Treatment outcome of atypical EGFR mutations in the German National Network Genomic Medicine Lung Cancer (nNGM)

Janning, Melanie; Süptitz, Juliane; Albers-Leischner, Corinna; Delpy, Pierre; Tufman, Amanda; Velthaus-Rusik, J-L; Reck, Martin; Jung, Andreas; Kauffmann-Guerrero, Diego; Bonzheim, Irina; Brändlein, Stephanie; Hummel, H-D.; Wiesweg, Marcel; Hu, Schildhaus; Stratmann, Jan; Sebastian, Martin; Alt, Jürgen August; Buth, J; Espósito, Irene; Berger, Jeanne-Marie; Tögel, Lars; Saalfeld, Felix C.; Wermke, Martin; Merkelbach‐Bruse, Sabine; Hillmer, Axel M.; Klauschen, Frederick; Bokemeyer, Carsten; Buettner, Reinhard; Wolf, Juergen; Loges, Sonja

doi:10.1016/j.annonc.2022.02.225

Cited by 58 publications

(31 citation statements)

References 32 publications

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“…Uncommon EGFR mutations account for 10%-20% of EGFR mutations in advanced NSCLC and occur in 10%-20% of patients with NSCLC and, with the exception of EGFR exon 20 insertion mutations, generally respond to second- and third-generation EGFR TKIs. 22 , 23 , 24 , 25 Compared with common EGFR mutations, EGFR exon 20 insertion mutations are more common in patients with a smoking history. 26 It would be of interest to explore the role of combination EGFR TKI and anti-angiogenic agents in such a patient population.…”

Section: Discussionmentioning

confidence: 99%

Impact of smoking status on the relative efficacy of the EGFR TKI/angiogenesis inhibitor combination therapy in advanced NSCLC—a systematic review and meta-analysis

et al. 2022

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Section: Discussionmentioning

confidence: 99%

Impact of smoking status on the relative efficacy of the EGFR TKI/angiogenesis inhibitor combination therapy in advanced NSCLC—a systematic review and meta-analysis

et al. 2022

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“…According to the classification of uncommon EGFR mutations followed by Yang et al [ 41 ], we assigned 9.7% (7/72) mutations as class I (point mutations in exon 18, 19, 20, and 21), no mutations as class II (primary p.Thr790Met), and 9.7% (7/72) mutations as class III (exon 20 insertions). However, following a recently published new classification of rare EGFR mutations by Janning et al [ 42 ], we found 55.0% (11/20) group 1 mutations (G719X, S7681, L861Q, and combinations) that enable higher efficacy of EGFR-TKI in comparison to chemotherapy. Another 35.0% (7/20) were classified as group 2 mutations (exon 20 insertions), most of them not TKI responsive.…”

Section: Resultsmentioning

confidence: 59%

Landscape of Genomic Alterations and PD-L1 Expression in Early-Stage Non-Small-Cell Lung Cancer (NSCLC)—A Single Center, Retrospective Observational Study

Stephan-Falkenau

Streubel

Mairinger

et al. 2022

IJMS

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Precision oncology and immunotherapy have revolutionized the treatment of advanced non-small-cell lung cancer (NSCLC). Emerging studies show that targeted therapies are also beneficial for patients with driver alterations such as epidermal growth factor receptor (EGFR) mutations in early-stage NSCLC (stages I–IIIA). Furthermore, patients with elevated programmed death-ligand 1 (PD-L1) expression appear to respond favorably to adjuvant immunotherapy. To determine the frequency of genomic alterations and PD-L1 status in early-stage NSCLC, we retrospectively analyzed data from 2066 unselected, single-center patients with NSCLC diagnosed using next-generation sequencing and immunohistochemistry. Nine-hundred and sixty-two patients (46.9%) presented with early-stage NSCLC. Of these, 37.0% had genomic alterations for which targeted therapies have already been approved for advanced NSCLC. The frequencies of driver mutations in the early stages were equivalent to those in advanced stages, i.e., the rates of EGFR mutations in adenocarcinomas were 12.7% (72/567) and 12.0% (78/650) in early and advanced NSCLC, respectively (p = 0778). In addition, 46.3% of early-stage NSCLC cases were PD-L1-positive, with a tumor proportion score (TPS) of ≥1%. With comparable frequencies of driver mutations in early and advanced NSCLC and PD-L1 overexpression in nearly half of patients with early-stage NSCLC, a broad spectrum of biomarkers for adjuvant and neoadjuvant therapies is available, and several are currently being investigated in clinical trials.

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“…In this study, researchers found that treatment responses in very rare EGFR mutations were highly heterogeneous. It is worth noting that there was no significant tendency for co-occurring TP53 mutations to adversely affect the outcome in EGFR -TKI-treated patients in the exon 20 insertion mutations group or the in very rare EGFR mutations group [ 32 ].…”

Section: Molecular Targetsmentioning

confidence: 99%

Biomarker-Targeted Therapies in Non–Small Cell Lung Cancer: Current Status and Perspectives

Guo

Zhang

Qin

et al. 2022

Cells

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Non-small-cell lung cancer (NSCLC) is one of the most common malignancies and the leading causes of cancer-related death worldwide. Despite many therapeutic advances in the past decade, NSCLC remains an incurable disease for the majority of patients. Molecular targeted therapies and immunotherapies have significantly improved the prognosis of NSCLC. However, the vast majority of advanced NSCLC develop resistance to current therapies and eventually progress. In this review, we discuss current and potential therapies for NSCLC, focusing on targeted therapies and immunotherapies. We highlight the future role of metabolic therapies and combination therapies in NSCLC.

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Treatment outcome of atypical EGFR mutations in the German National Network Genomic Medicine Lung Cancer (nNGM)

Cited by 58 publications

References 32 publications

Impact of smoking status on the relative efficacy of the EGFR TKI/angiogenesis inhibitor combination therapy in advanced NSCLC—a systematic review and meta-analysis

Impact of smoking status on the relative efficacy of the EGFR TKI/angiogenesis inhibitor combination therapy in advanced NSCLC—a systematic review and meta-analysis

Landscape of Genomic Alterations and PD-L1 Expression in Early-Stage Non-Small-Cell Lung Cancer (NSCLC)—A Single Center, Retrospective Observational Study

Biomarker-Targeted Therapies in Non–Small Cell Lung Cancer: Current Status and Perspectives

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