Real-world biomarker testing rate and positivity rate in NSCLC in Spain: Prospective Central Lung Cancer Biomarker Testing Registry (LungPath) from the Spanish Society of Pathology (SEAP)

Abstract

AimThe aim of this study was to describe the testing rate and frequency of molecular alterations observed in the Lung Cancer Biomarker Testing Registry (LungPath).MethodsA descriptive study of NSCLC biomarker determinations collected from March 2018 to January 2019, from 38 Spanish hospitals, was carried out. Only adenocarcinoma and not otherwise specified histologies were included for epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1) and programmed death ligand-1 (PD-L1) expression. The testing rate and the positivity rate were calculated. Multivariate logistic regression was used to explore the joint relationship between independent explanatory factors and both testing and positivity rates. Two models were adjusted: one with sample type and histology as independent factors, and the other adding the testing rate or the positivity rate of the other biomarkers.Results3226 patient samples were analysed, where EGFR, ALK, ROS1 and PD-L1 information was collected (a total of 12 904 determinations). Overall, 9118 (71.4%) determinations were finally assessed. EGFR (91.4%) and ALK (80.1%) were the mainly tested biomarkers. Positivity rates for EGFR, ALK, ROS1 and PD-L1 were 13.6%, 3.4%, 2.0% and 49.2%, respectively. Multivariate models showed a lower testing rate for ALK in surgical pieces, fine-needle aspiration or other types of samples versus biopsies.ConclusionsDespite the high testing rate in EGFR and ALK in NSCLC, the real-world evidence obtained from the LungPath demonstrates that ROS1 and PD-L1 were not determined in a significant portion of patients. LungPath provides crucial information to improve the coverage in molecular testing in lung cancer, to monitor the positivity rate and the introduction of new biomarker testing in clinical practice.

Clinical and Economic Impact of ‘ROS1-Testing’ Strategy Compared to a ‘No- ROS1-Testing’ Strategy in Advanced NSCLC in Spain

“…The availability of speci c inhibitors of ROS1 and their clinical bene t should lead to test ROS1 rearrangement simultaneously with EGFR mutation and ALK rearrangement in all advanced stage never/light smokers with squamous cell carcinoma and non-squamous NSCLC (6). However, according to the analysis carried out by Salas et al (2021) (15) in Spain in 2018, despite the relatively high testing rate reported in EGFR and ALK in NSCLC (91.4% and 80.1%, respectively), the real-world evidence obtained from the LungPath registry demonstrates that ROS1 and PD-L1 were not determined in a signi cant portion of patients (56.2% and 58.1%, respectively) (15). Based on these authors, the fact that the determination of ROS1 is not always performed in Spain is probably because the determination in some laboratories is sequential, and there is not enough sample material or samples were of poor quality containing insu cient tumor amount to determine all biomarkers (15).…”

“…Given the incremental importance of ROS1 testing in guiding the treatment of patients with NSCLC and the fact that ROS1 is an underanalyzed biomarker in comparison to ALK or EGFR in Spain (15), the main objective of our study was to assess if testing ROS1 is a cost-effectiveness strategy in Spain and also to raise the awareness of testing ROS1 according the clinical guidelines.…”

“…ROS1 rearrangement should be tested in patients with advanced stage (IIIB-IV) non-squamous NSCLC, regardless of its clinical characteristics and should not be tested in squamous cell carcinoma (except in the context of patients with no or low tobacco exposure and younger than 50 years) (1,7,14). However, although the determination of ROS1 is mandatory according to guidelines, real-world evidence obtained from Lung Cancer Biomarker Testing Registry (LungPath) show that ROS1 fusions were not determined in almost half of the samples of patients with NSCLC (testing rate: 58.1%) (15). According to the Thoracic Tumor Registry (TTR), an observational study also conducted in Spanish hospitals (up to the year 2018), showed even lower ROS1 tests (testing rate [with FISH]: 11.6%]) (16).…”

“…According to the Thoracic Tumor Registry (TTR), an observational study also conducted in Spanish hospitals (up to the year 2018), showed even lower ROS1 tests (testing rate [with FISH]: 11.6%]) (16). This low rate of ROS1 testing may be due to the low prevalence of ROS1 rearrangements in patients with NSCLC that could discourage its determination in some centers, also conditioned by also conditioned by limited diagnostic and/or sampling resources (1,6,15). Essentially, there are three methodological approaches to detecting ROS1 rearrangements: immunohistochemistry (IHC), cytogenetic techniques (particularly uorescent in situ hybridization [FISH], and molecular techniques such as real-time polymerase chain reaction (RT-PCR) or next-generation sequencing (NGS) (1,17).…”

Liquid Biopsy for Biomarker Testing in Non-Small Cell Lung Cancer: A European Perspective

“…Assuming a conservative estimate of 80% of NSCLC patients (all stages) presenting with advanced-stage disease, annually, these percentages would translate to approximately 14,000, 4800, and 19,400 patients in Italy, Spain, and Germany, respectively. In the Spanish Lung Cancer Biomarker Testing Registry study, ALK was not tested in 20% of cases, and ROS1 was not tested in over 40% of cases [23]. The situation is similar in the USA, as shown by a recent study by the MYLUNG Consortium TM , which demonstrated that most patients (90%) received testing for at least one out of five biomarkers (EGFR, ALK, ROS1, BRAF, and PD-L1) prior to first-line therapy, whereas less than half had testing for all five [24].…”