Biomarker utilization in non-small cell lung cancer, are we treating after testing?

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9609-9609
Author(s):  
Elias Makhoul ◽  
Jong Taek Kim ◽  
Wenjuan Zhang ◽  
Jean Raphael Lopategui ◽  
Ani Sarkis Balmanoukian ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Targeted Therapy ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Targeted Therapies ◽  
Small Cell ◽  
Molecular Testing ◽  
Small Cell Lung ◽  
Nsclc Patients

9609 Background: Targeted therapy in EGFR and ALK mutated non-small cell lung cancer (NSCLC) has been the standard of care for nearly a decade with subsequent FDA approvals for ROS1 and BRAF V600 mutated NSCLC occurring in 2016 and 2017. However, recent studies have shown suboptimal utilization of genomic profiling results in these patients. In 1 recent study of community oncologists, ~70% of EGFR/ALK+ patients received appropriate targeted therapy, while patients with other gene mutations (including BRAF and ROS1) only received targeted therapy ~30% of the time. Left unanswered was what patients were receiving instead and why. Additionally, it is unknown if this finding is generalizable to the academic setting. We aimed to investigate whether in our patient population, NSCLC patients with actionable mutations received associated FDA approved therapies and if not why. Methods: The pathology database was queried for all NSCLC with molecular testing (including qPCR, FISH and NGS) from 2009 to 2019. Patients with sensitizing EGFR, ALK, ROS1 or BRAF mutations that were detected after the first FDA approval for their respective targeted therapies were included for analysis with those lost to follow up subsequently excluded. Basic demographic and clinical variables were collected as well as treatment records. Results: 2160 NSCLC patients were evaluated (2160 EGFR, 1417 ALK, 810 ROS1, 589 BRAF). 468 patients were identified with targetable mutations (411 EGFR, 46 ALK, 5 ROS1, 6 BRAF). No patient had more than 1 targetable mutation. Of those patients, 248 were at an advanced stage and had clinical follow up (202 EGFR, 37 ALK, 4 ROS1, 5 BRAF). Of those patients 197/202 (97.5%), 33/37 (89.2%), 3/4 (75%) and 1/5 (20%) received EGFR, ALK, ROS1 or BRAF targeted therapy respectively. Across biomarkers 14/248 patients (5.6%) did not receive subsequent targeted therapy. 10 patients (5 EGFR, 3 ALK, 1 ROS1 and 1 BRAF) passed away before targeted therapy could be initiated. Physician choice and missed findings accounted for the remaining four cases. Conclusions: The vast majority of advanced NSCLC patients analyzed in this study received appropriate targeted therapy matched to genomic findings. The main reason (~4% of total cases) that patients did not receive therapy was due to rapidly progressive disease and death before it could be initiated. These findings are at odds with those published from the community setting. This may be due to multiple factors, including clinician education, ease of access to targeted therapies across patient populations and incomplete data in the previous study populations.

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.

Follow up analysis by exosomal miRNAs in EGFR mutated non-small cell lung cancer (NSCLC) patients during osimertinib (AZD9291) treatment: A potential prognostic biomarker tool.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. e23035-e23035 ◽  
Author(s):  
Marco Giallombardo ◽  
Jorge Jorge Chacartegui ◽  
Pablo Reclusa ◽  
Jan P. Van Meerbeeck ◽  
Riccardo Alessandro ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Prognostic Biomarker ◽  
Small Cell ◽  
Small Cell Lung ◽  
Exosomal Mirnas ◽  
Nsclc Patients ◽  
Egfr Mutated

The targetable mutation landscape of Chinese patients with non-small cell lung cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13018-e13018
Author(s):  
Jun Li ◽  
Cuiyun Zhang ◽  
Jiuzhou Zhao ◽  
Zhizhong Wang ◽  
Bing Wei ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Small Cell ◽  
Chinese Patients ◽  
Molecular Testing ◽  
Small Cell Lung ◽  
Essential Information ◽  
Nsclc Patients

e13018 Background: In recent years, the prognosis of non-small cell lung cancer (NSCLC) patients has been substantially improved by targeted therapies against specific molecular aberrations, i.e. tyrosine kinase inhibitors (TKIs) for Epidermal Growth Factor Receptor ( EGFR) etc. Several genes have been suggested by NCCN guideline (v7.2017) to test for NSCLC patients, including EGFR, ALK, ROS1, BRAF, MET, RET, HER2 and KRAS. The aim of this study is to profile the landscape of actionable mutations in Chinese NSCLC patients. Methods: From 2015 to 2017 621 treatment naïve NSCLC patients enrolled in the affiliated cancer hospital of Zhengzhou University were included in this analysis. DNA was extracted from the FFPE biopsies of these patients and processed for target capture sequencing covering the exons and flanking splicing regions of the 8 genes suggested by NCCN guideline, as well as introns of ROS, ALK and RET. Results: In total, 593 out of the 621 NSCLC patients harbor one or more mutations in these 8 genes, accounting for 95.5% of all the cases. EGFR, ALK and HER2 are the top 3 mutants, with a frequency of 52%, 32% and 26% respectively. Genetic aberrations in BRAF, MET, ROS1, KRAS and RET occur in 22%, 18%, 16% and 14% of the patients. The most common variation is missense; T > G, C > T and C > A changes are more often observed than T > C, T > A and C > G; the median number of variants per sample is 2, ranging from 1 to 13. There are 418 mutations detected on EGFR, of which 206 (49.28%) are clinically relevant. EGFR L858R, Exon19 deletion, Exon20 insertion, G719, A750P were observed in 123 (29.43%), 43 (10.29%), 8 (1.91%), 6 (1.44%) and 6 (1.44%) cases respectively. Gene fusions were identified in 78 cases, and the EML4- ALK is the most common one occurred in 54 patients, other fusion genes include KIF5B- ALK (11) ， CCDC6- RET (4), CD74- ROS1 (4), EZR- ROS1 (2), ERC1- RET (1), , SDC4- ROS1 (1) and TCOF1- ROS1 (1). Conclusions: Target sequencing of the 8 genes suggested by NCCN guideline for NSCLC patients reveals essential information for designing personalized therapeutic regimen. Chinese patients, maybe other Asian countries also, may benefit more from this molecular testing, because of the high occurrence of actionable 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.

scholarly journals Association of immune-related pneumonitis with the efficacy of PD-1/PD-L1 inhibitors in non-small cell lung cancer

2020 ◽  
Vol 12 ◽  
pp. 175883592092203
Author(s):  
Pengfei Cui ◽  
Di Huang ◽  
Zhaozhen Wu ◽  
Haitao Tao ◽  
Sujie Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Checkpoint Inhibitor ◽  
Small Cell ◽  
Rank Test ◽  
Small Cell Lung ◽  
Cryptogenic Organizing Pneumonia ◽  
Nsclc Patients

Background: Cutaneous adverse events (AEs) have been positively associated with immune checkpoint inhibitor (ICI) efficacy in patients with melanoma, but little is known regarding the association between checkpoint inhibitor pneumonitis (CIP) and programmed cell death protein 1/programmed death ligand 1 (PD-1/PD-L1) inhibitor efficacy in non-small cell lung cancer (NSCLC). Methods: A single-institution, retrospective medical record review of patients with advanced or recurrent NSCLC who were treated with PD-1/PD-L1 inhibitors between 1 September 2015 and 1 June 2019 was conducted. A total of 276 NSCLC patients with or without immune-related pneumonitis who received at least one dose of ICIs and had at least one follow-up visit were identified. Kaplan–Meier curves of the progression-free survival (PFS) of patients stratified according to immune-related pneumonitis development were evaluated with the log-rank test as a preplanned primary objective. Multivariate analysis of PFS was performed with Cox proportional hazard regression models. Results: In the cohort of 276 patients, 42 patients developed CIP attributed to PD-1/PD-L1 inhibitors. Survival analysis showed that the overall response rate was significantly higher in patients with CIP than in those without CIP (61.90% versus 29.91%, respectively, p < 0.01), and that CIP development was significantly associated with increased PFS (45.80 weeks versus 21.15 weeks, respectively, p < 0.01). Additionally, 16-week landmark analysis produced the same results. Similarly, subgroup analysis of PD-1 inhibitor-treated, nivolumab-treated, and pembrolizumab-treated groups also revealed that CIP increased survival in NSCLC patients. Additionally, grade 1–2 pneumonitis showed an association with increased ICI efficacy in NSCLC; however, grade 3–4 pneumonitis did not. In addition, only two of the four pneumonitis radiological subtypes showed associations with increased ICI efficacy in NSCLC. Conclusion: CIP is associated with enhanced PD-1/PD-L1 inhibitor efficacy in NSCLC patients. Grade 1–2 pneumonitis and the radiological features of hypersensitivity and cryptogenic organizing pneumonia (COP) may be signs of enhanced ICI efficacy. However, further studies with larger numbers of patients and longer follow-up times are needed to validate our findings.

scholarly journals Evaluation of the Lung Immune Prognostic Index in Non-Small Cell Lung Cancer Patients Treated With Systemic Therapy: A Retrospective Study and Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Litang Huang ◽  
Hedong Han ◽  
Li Zhou ◽  
Xi Chen ◽  
Qiuli Xu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Targeted Therapy ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Systemic Therapy ◽  
Meta Analysis ◽  
Prognostic Index ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

The lung immune prognostic index (LIPI) has been shown to be an important prognostic marker for various tumors. However, the prognostic value of LIPI among non-small cell lung cancer (NSCLC) patients treated with systemic therapy remains controversial. We aimed to evaluate survival status according to LIPI among NSCLC patients receiving different forms of systemic therapy at our institution. We also performed a meta-analysis of articles from PubMed and Embase to illustrate this question. For our cohort, we found that good LIPI was associated with better overall survival (OS) among 91 patients on immunotherapy, 329 patients on targeted therapy, and 570 patients on chemotherapy. For the meta-analysis, a total of eight studies with 8,721 patients were included. Pooled results showed that a higher LIPI (those with 1 or 2 factors) was associated with poor overall progression-free survival (PFS) (hazard ratio [HR], 1.57; 95% confidence interval [CI], 1.45−1.71) and OS (HR, 2.01; 95% CI, 1.75−2.31). Subgroup analyses showed that a higher LIPI was related to poor survival among patients prescribed different systemic therapies: immunotherapy (OS HR, 2.50; 95% CI, 1.99–3.13; PFS HR, 1.77; 95% CI, 1.56–2.01), chemotherapy (OS HR, 1.58; 95% CI, 1.34–1.86; PFS HR, 1.38; 95% CI, 1.23–1.55), and targeted therapy (OS HR; 2.15, 95% CI, 1.57–2.96; PFS HR, 1.60; 95% CI, 1.25–2.06). The study shows that the LIPI is a clinically significant prognostic factor for NSCLC patients receiving systemic therapy.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD420209009.

scholarly journals TARGETED THERAPY OF NON-SMALL-CELL LUNG CANCER PATIENTS: MOST COMMON ADVERSE EVENTS AND METHODS OF THEIR CORRECTIONS

2017 ◽  
Vol 22 (6) ◽  
pp. 300-306
Author(s):  
Elena V. Reutova ◽  
K. P Laktionov ◽  
M. S Ardzinba
Keyword(s):  
Lung Cancer ◽  
Targeted Therapy ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Serious Adverse Events ◽  
Long Term Treatment ◽  
Nsclc Patients

Major advances in the treatment of non-small-cell lung cancer (NSCLC) patients are associated with the targeted therapy. It is both highly effective in the presence of activating mutations in the tumor and generally well-tolerated. Serious adverse events are recorded much less than with chemotherapy. There are significant differences in the toxicity profile. Both early detection and proper and timely correction of complications of targeted therapies are necessary for the successful long-term treatment of metastatic NSCLC patients.

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