scholarly journals BRAF Mutations and Resistance of Non-Small Cell Lung Cancer to BRAF-Targeted Therapies Using Liquid Biopsy

2021 ◽  
Vol 8 (2) ◽  
pp. 110
Author(s):  
Xiaoying Zhang ◽  
Ming Li
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Targeted Therapies ◽  
Liquid Biopsy ◽  
Small Cell ◽  
Small Cell Lung ◽  
Braf Mutations

scholarly journals The Role of Pharmacists in Optimizing Molecular Testing with Evolving Biomarkers and Treatment for Non-Small Cell Lung Cancer

2021 ◽  
pp. 2240-2256
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Targeted Therapies ◽  
Small Cell ◽  
Molecular Testing ◽  
Small Cell Lung ◽  
Braf Mutations ◽  
Emerging Therapies ◽  
Oncology Care

Molecular testing and the development of targeted therapies have revolutionized the treatment of non-small cell lung cancer (NSCLC). Despite the advantages of molecular testing in patients with NSCLC and guideline recommendations, there is no specific standard testing method, resulting in variable testing practices based on institution protocol and access. Pharmacists can help to improve coordination of care around appropriate testing as results are important in determining the most appropriate targeted treatment course. The majority of patients with NSCLC are tested for PD-L1, EGFR, ALK, ROS1, and BRAF mutations. These biomarkers and their corresponding targeted therapies are more understood than the remaining biomarkers, such as KRAS, RET, MET exon 14 (METex14), and NTRK. Multiple new and emerging therapies target these latter biomarkers, and this article will focus on these lesser-known biomarkers. As the treatment of NSCLC becomes increasingly biomarker-driven and more therapies are added to the armamentarium for the management of NSCLC, pharmacists will be called upon to assist the oncology care team to optimize NSCLC treatment to improve patient outcomes.

Liquid biopsy for BRAF mutations testing in non-small cell lung cancer: a retrospective study

2020 ◽  
pp. jclinpath-2020-207107
Author(s):  
Antonino Iaccarino ◽  
Pasquale Pisapia ◽  
Francesco Pepe ◽  
Roberta Sgariglia ◽  
Mariantonia Nacchio ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Liquid Biopsy ◽  
Small Cell ◽  
Small Cell Lung ◽  
Liquid Biopsies ◽  
Braf Mutations ◽  
Advanced Stages ◽  
Nsclc Patients

V-Raf murine sarcoma viral oncogene homolog B (BRAF) gene mutations have recently been approved to select advanced stages non-small cell lung cancer (NSCLC) patients for tyrosine kinase inhibitors treatments. In this setting, liquid biopsy may represent a valuable option for BRAF mutational testing in patients without tissue availability. Here, we reviewed 196 plasma based liquid biopsies analysed by an in-house developed next generation sequencing panel, termed SiRe. On the overall, 6 (3.1%) out of 196 BRAF mutated cases were identified, with an overall median allelic frequency of 3.4%. Exon 15 p.V600E was the most common detected mutation (2/6, 33.3%). Our data highlighted that the SiRe panel is a robust tool for BRAF mutation assessment on circulating tumour DNA. Further investigation is required to develop a diagnostic algorithm to harmonise BRAF testing on tissue and blood in advanced stages NSCLC patients.

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

2021 ◽  
Vol 2 (3) ◽  
pp. 255-273
Author(s):  
Umberto Malapelle ◽  
Marcello Tiseo ◽  
Ana Vivancos ◽  
Joshua Kapp ◽  
M. Josè Serrano ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Molecular Diagnosis ◽  
Cell Lung Cancer ◽  
Targeted Therapies ◽  
Liquid Biopsy ◽  
Small Cell ◽  
Small Cell Lung ◽  
Tissue Biopsy ◽  
Biomarker Testing

The development of targeted therapies has improved survival rates for patients with advanced non-small cell lung cancer (NSCLC). However, tissue biopsy is unfeasible or inadequate in many patients, limiting biomarker testing and access to targeted therapies. The increasing numbers of established and emerging biomarkers with available targeted treatments highlights the challenges associated with sequential single-gene testing and limited tissue availability. Multiplex next-generation sequencing (NGS) offers an attractive alternative and represents a logical next step, and in cases where the tumour is inaccessible, tissue biopsy yields insufficient tumour content, or when the patient’s performance status does not allow a tissue biopsy, liquid biopsy can provide valuable material for molecular diagnosis. Here, we explore the role of liquid biopsy (i.e., circulating cell-free DNA analysis) in Europe. Liquid biopsies could be used as a complementary approach to increase rates of molecular diagnosis, with the ultimate aim of improving patient access to appropriate targeted therapies. Expert opinion is also provided on potential future applications of liquid biopsy in NSCLC, including for cancer prevention, detection of early stage and minimum residual disease, monitoring of response to therapy, selection of patients for immunotherapy, and monitoring of tumour evolution to enable optimal adaptation/combination of drug therapies.

Liquid biopsy: Safety and efficacy in a tool for molecular profiling of advanced non-small cell lung cancer (NSCLC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21506-e21506
Author(s):  
Saleha Rizwan ◽  
Zachary Otaibi ◽  
Herman Lo ◽  
Talal Khan ◽  
Rodney E. Wegner ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Targeted Therapies ◽  
Liquid Biopsy ◽  
Small Cell ◽  
Molecular Testing ◽  
Small Cell Lung ◽  
Liquid Biopsies ◽  
Nsclc Patients

e21506 Background: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer with a broad spectrum of targeted therapies already available or in clinical trials. Among the NSCLC patients, 23% to 25% harbor a mutation in a gene associated with approved or emerging targeted therapy. These therapies have changed the therapeutic landscape of NSCLC with significantly improved clinical outcomes in advanced metastatic NSCLC patients. It is imperative to test for these gene alterations in order to identify patients who could potentially benefit from these efficacious targeted therapies and to avoid therapies unlikely to provide clinical benefit. A major limitation in obtaining molecular testing occurs when minimally invasive techniques are used to obtain tissue sample resulting in insufficient yield for testing. In such cases, the utilization of circulating tumor DNA (ctDNA), commonly known as liquid biopsy, has proven very beneficial. In a study utilizing ctDNA, increased detection rates were found when using ctDNA in addition to tissue testing and a > 98.2% concordance rate was found. We report results of 40 NSCLC patients from our institute who had liquid biopsy with or without tissue profiling done. Methods: We molecularly profiled 40 newly diagnosed advanced NSCLC patients using both tissue and liquid biopsies. Tissue was assayed using the John Hopkins university molecular panel and liquid biopsies were performed by Biocept. Results: 14 out of 40 (35%) patients had insufficient or no tissue for molecular testing. Concordant results were found in 17 out of the 26 (65.4%) patients who had both tissue and liquid molecular testing done. Liquid Biopsy detected additional mutations in 5 (19.2%) patients which were not picked up on tissue and led to change in management in 4 patients. 12 out of 40 (30%) patients had repeat liquid biopsies done at progression of disease with new mutations detected on 4 patients revealing resistance to current treatment and change in treatment. Conclusions: Liquid Biopsy reveals high concordance rates with tissue genotyping and increases rate of detection of targetable mutations in NSCLC. It offers a safe and effective alternative when additional tissue is needed to identify genetic mutations.

scholarly journals Liquid Biopsy for Small Cell Lung Cancer either De Novo or Transformed: Systematic Review of Different Applications and Meta-Analysis

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2265
Author(s):  
Elio Gregory Pizzutilo ◽  
Martino Pedrani ◽  
Alessio Amatu ◽  
Lorenzo Ruggieri ◽  
Calogero Lauricella ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Systematic Review ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Liquid Biopsy ◽  
De Novo ◽  
Meta Analysis ◽  
Small Cell ◽  
Genomic Profiling ◽  
Small Cell Lung

Background: The potential added value of liquid biopsy (LB) is not well determined in the case of small cell lung cancer (SCLC), an aggressive tumor that can occur either de novo or from the histologic transformation of non-small cell lung cancer (NSCLC). Methods: A systematic review of studies adopting LB in patients with SCLC have been performed to assess the clinical utility of circulating tumor DNA (ctDNA) or circulating tumor cells (CTCs). Results: After a screening of 728 records, 62 studies (32 evaluating CTCs, 27 ctDNA, and 3 both) met predetermined eligibility criteria. Only four studies evaluated LB in the diagnostic setting for SCLC, while its prognostic significance was evaluated in 38 studies and prominently supported by both ctDNA and CTCs. A meta-analysis of 11 studies as for CTCs enumeration showed an HR for overall survival of 2.63 (1.71–4.05), with a potential publication bias. The feasibility of tumor genomic profiling and the predictive role of LB in terms of response/resistance to chemotherapy was assessed in 11 and 24 studies, respectively, with greater consistency for those regarding ctDNA. Intriguingly, several case reports suggest that LB can indirectly capture the transition to SCLC in NSCLC treated with EGFR tyrosine kinase inhibitors. Conclusions: While dedicated trials are needed, LB holds potential clinical roles in both de novo and transformed SCLC. CtDNA analysis appears the most valuable and practicable tool for both disease monitoring and genomic profiling.

Use of Liquid Biopsy in the Care of Patients with Non-Small Cell Lung Cancer

2021 ◽  
Vol 22 (10) ◽  
Author(s):  
Atocha Romero ◽  
Roberto Serna-Blasco ◽  
Virginia Calvo ◽  
Mariano Provencio
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Liquid Biopsy ◽  
Small Cell ◽  
Small Cell Lung

scholarly journals Current Status and Future Perspectives of Liquid Biopsy in Small Cell Lung Cancer

Biomedicines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 48
Author(s):  
Patricia Mondelo-Macía ◽  
Jorge García-González ◽  
Luis León-Mateos ◽  
Adrián Castillo-García ◽  
Rafael López-López ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Liquid Biopsy ◽  
Small Cell ◽  
New Drugs ◽  
Current Status ◽  
Small Cell Lung ◽  
Tumor Biopsy ◽  
Future Utility

Approximately 19% of all cancer-related deaths are due to lung cancer, which is the leading cause of mortality worldwide. Small cell lung cancer (SCLC) affects approximately 15% of patients diagnosed with lung cancer. SCLC is characterized by aggressiveness; the majority of SCLC patients present with metastatic disease, and less than 5% of patients are alive at 5 years. The gold standard of SCLC treatment is platinum and etoposide-based chemotherapy; however, its effects are short. In recent years, treatment for SCLC has changed; new drugs have been approved, and new biomarkers are needed for treatment selection. Liquid biopsy is a non-invasive, rapid, repeated and alternative tool to the traditional tumor biopsy that could allow the most personalized medicine into the management of SCLC patients. Circulating tumor cells (CTCs) and cell-free DNA (cfDNA) are the most commonly used liquid biopsy biomarkers. Some studies have reported the prognostic factors of CTCs and cfDNA in SCLC patients, independent of the stage. In this review, we summarize the recent SCLC studies of CTCs, cfDNA and other liquid biopsy biomarkers, and we discuss the future utility of liquid biopsy in the clinical management of SCLC.

scholarly journals Circulating Biomarkers of Response and Toxicity of Immunotherapy in Advanced Non-Small Cell Lung Cancer (NSCLC): A Comprehensive Review

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1794
Author(s):  
Alice Indini ◽  
Erika Rijavec ◽  
Francesco Grossi
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Liquid Biopsy ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Circulating Biomarkers ◽  
Small Cell Lung ◽  
Nsclc Patients

Immune checkpoint inhibitors (ICIs) targeting the programmed cell death (PD)-1 protein and its ligand, PD-L1, and cytotoxic T-lymphocyte-associated antigen (CTLA)-4, have revolutionized the management of patients with advanced non-small cell lung cancer (NSCLC). Unfortunately, only a small portion of NSCLC patients respond to these agents. Furthermore, although immunotherapy is usually well tolerated, some patients experience severe immune-related adverse events (irAEs). Liquid biopsy is a non-invasive diagnostic procedure involving the isolation of circulating biomarkers, such as circulating tumor cells (CTC), cell-free DNA (cfDNA), and microRNAs (miRNAs). Thanks to recent advances in technologies, such as next-generation sequencing (NGS) and digital polymerase chain reaction (dPCR), liquid biopsy has become a useful tool to provide baseline information on the tumor, and to monitor response to treatments. This review highlights the potential role of liquid biomarkers in the selection of NSCLC patients who could respond to immunotherapy, and in the identification of patients who are most likely to experience irAEs, in order to guide improvements in care.

scholarly journals SURG-05. IDEAL TREATMENT REGIMEN FOR PATIENTS WITH ≥1 BRAIN METASTASIS FROM PRIMARY NON-SMALL-CELL LUNG CANCER – A SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii204-ii204
Author(s):  
Karanbir Brar ◽  
Yosef Ellenbogen ◽  
Behnam Sadeghirad ◽  
Jiawen Deng ◽  
Winston Hou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Targeted Therapies ◽  
Meta Analysis ◽  
Performance Status ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
China National Knowledge Infrastructure

Abstract BACKGROUND Brain metastases (BM) are common in non-small cell lung cancer (NSCLC). The aim of this study was to assess the comparative effectiveness of treatments for BM from NSCLC. METHODS We searched MEDLINE, EMBASE, Web of Science, ClinicalTrials.gov, CENTRAL and references of key studies for randomized controlled trials (RCTs) published until October 2018. We also searched the Chinese databases Wanfang Data, Wanfang Med Online, China National Knowledge Infrastructure, and Chongqing VIP Information for RCTs published until September 2019. Trials including > 10 patients were selected. The primary outcomes were overall survival (OS) and intracranial progression-free survival (PFS). We used a frequentist random-effects model for network meta-analysis and assessed the certainty of evidence using the GRADE approach. RESULTS Among 8798 abstracts, 106 RCTs (9452 patients) met inclusion criteria. Median sample size was 67 (range 25-554). All trials included adult patients with histologically proven NSCLC and >1 BM proven on CT/MRI. Of trials that reported performance status (e.g. ECOG or KPS, n=67), 63/67 excluded patients with non-favorable performance status. Interventions assessed included surgery, WBRT, SRS, targeted therapies (i.e. EGFR/ALK inhibitors), and chemotherapy. Compared to WBRT alone, several interventions demonstrated a statistically significant increase in median OS, including non-targeted chemotherapy + surgery (MD: 415.3 days, 95% CI: 31.3-799.4), WBRT + EGFRi (MD: 200.2 days, 95% CI:146.3-254.1), and EGFRi alone (MD: 169.7 days, 95% CI: 49.7-289.7). Among all interventions, only WBRT + EGFRi showed a significant improvement in median PFS (MD: 108.0 days, 95%CI: 48.5-167.5). CONCLUSIONS Our preliminary analyses indicate an OS and PFS benefit on the addition of EGFR inhibitors to WBRT for the treatment of BMs from NSCLC. Further analyses of hazard ratios for OS/PFS are underway, and subgroup analyses are planned. These data support the growing role of targeted therapies in the treatment of BMs, particularly in susceptible mutant tumours.

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