Optimising primary molecular profiling in non-small cell lung cancer

• Published in: PloS one Vol. 19; no. 7; p. e0290939
• Main Authors: Schouten, R D, Schouten, I, Schuurbiers, M M F, van der Noort, V, Damhuis, R A M, van der Heijden, E H F M, Burgers, J A, Barlo, N P, van Lindert, A S R, Maas, K W, van den Brand, J J G, Smit, A A J, van Haarst, J M W, van der Maat, B, Schuuring, E, Blaauwgeers, H, Willems, S M, Monkhorst, K, van den Broek, D, van den Heuvel, M M
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 31.07.2024; Public Library of Science (PLoS)
• Subjects: Adult; Aged; Aged, 80 and over; Analysis; Anaplastic Lymphoma Kinase - genetics; B7-H1 Antigen - genetics; B7-H1 Antigen - metabolism; Biology and Life Sciences; Biomarkers; Biomarkers, Tumor - genetics; Biopsy; Carcinoma, Non-Small-Cell Lung - diagnosis; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Diagnostic systems; DNA fingerprinting; Epidermal growth factor receptors; ErbB Receptors - genetics; Ethylenediaminetetraacetic acid; Female; Gene Expression Profiling - methods; Humans; Lung cancer; Lung cancer, Non-small cell; Lung diseases; Lung Neoplasms - diagnosis; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Male; Medicine and Health Sciences; Middle Aged; Mutation; Netherlands; Non-small cell lung carcinoma; Observational studies; Patients; PD-L1 protein; Pharmaceutical industry; Prospective Studies; Proto-Oncogene Proteins p21(ras) - genetics; Small cell lung carcinoma; Squamous cell carcinoma; Tissues; Tumors; Netherlands; United Kingdom; United States; Switzerland; Basel Switzerland; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0290939

Molecular profiling of NSCLC is essential for optimising treatment decisions, but often incomplete. We assessed the efficacy of protocolised molecular profiling in the current standard-of-care (SoC) in a prospective observational study in the Netherlands and measured the effect of providing standardised diagnostic procedures. We also explored the potential of plasma-based molecular profiling in the primary diagnostic setting. This multi-centre prospective study was designed to explore the performance of current clinical practice during the run-in phase using local SoC tissue profiling procedures. The subsequent phase was designed to investigate the extent to which comprehensive molecular profiling (CMP) can be maximized by protocolising tumour profiling. Successful molecular profiling was defined as completion of at least EGFR and ALK testing. Additionally, PD-L1 tumour proportions scores were explored. Lastly, the additional value of centralised plasma-based testing for EGFR and KRAS mutations using droplet digital PCR was evaluated. Total accrual was 878 patients, 22.0% had squamous cell carcinoma and 78.0% had non-squamous NSCLC. Stage I-III was seen in 54.0%, stage IV in 46.0%. Profiling of EGFR and ALK was performed in 69.9% of 136 patients included in the run-in phase, significantly more than real-world data estimates of 55% (p<0.001). Protocolised molecular profiling increased the rate to 77.0% (p = 0.049). EGFR and ALK profiling rates increased from 77.9% to 82.1% in non-squamous NSCLC and from 43.8% to 57.5% in squamous NSCLC. Plasma-based testing was feasible in 98.4% and identified oncogenic driver mutations in 7.1% of patients for whom tissue profiling was unfeasible. This study shows a high success rate of tissue-based molecular profiling that was significantly improved by a protocolised approach. Tissue-based profiling remains unfeasible for a substantial proportion of patients. Combined analysis of tumour tissue and circulating tumour DNA is a promising approach to allow adequate molecular profiling of more patients.