLC. The PF and TEM characteristics influencing outcomes for HER2m NSCLC are likely to differ between efficacy and safety endpoints.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
CO191
Topic
Clinical Outcomes, Health Technology Assessment, Methodological & Statistical Research
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
Oncology