Biomarker testing in non-small cell lung cancer in routine care: Analysis of the first 3,717 patients in the German prospective, observational, nation-wide CRISP Registry (AIO-TRK-0315)

Griesinger, Frank; Eberhardt, Wilfried; Nusch, Arnd; Reiser, Marcel; Zahn, Mark‐Oliver; Maintz, Christoph; Bernhardt, Christian; Losem, Christoph; Stenzinger, Albrecht; Heukamp, Lukas C.; Büttner, Reinhard; Marschner, Norbert; Jänicke, Martina; Fleitz, A.; Spring, Lisa; Sahlmann, J.; Karatas, Aysun; Hipper, A.; Weichert, Wilko; Heilmann, Monika; Sadjadian, Parvis; Gleiber, Wolfgang; Grah, Christian; Waller, Christiane; Reck, Martin; Rittmeyer, Achim; Christopoulos, Petros; Sebastian, Martin; Thomas, Michael

doi:10.1016/j.lungcan.2020.10.012

Cited by 63 publications

(80 citation statements)

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“…Study sites are encouraged to recruit patients consecutively. Further details on the data collection in the CRISP registry have been published previously [7].…”

Section: Methodsmentioning

confidence: 99%

“…Despite advancements in personalized treatment and precision medicine, the overall five-year survival rate of patients with advanced NSCLC in Germany remains low at 15-21 % [3,4]. The most frequent oncogenic driver mutations are found in the KRAS gene, occurring in 20-40 % of the NSCLC cases in Western populations [5][6][7]. KRAS mutations are more prevalent in Western than in Asian populations, and more frequently found in smokers than in non-smokers [reviewed in 8].…”

Section: Introductionmentioning

confidence: 99%

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KRAS G12C-mutated advanced non-small cell lung cancer: A real-world cohort from the German prospective, observational, nation-wide CRISP Registry (AIO-TRK-0315)

et al. 2021

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After decades of unsuccessful efforts in inhibiting KRAS, promising clinical data targeting the mutation subtype G12C emerge. Since little is known about outcome with standard treatment of patients with G12C mutated non-small cell lung cancer (NSCLC), we analyzed a large, representative, real-world cohort from Germany. Patients and methods: A total of 1039 patients with advanced KRAS-mutant or-wildtype NSCLC without druggable alterations have been recruited in the prospective, observational registry CRISP from 12/2015 to 06/2019

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“…Study sites are encouraged to recruit patients consecutively. Further details on the data collection in the CRISP registry have been published previously [7].…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

KRAS G12C-mutated advanced non-small cell lung cancer: A real-world cohort from the German prospective, observational, nation-wide CRISP Registry (AIO-TRK-0315)

et al. 2021

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“…BRAF and NTRK), which are recommended by national guidelines in some European countries, testing rates may be lower than those for the more established predictive markers (EGFR, ALK, and ROS1). For example, in Germany between 2015 and 2019, BRAF testing rates were 53.0 % versus 72.5 %, 74.5 % and 66.1 % for EGFR, ALK, and ROS1, respectively [67]. As seen with the recent addition of a recommendation for NTRK testing in the ESMO guidelines [6], the biomarker landscape in European countries is rapidly evolving.…”

Section: Uptake Of Biomarker Testing In Europementioning

confidence: 99%

The evolving landscape of biomarker testing for non-small cell lung cancer in Europe

et al. 2021

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The discovery of oncogenic driver mutations rendering non-small cell lung cancer (NSCLC) targetable by smallmolecule inhibitors, and the development of immunotherapies, have revolutionised NSCLC treatment. Today, instead of non-selective chemotherapies, all patients with advanced NSCLC eligible for treatment (and increasing numbers with earlier, less extensive disease) require fast and comprehensive screening of biomarkers for first-line patient selection for targeted therapy, chemotherapy, or immunotherapy (with or without chemotherapy). To avoid unnecessary re-biopsies, biomarker screening before first-line treatment should also include markers that are actionable from second-line onwards; PD-L1 expression testing is also mandatory before initiating treatment.Population differences exist in the frequency of oncogenic driver mutations: EGFR mutations are more frequent in Asia than Europe, whereas the converse is true for KRAS mutations. In addition to approved first-line therapies, a number of emerging therapies are being investigated in clinical trials. Guidelines for biomarker testing vary by country, with the number of actionable targets and the requirement for extensive molecular screening strategies expected to increase. To meet diagnostic demands, rapid screening technologies for singledriver mutations have been implemented. Improvements in DNA-and RNA-based next-generation sequencing

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“… 1 Most frequent are mutations in the epidermal growth factor receptor gene ( EGFR ) occurring in 10%-15% of adenocarcinomas, followed by anaplastic lymphoma kinase gene ( ALK ) fusions in up to 5%. 2 Approximately 25% of these patients present with brain metastases (BM) at the time of diagnosis, which appear, at least in EGFR + tumors, to be associated with a worse prognosis. 3 , 4 , 5 The strategies to treat central nervous system (CNS) involvement in dm-NSCLC are influenced by the increasing availability of targeted drugs with better CNS penetration and antitumor activity than conventional chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

Effect of timing, technique and molecular features on brain control with local therapies in oncogene-driven lung cancer

et al. 2021

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Background The improved efficacy of tyrosine kinase inhibitors (TKI) mandates reappraisal of local therapy (LT) for brain metastases (BM) of oncogene-driven non-small-cell lung cancer (NSCLC). Patients and methods This study included all epidermal growth factor receptor-mutated (EGFR + , n = 108) and anaplastic lymphoma kinase-rearranged (ALK + , n = 33) TKI-naive NSCLC patients diagnosed with BM in the Thoraxklinik Heidelberg between 2009 and 2019. Eighty-seven patients (62%) received early LT, while 54 (38%) received delayed ( n = 34; 24%) or no LT ( n = 20; 14%). LT comprised stereotactic (SRT; n = 40; 34%) or whole-brain radiotherapy (WBRT; n = 77; 66%), while neurosurgical resection was carried out in 19 cases. Results Median overall survival (OS) was 49.1 months for ALK + and 19.5 months for EGFR + patients ( P = 0.001), with similar median intracranial progression-free survival (icPFS) (15.7 versus 14.0 months, respectively; P = 0.80). Despite the larger and more symptomatic BM ( P < 0.001) of patients undergoing early LT, these experienced longer icPFS [hazard ratio (HR) 0.52; P = 0.024], but not OS (HR 1.63; P = 0.12), regardless of the radiotherapy technique (SRT versus WBRT) and number of lesions. High-risk oncogene variants, i.e. non-del19 EGFR mutations and ‘short’ EML4-ALK fusions (mainly variant 3, E6:A20), were associated with earlier intracranial progression (HR 2.97; P = 0.001). The longer icPFS with early LT was also evident in separate analyses of the EGFR + and ALK + subsets. Conclusions Despite preferential use for cases with poor prognostic factors, early LT prolongs the icPFS, but not OS, in TKI-treated EGFR + /ALK + NSCLC. Considering the lack of survival benefit, and the neurocognitive effects of WBRT, patients presenting with polytopic BM may benefit from delaying radiotherapy, or from radiosurgery of multiple or selected lesions. For SRT candidates, the improved tumor control with earlier radiotherapy should be weighed against the potential toxicity and the enhanced intracranial activity of newer TKI. High-risk EGFR / ALK variants are associated with earlier intracranial failure and identify patients who could benefit from more aggressive management.

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Biomarker testing in non-small cell lung cancer in routine care: Analysis of the first 3,717 patients in the German prospective, observational, nation-wide CRISP Registry (AIO-TRK-0315)

Cited by 63 publications

References 32 publications

KRAS G12C-mutated advanced non-small cell lung cancer: A real-world cohort from the German prospective, observational, nation-wide CRISP Registry (AIO-TRK-0315)

KRAS G12C-mutated advanced non-small cell lung cancer: A real-world cohort from the German prospective, observational, nation-wide CRISP Registry (AIO-TRK-0315)

The evolving landscape of biomarker testing for non-small cell lung cancer in Europe

Effect of timing, technique and molecular features on brain control with local therapies in oncogene-driven lung cancer

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