scholarly journals Canadian Consensus Recommendations on the Management of MET-Altered NSCLC

2021 ◽  
Vol 28 (6) ◽  
pp. 4552-4576
Author(s):  
Parneet K. Cheema ◽  
Shantanu O. Banerji ◽  
Normand Blais ◽  
Quincy S.-C. Chu ◽  
Patrice Desmeules ◽  
...  
Keyword(s):  
Targeted Therapies ◽  
De Novo ◽  
Growth Factor Receptor ◽  
Molecular Testing ◽  
Routine Practice ◽  
First Line ◽  
Consensus Recommendations ◽  
Met Amplification ◽  
Therapeutic Decision Making ◽  
Nsclc Patients

In Canada, the therapeutic management of patients with advanced non-small cell lung cancer (NSCLC) with rare actionable mutations differs between provinces, territories, and individual centres based on access to molecular testing and funded treatments. These variations, together with the emergence of several novel mesenchymal-epithelial transition (MET) factor-targeted therapies for the treatment of NSCLC, warrant the development of evidence-based consensus recommendations for the use of these agents. A Canadian expert panel was convened to define key clinical questions, review evidence, discuss practice recommendations and reach consensus on the treatment of advanced MET-altered NSCLC. Questions addressed by the panel include: 1. How should the patients most likely to benefit from MET-targeted therapies be identified? 2. What are the preferred first-line and subsequent therapies for patients with MET exon 14 skipping mutations? 3. What are the preferred first-line and subsequent therapies for advanced NSCLC patients with de novo MET amplification? 4. What is the preferred therapy for patients with advanced epidermal growth factor receptor (EGFR)-mutated NSCLC with acquired MET amplification progressing on EGFR inhibitors? 5. What are the potential strategies for overcoming resistance to MET inhibitors? Answers to these questions, along with the consensus recommendations herein, will help streamline the management of MET-altered NSCLC in routine practice, assist clinicians in therapeutic decision-making, and help ensure optimal outcomes for NSCLC patients with MET alterations.

Matching insurance claims data with EMR molecular status data in non-small cell lung cancer (NSCLC) patients: Understanding real-world molecular testing and prevalence rates at the site and investigator level.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20568-e20568
Author(s):  
Michael Gregory Cushion ◽  
Bhavani Krishnan ◽  
Jeff Paul Hodge ◽  
Jaya Chandra Balusu ◽  
Joseph Wagner ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Trials ◽  
Targeted Therapy ◽  
Real World ◽  
Targeted Therapies ◽  
Claims Data ◽  
Molecular Testing ◽  
Insurance Claims ◽  
Insurance Claims Data ◽  
Nsclc Patients

e20568 Background: Many targeted therapy clinical trials require a somatic gene mutation/alteration for eligibility. We assessed the feasibility of leveraging Real-World Data (RWD) to enrol NSCLC patients into clinical trials. Methods: US insurance claims data were extracted to identify lung cancer patients. These data were matched with EMR data also containing NSCLC patients’ details regarding the occurrence and results of molecular testing for EGFR, ALK, ROS1, JAK2, HER2 and RET somatic alterations, achieving a level of granular detail beyond that available in each individual dataset. A one-year extraction period was applied, with no gender or age restrictions. Results: Results for the matched dataset are summarised in the table below - the overall patient record match was 89.6%. Conclusions: The observed prevalence correlated reasonably well with literature reported prevalence for the molecular biomarkers associated commercially available targeted therapies in NSCLC (EGFR, ALK, ROS1). The sample size for the remaining biomarkers was too small to draw conclusions, though the presence of data correlating to these is of interest, considering that there are no currently approved targeted therapies in NSCLC tailored to these predictive biomarkers. This approach could be expanded upon to recruit patients into targeted therapy clinical trials as the dataset is fully linkable to sites and investigators. With the emergence of broad genomic profiling, the availability of molecular data to support clinical trial enrolment is also expected to grow.[Table: see text]

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.

scholarly journals 172P: Antacid and de novo brain metastases in EGFR-mutant NSCLC patients treated with first-line, first-generation EGFR-TKIs

2016 ◽  
Vol 11 (4) ◽  
pp. S132
Author(s):  
Y.-M. Chen ◽  
M.-C. Lin ◽  
C.-H. Lai ◽  
W.-F. Fang ◽  
H.-C. Chang ◽  
...  
Keyword(s):  
Brain Metastases ◽  
First Generation ◽  
De Novo ◽  
First Line ◽  
Egfr Mutant ◽  
Nsclc Patients ◽  
Egfr Tkis

scholarly journals Tumour tissue sampling for lung cancer management in the era of personalised therapy: what is good enough for molecular testing?

2014 ◽  
Vol 44 (4) ◽  
pp. 1011-1022 ◽  
Author(s):  
Lucia Kim ◽  
Ming Sound Tsao
Keyword(s):  
Lung Cancer ◽  
Kinase Inhibitors ◽  
Tumour Progression ◽  
Growth Factor Receptor ◽  
Nonsmall Cell Lung Cancer ◽  
Tumour Tissue ◽  
Molecular Testing ◽  
Anaplastic Lymphoma ◽  
Cancer Management ◽  
Nsclc Patients

In the era of personalised cancer therapy, the demand for molecular profiling of the patient’s tumour is steadily increasing. In advanced nonsmall cell lung cancer (NSCLC) patients, testing for epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) gene rearrangements has become an essential component of clinical practice to select patients who are most likely to benefit from EGFR and ALK tyrosine kinase inhibitors, respectively. Furthermore, obtaining tissue specimens from recurrent or metastatic tumours or from patients who develop resistance to initial effective therapies are essential for our understanding of the molecular basis of tumour progression and development of drug resistance. Therefore, the sampling of tumour tissue that is representative and is adequate in quantity and quality for pathological diagnosis and genomic profiling is crucial. In this review, we will discuss factors that should be considered in obtaining and processing biopsy specimens to enable routine molecular analysis in NSCLC patients.

scholarly journals The Exploratory Research of NSCLC with Concomitant EGFR Mutations and ALK Rearrangements

2020 ◽  
Author(s):  
Qiman Han ◽  
Chuantao Zhang ◽  
Man Jiang ◽  
Tianjun Li ◽  
Jingjuan Zhu ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Targeted Therapies ◽  
Egfr Mutations ◽  
Survival Curves ◽  
First Line ◽  
Term Survival ◽  
Anaplastic Lymphoma ◽  
Significant Difference ◽  
Nsclc Patients ◽  
Egfr Tki

Abstract Background: Epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements are two driver alterations and are generally considered mutually exclusive in non-small cell lung cancer (NSCLC). The prevalence of EGFR/ALK co-alterations in patients with NSCLC is low, and the clinicopathological features and optimal targeted therapies of these subtype of patients are still controversial. Methods: We describe three cases of NSCLC harboring EGFR mutation and ALK rearrangement. All of them received more-line therapies and showed the long-term survival benefit from targeted therapies.In addition, we searched PUBMED, EMBASE and MEDLINE up to September, 2020. 91 EGFR/ALK co-altered patients of NSCLC included for analysis in our study. Survival curves were created by Kaplan-Meier method and group comparison analyses of progression free survival (PFS) were using log-rank test. Result: A total of 91 patients were summarized in our study from previous literatures. The patients of NSCLC with coexisting EGFR mutations and ALK rearrangements are more likely to occur in female, non-smoker, Asian origin, adenocarcinoma, and IV stage. The disease control rate (DCR) of tyrosine kinase inhibitors (TKIs) which targeted EGFR and ALK as first-line targeted therapy was 62% and 78%, respectively. The median PFS on first EGFR-TKI and first ALK-TKI therapy were 5.3 months (95% confidence interval [CI] 1.20 – 9.40 months) and 6.0 months (95% CI 0.00 – 14.69 months) in EGFR/ALK co-altered NSCLC patients. Among patients who were treated with EGFR-TKI as first-line targeted therapy, univariant analysis showed that PFS have no significant difference between male and female (p = 0.22), and there is also no difference between Asian and Caucasian (p =0.939). The median PFS between first- and second-line targeted therapies was 7.0 months (95% CI 4.83 -9.17 months) and 2.0 months (95% CI 0.96-3.05 months) (p = 0.075). Survival curves showed the significantly prolonged PFS between patients without and with CNS metastasis (p = 0.036). Conclusion: Both EGFR-TKIs and ALK-TKIs have been proved their effectiveness to EGFR/ALK double-positive NSCLC patients. The curative effect of combination targeted therapies and sequential treatment regimens are still in exploration.

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