Prevalence and breakdown of EGFR exon 20 driver mutations in routine NHS lung cancer diagnostic testing

2021 ◽  
pp. jclinpath-2021-207643
Author(s):  
David Allan Moore ◽  
Kevin Jon Balbi ◽  
Benjamin Poskitt ◽  
Philip Bennett
Keyword(s):  
Lung Cancer ◽  
Diagnostic Testing ◽  
Driver Mutations ◽  
Cancer Diagnostic ◽  
Exon 20

Mutational analysis of rare insertions and deletions in exon 18 and 19 of HER2 in Chinese patients with different cancer types.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3069-3069
Author(s):  
Jianwen Qin ◽  
Dongsheng Shi ◽  
Lijie Song ◽  
Yan Yin ◽  
Bin Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Colorectal Cancer ◽  
Lung Cancer ◽  
Drug Response ◽  
Chinese Patients ◽  
Driver Mutations ◽  
Wild Type ◽  
Cancer Types ◽  
Exon 20

3069 Background: HER2 belongs to the same family with EGFR and is known as an important cancer driver gene. Kinase domain insertions and deletions (KD indels) are frequent driver mutations in both EGFR and HER2. The most common HER2 KD indels are the exon 20 insertions while others are rarely reported. Our study aimed to investigate the role of less common HER2 KD indels in solid tumors. Methods: This study was performed in 63,267 Chinese patients including 53,591 patients with lung cancer, 5,888 patients with colorectal cancer, 3,774 patients with breast cancer and 14 patients with renal pelvis cancer. Tissue or plasma samples from the patients were subjected to capture-based targeted sequencing covering HER2 and other cancer related genes. The sequencing data of each patient were retrospectively collected and analyzed. The HER2 exon 18/19 indels identified in our study were compared with data from COSMIC and MSKCC. In vitro analysis in Ba/F3 cell lines was performed to assess drug response of different HER2 exon 18/19 indels. Results: We identified recurrent HER2 KD indels in exon 18 and 19, with a frequency of 0.04% (25/63,267). The data from COSMIC and MSKCC reported the prevalence of HER2 exon 18/19 indels ranging from 0.04% to 0.23% among breast, cervical, and pancreatic cancers. In our study, HER2 exon 18/19 indels were identified in 20 patients with lung cancer (0.037%), two with colorectal cancer (0.034%), two with breast cancer (0.053%) and one with renal pelvis cancer (7.143%). Only two patients (8%) harbored concurrent actionable driver mutations including EGFR mutation and MET amplification. Meanwhile, high level of normalized allelic frequency of HER2 exon 18/19 indels was presented in most patients (22/25, 88%). In lung cancer, the presence of EGFR driver mutation was less common in patients with HER2 exon 18/19 indels than wild type HER2 (5% vs. 47.4%, p < 0.01). The rates of concurrent driver mutations in lung cancer were comparable between HER2 exon 18/19 indels and the two established HER2 drivers, exon 20 insertions and S310 mutations. The in vitro proliferation assay demonstrated that E698_P699insLL mutation in HER2 exon 18 and L755_E757delinsPQ mutation in HER2 exon 19 both conferred a survival advantage to Ba/F3 cells. Dose-response curves showed inhibitory effects on cell viability of several HER2 tyrosine kinase inhibitors including neratinib, lapatinib, poziotinib and afatinib. In particular, lapatinib, poziotinib and afatinib demonstrated comparable or stronger inhibitory ability toward the two HER2 mutants than wild type HER2 in terms of IC50. Conclusions: Our study revealed a novel class of HER2 KD indels in exon 18/19 that may act as driver mutations in several cancer types. The drug response observed in vitro indicated the potential to use anti- HER2 targeted therapies for HER2 exon 18/19 indels. Further studies on this rare type of HER2 mutation are warranted.

Impact of COVID-19 on delay in cancer diagnostic testing.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18786-e18786
Author(s):  
Anna Juncker-Jensen ◽  
Corine K. Lau ◽  
Manan Shah ◽  
Lawrence Martin Weiss ◽  
Eve Shinbrot
Keyword(s):  
Breast Cancer ◽  
Lung Cancer ◽  
Treatment Options ◽  
Diagnostic Testing ◽  
Malignant Neoplasm ◽  
Malignant Neoplasms ◽  
Test Volume ◽  
Cancer Diagnostic ◽  
The Us ◽  
Cancer Types

e18786 Background: Early diagnosis is key to the best treatment options and possible outcomes for cancer patients. However, the COVID19 pandemic has put a heavy burden on the US healthcare system, causing hospitals and medical centers to stop or delay routine cancer screenings such as mammograms, pap tests, colonoscopies, CT scans and PSA assays. Subsequently, cancer diagnostic testing and cancer patient care have also been disrupted. Methods: To determine the extent of cancer diagnostic testing that was impacted during the COVID 19 pandemic in 2020, we analyzed the changes in cancer test volume at NeoGenomics Laboratories Inc. between 2019 and 2020, and especially between March and June 2020. Unique patient test counts were categorized by cancer types as determined by the diagnostic ICD 10 code C00-D49 (with a minimum of 100 tests in 2019). Results: Comparing test volumes in 2020 to 2019, an overall decrease in tests ordered in 2020 was seen for multiple cancers. These cancers include malignant neoplasms of breast (16%) and malignant neoplasm of bronchus and lung (19%), followed by malignant neoplasm of colon, polycythemia vera, and Hodgkin lymphoma. In addition, a decrease in benign cancers, and decreases in benign neoplasm of colon, rectum, anus and anal canal was observed. To determine if the US stay-at-home order implemented between March and early June 2020 had affected test volume, month-to-month comparison shows the greatest impact in test volume in malignant neoplasm of breast: a 28% decrease comparing April 2020 to April 2019, and a 32% decrease comparing May 2020 to May 2019. Similarly, a 24% and 33% decrease were seen in malignant neoplasm of bronchus and lung for the same months. Individual tests specific for breast and lung cancer also showed similar decreases: 49-56% decrease for Breast Triple Stain (CK5 + p63 + CK 8/18), 11-41% decrease for ER test, and up to 39% decrease for HER2 diagnostic tests. Tests for ALK fusions for lung cancer showed decreases in test volume ranging from 15% to 30% during April, May and June 2020 as compared to 2019. Interestingly, we found that the total test volumes for each age group (increments of 10 up to age 80) decreased April and May 2020 as well, compared to April and May 2019. We did not see a difference in test volume decreases based on patient gender. Conclusions: There was a decrease in cancer tests ordered during the pandemic in 2020 for most cancer types, with a large decrease found in breast, lung and colon cancer. The sharp decrease in breast cancer tests is important to note as breast cancer has recently been identified as the most diagnosed form of cancer, surpassing lung cancer. This impact in cancer testing may translate to delayed diagnosis and treatment options. It remains to be seen whether this will lead to more aggressive cancer treatments, or to a greater patient mortality. It is imperative that we continue to monitor and screen patients for cancer as the pandemic continues or during any healthcare crisis in the future.

Therapeutic Approaches for the Treatment of Epidermal Growth Factor Receptor Mutated Lung Cancer

2018 ◽  
Vol 18 (8) ◽  
pp. 773-791
Author(s):  
Dhaval Sanchala ◽  
Lokesh K. Bhatt ◽  
Kedar S. Prabhavalkar
Keyword(s):  
Lung Cancer ◽  
Clinical Trial ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Driver Mutations ◽  
Therapeutic Approaches ◽  
Epidermal Growth ◽  
Egfr Mutant

Lung cancer surfaces to be the predominant determinant of mortality worldwide constituting 13% and 19% of all new cancer cases and deaths related to cancer respectively. Molecular profiling has now become a regular trend in lung cancer to identify the driver mutations. Epidermal Growth Factor Receptor (EGFR) is the most regular driver mutation encountered in Non-Small Cell Lung Cancer (NSCLC). Targeted therapies are now available for the treatment of EGFR mutant NSCLC. EGFR mutation is more frequently expressed in adenocarcinoma than squamous cell carcinoma. This article presents a detailed molecular insight of the therapeutic approaches for the treatment of EGFR mutant lung cancer. The article delineates molecular mechanism of the drugs that are approved, the drugs that are in clinical trial and the drugs that have not entered a clinical trial but shows promising future in the treatment of EGFR mutant lung cancer. Furthermore, this article provides concise information on relevant combinational or monotherapy clinical trials that have been completed for various approaches.

scholarly journals P37.23 Real-World PD-L1 Expression in Lung Cancer and its Correlation with Driver Mutations

2021 ◽  
Vol 16 (3) ◽  
pp. S452
Author(s):  
T. Wang ◽  
S. Xiao ◽  
L. Zhao ◽  
T. Chai ◽  
X. Fang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Real World ◽  
Driver Mutations

scholarly journals Molecular profile of KRAS G12C-mutant colorectal and non-small-cell lung cancer

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Luiz Henrique Araujo ◽  
Bianca Mendes Souza ◽  
Laura Rabelo Leite ◽  
Sabrina A. F. Parma ◽  
Natália P. Lopes ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Driver Mutations ◽  
Molecular Profile ◽  
Common Mutation ◽  
Small Cell Lung ◽  
The South ◽  
Nsclc Patients

Abstract Background KRAS is the most frequently mutated oncogene in cancer, however efforts to develop targeted therapies have been largely unsuccessful. Recently, two small-molecule inhibitors, AMG 510 and MRTX849, have shown promising activity in KRAS G12C-mutant solid tumors. The current study aims to assess the molecular profile of KRAS G12C in colorectal (CRC) and non-small-cell lung cancer (NSCLC) tested in a clinical certified laboratory. Methods CRC and NSCLC samples submitted for KRAS testing between 2017 and 2019 were reviewed. CRC samples were tested for KRAS and NRAS by pyrosequencing, while NSCLC samples were submitted to next generation sequencing of KRAS, NRAS, EGFR, and BRAF. Results The dataset comprised 4897 CRC and 4686 NSCLC samples. Among CRC samples, KRAS was mutated in 2354 (48.1%). Most frequent codon 12 mutations were G12D in 731 samples (14.9%) and G12V in 522 (10.7%), followed by G12C in 167 (3.4%). KRAS mutations were more frequent in females than males (p = 0.003), however this difference was exclusive of non-G12C mutants (p < 0.001). KRAS mutation frequency was lower in the South and North regions (p = 0.003), but again KRAS G12C did not differ significantly (p = 0.80). In NSCLC, KRAS mutations were found in 1004 samples (21.4%). As opposed to CRC samples, G12C was the most common mutation in KRAS, in 346 cases (7.4%). The frequency of KRAS G12C was higher in the South and Southeast regions (p = 0.012), and lower in patients younger than 50 years (p < 0.001). KRAS G12C mutations were largely mutually exclusive with other driver mutations; only 11 NSCLC (3.2%) and 1 CRC (0.6%) cases had relevant co-mutations. Conclusions KRAS G12C presents in frequencies higher than several other driver mutations, and may represent a large volume of patients in absolute numbers. KRAS testing should be considered in all CRC and NSCLC patients, independently of clinical or demographic characteristics.

scholarly journals Modelling lung cancer diagnostic pathways using discrete event simulation

2021 ◽  
pp. 1-11
Author(s):  
Tracey England ◽  
Paul Harper ◽  
Tom Crosby ◽  
Daniel Gartner ◽  
Edilson F. Arruda ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Discrete Event Simulation ◽  
Discrete Event ◽  
Event Simulation ◽  
Cancer Diagnostic ◽  
Diagnostic Pathways

Treatment in EGFR-mutated Non-small Cell Lung Cancer: How to Block the Receptor and overcome Resistance Mechanisms

2017 ◽  
Vol 103 (4) ◽  
pp. 325-337 ◽  
Author(s):  
Claudia Proto ◽  
Giuseppe Lo Russo ◽  
Giulia Corrao ◽  
Monica Ganzinelli ◽  
Francesco Facchinetti ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Growth Factor Receptor ◽  
Resistance Mechanisms ◽  
Small Cell ◽  
Third Generation ◽  
Small Cell Lung ◽  
Epidermal Growth ◽  
Exon 20 ◽  
Egfr Mutated ◽  
Egfr Tkis

In non-small cell lung cancer (NSCLC), the identification of epidermal growth factor receptor (EGFR) mutations and the parallel development of EGFR tyrosine kinase inhibitors (TKIs) have radically changed the therapeutic management strategies. Currently, erlotinib, gefitinib, and afatinib are all approved as standard first-line treatment in EGFR-mutated NSCLC. However, despite the proven efficacy, some EGFR-mutated NSCLCs do not respond to EGFR TKIs, while some patients, after a favorable and prolonged response to EGFR TKIs, inevitably progress within about 10-14 months. Epidermal growth factor receptor-dependent mechanisms, activation of alternative pathways, or phenotypic transformation can cause the resistance to EGFR TKIs. The exon 20 p.Thr790Met point mutation (T790M) is responsible for about 60% of cases of resistance when progression occurs. A third-generation TKI, osimertinib, improved outcome in patients harboring T790M after first- and second-generation TKI treatment. However, resistance develops even after treatment with third-generation drugs. To date, the Cys797Ser (C797S) mutation in exon 20 of EGFR is the most well-known resistance mutation after osimertinib. Fourth-generation TKIs are already under development. Nevertheless, additional information is needed to better understand and effectively overcome resistance. The aim of this review is to report recent advances and future perspectives in the treatment of EGFR-mutated NSCLC, highlighting the resistance mechanisms that underlie disease progression.

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