HSR19-099: Harnessing the Voice of Patients With Genetic Mutations in NSCLC Treatment

2019 ◽  
Vol 17 (3.5) ◽  
pp. HSR19-099
Author(s):  
Suepattra G. May ◽  
Caroline Huber ◽  
Alison R. Silverstein ◽  
Mark Linthicum ◽  
Jason Shafrin ◽  
...  
Keyword(s):  
Treatment Options ◽  
Specific Treatment ◽  
Genetic Mutation ◽  
Patient Treatment ◽  
Driver Mutations ◽  
Genetic Mutations ◽  
Mutation Status ◽  
Metastatic Nsclc ◽  
Patient Goals ◽  
Nsclc Patients

Background: Targeted therapies for non-small lung cancer (NSCLC) have vastly improved survival and other outcomes for patients whose tumors have genetic mutations such as ALK, BRAF, EGFR, and ROS1. Identification of genetic mutations often indicates a mutation-specific course of therapy; however, the relationship between genetic mutation status, patient treatment preferences, and other determinants of patient value in NSCLC cancer care is not well understood. Methods: Qualitative study utilizing focus groups and in-depth interviews were conducted with metastatic NSCLC patients who had received systemic therapy. Interviews explored how patients valued and prioritized factors and attributes associated with NSCLC therapy. Interviews were audio-recorded, transcribed, and coded for key themes using MAXQDA qualitative data analysis software (VERBI, GmbH). Thematic analysis identified determinants of value that patients with genetic mutations considered most important in decision-making. Results: Of 19 total participants with metastatic NSCLC (mean [SD] age, 55.8 [12.6] years; 79% female), 15 (79%) reported a known genetic mutation. Most participants valued oncogene testing and indicated that they had developed a distinct identity based on their specific mutation. Further, participants in our study with identified mutations reported facing distinctly different decisions than those without known mutations. Participants also highlighted unmet needs for diagnosis, treatment, and support tailored to their patient subgroup, including a critical need for better provider training and awareness of genetic testing and mutation-specific treatment options. Across patient subgroups, mutation-specific social media and support networks were highly valued for the care and treatment information they provide, especially among those with rare mutations, limited treatment options, or less-experienced providers. Conclusions: Our study suggests important differences among NSCLC patients based on identified genetic mutations. As treatment for NSCLC evolves, so do the needs and preferences of patients, especially those with driver mutations. Our findings highlight the need for a better understanding of how mutation status may impact patient goals and preferences in order to provide the highest value care to each patient.

Afatinib monotherapy in patients with metastatic squamous cell carcinoma of the lung progressing after erlotinib/gefitinib (E/G) and chemotherapy: Interim subset analysis from a phase III trial.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7558-7558 ◽  
Author(s):  
Joo-Hang Kim ◽  
Francesco Grossi ◽  
Filippo De Marinis ◽  
Manuel Cobo ◽  
James Chih-Hsin Yang ◽  
...  
Keyword(s):  
Tyrosine Kinases ◽  
Treatment Options ◽  
Phase Iii ◽  
Open Label ◽  
Metastatic Nsclc ◽  
Erbb4 Receptor ◽  
Grade 3 ◽  
Patient Enrolment ◽  
Nsclc Patients ◽  
To Receive

7558 Background: Patients with squamous NSCLC have limited treatment options. For those deriving benefit from EGFR TKIs, it is unclear whether sustained ErbB family blockade offers benefit upon progression. We evaluated afatinib, an irreversible blocker of EGFR (ErbB1), HER2 (ErbB2) and ErbB4 receptor tyrosine kinases, in patients with metastatic NSCLC who had failed chemotherapy and E/G. Here we describe a pre-specified analysis of those with squamous histology in Part A. Methods: This randomized Phase III, open-label, multi-center trial enrolled patients with pathologically confirmed metastatic NSCLC after failing ≥1 line of cytotoxic chemotherapy and E/G. In Part A, patients received oral afatinib 50 mg until disease progression. Those with clinical benefit (≥12 wks) who progressed were eligible to receive afatinib plus paclitaxel or investigator’s choice chemotherapy (Part B). Primary endpoint was PFS (RECIST 1.1). Following an amendment, an interim analysis of Part A was performed to assess afatinib monotherapy. Results: Patient enrolment into Part A was from April 2010 to May 2011. Of 1154 afatinib-treated patients, 91 (8%) had squamous histology; 18/91 and 40/91 had CR/PR and SD on prior E/G, respectively (by investigator). Median age was 63 yrs, 71% were male, 76% were current/ex-smokers. Median PFS on afatinib was 3.7 mths in the squamous histology subset. Of 91 patients, 42 had PFS ≥3 mths; 13 had PFS of ≥6 mths. In evaluable patients (n=77), 1 CR and 3 PRs were confirmed; 51 and 22 patients had best overall response of SD and PD, respectively. Of the 31 patients with PD on prior E/G with no intervening chemotherapy, 10 achieved confirmed disease control (2 PR; 8 SD) on afatinib. Most commonly reported grade 3/4 adverse events (AEs) in Part A were diarrhea (13%) and rash/acne (12%). The safety profile in the squamous histology subset was similar to that observed for the whole trial. Conclusions: Afatinib monotherapy demonstrated encouraging activity in treatment-refractory NSCLC patients with squamous histology that merits further evaluation.

scholarly journals Does the Waiting Period for Genetic Tests Affect the Prognosis in Chemotherapy-Treated de novo Metastatic Non-Small Cell Lung Cancer Patients without a Driver Mutation?

2020 ◽  
pp. 1-7
Author(s):  
Serdar Arici ◽  
Abdullah Sakin ◽  
Ruhper Cekin ◽  
Saban Secmeler ◽  
Nurgül Yasar ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
De Novo ◽  
Small Cell ◽  
Driver Mutations ◽  
Small Cell Lung ◽  
Metastatic Nsclc ◽  
Group A ◽  
Nsclc Patients

<b><i>Introduction:</i></b> The length of the necessary waiting period to test driver mutations may generate anxiety in patients and clinicians. For this reason, an investigation was conducted to determine whether the duration between diagnosis and the start of first-line chemotherapy (DDC) in non-small cell lung cancer (NSCLC) patients without driver mutations has an impact on prognosis. <b><i>Methods:</i></b> The study included 303 de novo metastatic NSCLC patients without a driver mutation and patients were divided into 2 groups according to DDC: ≤30 days (group A) or &#x3e;30 days (group B). The determinant factors for progression-free survival (PFS) and overall survival (OS) were examined by Cox regression analysis. <b><i>Results:</i></b> The mean DDC was calculated as 38.2 ± 54.5 days. The number of patients in group A and B were 183 and 120, respectively. The median PFS in groups A and B was 5.0 and 6.0 months (<i>p</i> = 0.268) and the median OS was 10.0 and 11 months, respectively (<i>p</i> = 0.341). Univariate and multivariate analyses revealed that DDC was not a factor associated with PFS and OS. <b><i>Conclusion:</i></b> Our results show that a higher DDC was not associated with a worse prognosis in metastatic NSCLC patients without driver mutations. In this context, it is safer for patients and their physicians to wait for test results before starting chemotherapy.

scholarly journals Molecular Subtypes and Precision Oncology in Intrahepatic Cholangiocarcinoma

2021 ◽  
Vol 10 (13) ◽  
pp. 2803
Author(s):  
Carolin Czauderna ◽  
Martha M. Kirstein ◽  
Hauke C. Tews ◽  
Arndt Vogel ◽  
Jens U. Marquardt
Keyword(s):  
Clinical Care ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Specific Treatment ◽  
Growth Factor Receptor ◽  
Treatment Modalities ◽  
Precision Oncology ◽  
Recurrence Rates ◽  
Isocitrate Dehydrogenase 1 ◽  
Liver Cancers

Cholangiocarcinomas (CCAs) are the second-most common primary liver cancers. CCAs represent a group of highly heterogeneous tumors classified based on anatomical localization into intra- (iCCA) and extrahepatic CCA (eCCA). In contrast to eCCA, the incidence of iCCA is increasing worldwide. Curative treatment strategies for all CCAs involve oncological resection followed by adjuvant chemotherapy in early stages, whereas chemotherapy is administered at advanced stages of disease. Due to late diagnosis, high recurrence rates, and limited treatment options, the prognosis of patients remains poor. Comprehensive molecular characterization has further revealed considerable heterogeneity and distinct prognostic and therapeutic traits for iCCA and eCCA, indicating that specific treatment modalities are required for different subclasses. Several druggable alterations and oncogenic drivers such as fibroblast growth factor receptor 2 gene fusions and hotspot mutations in isocitrate dehydrogenase 1 and 2 mutations have been identified. Specific inhibitors have demonstrated striking antitumor activity in affected subgroups of patients in phase II and III clinical trials. Thus, improved understanding of the molecular complexity has paved the way for precision oncological approaches. Here, we outline current advances in targeted treatments and immunotherapeutic approaches. In addition, we delineate future perspectives for different molecular subclasses that will improve the clinical care of iCCA patients.

scholarly journals FP12.06 GRIm-Score Variations Predict Outcome in Metastatic NSCLC Patients Treated with First-Line Pembrolizumab

2021 ◽  
Vol 16 (3) ◽  
pp. S219
Author(s):  
E. Lenci ◽  
L. Cantini ◽  
S. Rinaldi ◽  
F. Pecci ◽  
V. Cognigni ◽  
...  
Keyword(s):  
First Line ◽  
Metastatic Nsclc ◽  
Nsclc Patients

scholarly journals Hypoxia-inducible Factor 2α: A Key Player in Tumorigenesis and Metastasis of Pheochromocytoma and Paraganglioma?

2021 ◽  
Author(s):  
Nicole Bechmann ◽  
Graeme Eisenhofer
Keyword(s):  
Extracellular Matrix ◽  
Signaling Pathways ◽  
Metastatic Disease ◽  
Therapeutic Intervention ◽  
Treatment Options ◽  
Hypoxia Inducible Factor ◽  
Germline Mutations ◽  
Driver Mutations ◽  
Mesenchymal Transition ◽  
Therapeutic Relevance

AbstractGermline or somatic driver mutations linked to specific phenotypic features are identified in approximately 70% of all catecholamine-producing pheochromocytomas and paragangliomas (PPGLs). Mutations leading to stabilization of hypoxia-inducible factor 2α (HIF2α) and downstream pseudohypoxic signaling are associated with a higher risk of metastatic disease. Patients with metastatic PPGLs have a variable prognosis and treatment options are limited. In most patients with PPGLs, germline mutations lead to the stabilization of HIF2α. Mutations in HIF2α itself are associated with adrenal pheochromocytomas and/or extra-adrenal paragangliomas and about 30% of these patients develop metastatic disease; nevertheless, the frequency of these specific mutations is low (1.6–6.2%). Generally, mutations that lead to stabilization of HIF2α result in distinct catecholamine phenotype through blockade of glucocorticoid-mediated induction of phenylethanolamine N-methyltransferase, leading to the formation of tumors that lack epinephrine. HIF2α, among other factors, also contributes importantly to the initiation of a motile and invasive phenotype. Specifically, the expression of HIF2α supports a neuroendocrine-to-mesenchymal transition and the associated invasion-metastasis cascade, which includes the formation of pseudopodia to facilitate penetration into adjacent vasculature. The HIF2α-mediated expression of adhesion and extracellular matrix genes also promotes the establishment of PPGL cells in distant tissues. The involvement of HIF2α in tumorigenesis and in multiple steps of invasion-metastasis cascade underscores the therapeutic relevance of targeting HIF2α signaling pathways in PPGLs. However, due to emerging resistance to current HIF2α inhibitors that target HIF2α binding to specific partners, alternative HIF2α signaling pathways and downstream actions should also be considered for therapeutic intervention.

scholarly journals Liquid Biopsy Analysis in Clinical Practice: Focus on Lung Cancer

2021 ◽  
Vol 2 (3) ◽  
pp. 241-254
Author(s):  
Pasquale Pisapia ◽  
Francesco Pepe ◽  
Antonino Iaccarino ◽  
Roberta Sgariglia ◽  
Mariantonia Nacchio ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Liquid Biopsy ◽  
Treatment Options ◽  
Molecular Testing ◽  
Specific Information ◽  
Sample Collection ◽  
Timely Manner ◽  
Oncology Practice ◽  
Nsclc Patients ◽  
To Receive

Lung cancer is the leading cause of cancer death worldwide. Despite the emergence of highly effective targeted therapies, up to 30% of advanced stage non-small cell lung cancer (NSCLC) patients do not undergo tissue molecular testing because of scarce tissue availability. Liquid biopsy, on the other hand, offers these patients a valuable opportunity to receive the best treatment options in a timely manner. Indeed, besides being much faster and less invasive than conventional tissue-based analysis, it can also yield specific information about the genetic make-up and evolution of patients’ tumors. However, several issues, including lack of standardized protocols for sample collection, processing, and interpretation, still need to be addressed before liquid biopsy can be fully incorporated into routine oncology practice. Here, we reviewed the most important challenges hindering the implementation of liquid biopsy in oncology practice, as well as the great advantages of this approach for the treatment of NSCLC patients.

scholarly journals TET2 Mutation and High miR-22 Expression as Biomarkers to Predict Clinical Outcome in Myelodysplastic Syndrome Patients Treated with Hypomethylating Therapy

2021 ◽  
Vol 43 (2) ◽  
pp. 917-931
Author(s):  
Jina Yun ◽  
Young Sok Ji ◽  
Geum Ha Jang ◽  
Sung Hee Lim ◽  
Se Hyung Kim ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Odds Ratio ◽  
Lower Risk ◽  
Genetic Mutations ◽  
Dna Hypermethylation ◽  
Leukemic Transformation ◽  
Mutation Status ◽  
Similar Tendency ◽  
Tet2 Mutation ◽  
Expression Status

Tet methylcytosine dioxygenase 2 (TET2) is one of the most frequently mutated genes in myelodysplastic syndrome (MDS). TET2 is known to involve a demethylation process, and the loss of TET2 is thought to cause DNA hypermethylation. Loss of TET2 function is known to be caused by genetic mutations and miRNA, such as miR-22. We analyzed 41 MDS patients receiving hypomethylating therapy (HMT) to assess whether TET2 mutation status and miR-22 expression status were associated with their clinical characteristics and treatment outcomes. Responsiveness to HMT was not affected by both TET2 mutation (odds ratio (OR) 0.900, p = 0.909) and high miR-22 expression (OR 1.548, p = 0.631). There was a tendency for TET2 mutation to be associated with lower-risk disease based on IPSS (Gamma = −0.674, p = 0.073), lower leukemic transformation (OR 0.170, p = 0.040) and longer survival (Hazard ratio 0.354, p = 0.059). Although high miR-22 expression also showed a similar tendency, this tendency was weaker than that of TET2 mutation. In summary, the loss of TET2 function, including both TET2 mutation and high miR-22 expression, was not a good biomarker for predicting the response to HMT but may be associated with lower-risk disease based on IPSS, lower leukemic transformation and longer survival.

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.

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