scholarly journals Drug eruptions with novel targeted therapies – immune checkpoint and EGFR inhibitors

2021 ◽  
Vol 19 (11) ◽  
pp. 1621-1643
Author(s):  
Isabella Pospischil ◽  
Wolfram Hoetzenecker
Keyword(s):  
Targeted Therapies ◽  
Immune Checkpoint ◽  
Egfr Inhibitors ◽  
Drug Eruptions

scholarly journals New drug developments in metastatic gastric cancer

2018 ◽  
Vol 11 ◽  
pp. 175628481880807 ◽  
Author(s):  
Aaron C. Tan ◽  
David L. Chan ◽  
Wasek Faisal ◽  
Nick Pavlakis
Keyword(s):  
Gastric Cancer ◽  
Clinical Trials ◽  
Targeted Therapies ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Predictive Biomarkers ◽  
Metastatic Gastric Cancer ◽  
New Era

Metastatic gastric cancer is associated with a poor prognosis and novel treatment options are desperately needed. The development of targeted therapies heralded a new era for the management of metastatic gastric cancer, however results from clinical trials of numerous targeted agents have been mixed. The advent of immune checkpoint inhibitors has yielded similar promise and results from early trials are encouraging. This review provides an overview of the systemic treatment options evaluated in metastatic gastric cancer, with a focus on recent evidence from clinical trials for targeted therapies and immune checkpoint inhibitors. The failure to identify appropriate predictive biomarkers has hampered the success of many targeted therapies in gastric cancer, and a deeper understanding of specific molecular subtypes and genomic alterations may allow for more precision in the application of novel therapies. Identifying appropriate biomarkers for patient selection is essential for future clinical trials, for the most effective use of novel agents and in combination approaches to account for growing complexity of treatment options.

Therapeutic Strategies in Diseases of the Digestive Tract - 2015 and Beyond Targeted Therapies in Colon Cancer Today and Tomorrow

2016 ◽  
Vol 34 (5) ◽  
pp. 574-579 ◽  
Author(s):  
Michael Pohl ◽  
Wolff Schmiegel
Keyword(s):  
Targeted Therapies ◽  
Immune Checkpoint ◽  
Predictive Biomarkers ◽  
Therapeutic Strategies ◽  
New Drugs ◽  
Diagnostic Tools ◽  
Molecular Heterogeneity ◽  
Cancer Type ◽  
Significant Progress ◽  
Ras Genes

Background: Colorectal cancer (CRC) is the third most common cancer type in Western countries. Significant progress has been made in the last decade in the therapy of metastatic CRC (mCRC) with a median overall survival (OS) of patients exceeding 30 months. The integration of biologic targeted therapies and anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (MABs) in the treatment of patients with genomically selected all-RAS wild-type mCRC leads to a significant progress in advanced incurable disease state. After the introduction of the anti-VEGF MAB bevacizumab, the FDA approved with ramucirumab the second antiangiogenic MAB for the mCRC treatment. Further new drugs are on the horizon and new diagnostic tools will be introduced soon. Key Messages: Molecular heterogeneity of mCRC has been recognized as pivotal in the evolution of clonal populations during anti-EGFR therapies. Mutations in RAS genes predict a lack of response to anti-EGFR MABs. Mutations in the mitogen-activated protein kinase-phosphoinositide 3-kinase pathways like BRAF or PIK3CA mutations or HER2/ERBB2 or MET amplifications bypass EGFR signaling and also may confer resistance to anti-EGFR MABs. HER2/ERBB2 amplification is a further driver of resistance to anti-EGFR MABs in mCRC. The phase II study of HER2 Amplification for Colo-Rectal Cancer Enhanced Stratification (HERACLES) discovers that a dual HER2-targeted therapy may be an option for HER2-amplified mCRC. The mismatch repair deficiency predicts responsiveness to an immune checkpoint blockade with the anti-PD-1 immune checkpoint inhibitor pembrolizumab. Conclusions: The understanding of primary (de novo) and secondary (acquired) resistance to anti-EGFR therapies, new targeted therapies, immuno-oncology and about predictive biomarkers in mCRC is guiding the development of rational therapeutic strategies. Combinations of targeted therapies are necessary to effectively treat drug-resistant cancers. Liquid biopsy is an upcoming new tool in the primary diagnosis and follow-up analysis of mutations in circulating tumor DNA.

scholarly journals Indirect comparison between immune checkpoint inhibitors and targeted therapies for the treatment of melanoma

2019 ◽  
Vol 10 (24) ◽  
pp. 6114-6123
Author(s):  
Minliang Wu ◽  
Yuchong Wang ◽  
Yalong Xu ◽  
Ji Zhu ◽  
Chuan Lv ◽  
...  
Keyword(s):  
Targeted Therapies ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Indirect Comparison

scholarly journals Application of immune checkpoint inhibitors in EGFR-mutant non-small-cell lung cancer: from bed to bench

2020 ◽  
Vol 12 ◽  
pp. 175883592093033
Author(s):  
Rui Jin ◽  
Jing Zhao ◽  
Lexin Xia ◽  
Qin Li ◽  
Wen Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Targeted Therapies ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Egfr Mutant

Targeted therapies are efficient in the context of oncogenic driver mutations. Epidermal growth factor receptor (EGFR)-mutant lung cancers represent a distinct subset of non-small-cell lung cancer (NSCLC) with marked sensitivity to EGFR tyrosine kinase inhibitors (TKIs). Despite the high response rate to EGFR TKIs in EGFR-mutant lung cancer, resistance and tumor recurrence are unavoidable. Therapeutic options are restricted in patients after exhaustion of targeted therapies. Immune checkpoint inhibitors (ICIs) represent a novel therapeutic option for advanced NSCLC with significant overall survival benefit in registration trials. No superiority in terms of long-term survival was observed in the EGFR mutation subgroup when ICIs were given as monotherapy in second-line treatment in earlier studies. Thus, the appropriate application of ICIs to patients harboring EGFR mutations remains an important field of ongoing research. Here, we discuss different immune checkpoint blockade strategies, including ICIs alone and in combination with TKIs, chemotherapy, radiation, and antiangiogenic agents in EGFR-mutant NSCLC as first-line and subsequent treatments. We also summarize the evidence concerning the heterogeneous molecular features and immune signatures of EGFR mutations and their associations with ICI therapy outcomes. This study was performed to improve our understanding of the optimal mode of immune-based treatment approaches in EGFR-mutant NSCLC.

A Career in Lung Cancer: Pushing Beyond Chemotherapy

2019 ◽  
pp. 583-589
Author(s):  
Pradnya Dinkar Patil ◽  
Frances Shepherd ◽  
David H. Johnson
Keyword(s):  
Lung Cancer ◽  
Targeted Therapies ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Acquired Resistance ◽  
Genetic Alterations ◽  
Disease Biology ◽  
Formidable Challenge ◽  
Treatment Paradigm

The landscape of treatments for non–small cell lung cancer (NSCLC) has evolved dramatically over the past 3 decades. A better understanding of the disease biology and identification of actionable genetic alterations heralded an era of targeted therapies that has led to unprecedented survival benefits in patients with oncogene-driven NSCLC. More recent breakthroughs in immunotherapy led to the development of immune checkpoint inhibitors that have changed the treatment paradigm for patients with advanced NSCLC because of their ability to produce durable responses, resulting in improved survival outcomes. Despite the unparalleled success of these agents, primary and acquired resistance to these therapies pose a formidable challenge. In this article, we provide an overview of the therapeutic advances in the treatment of NSCLC, mechanisms of resistance, and potential strategies to overcome resistance to targeted therapies and immune checkpoint inhibitors.

scholarly journals Oral mucosal changes induced by anticancer targeted therapies and immune checkpoint inhibitors

2017 ◽  
Vol 25 (5) ◽  
pp. 1713-1739 ◽  
Author(s):  
Emmanuelle Vigarios ◽  
Joel B. Epstein ◽  
Vincent Sibaud
Keyword(s):  
Targeted Therapies ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Mucosal Changes

Atypical Stevens-Johnson syndrome-like reaction in the setting of immune checkpoint inhibition.

2020 ◽  
Vol 38 (5_suppl) ◽  
pp. 102-102
Author(s):  
Gabriel E. Molina ◽  
Zizi Yu ◽  
Ruth K. Foreman ◽  
Kerry Lynn Reynolds ◽  
Steven T. Chen
Keyword(s):  
Immune Checkpoint ◽  
Clinical Course ◽  
Checkpoint Inhibitors ◽  
Clinical Manifestations ◽  
Stevens Johnson Syndrome ◽  
Ocular Involvement ◽  
Drug Eruptions ◽  
Johnson Syndrome ◽  
Life Threatening ◽  
Epidermal Necrosis

102 Background: Stevens-Johnson syndrome (SJS) is a rare, life-threatening mucocutaneous toxicity that can occur in patients receiving immune checkpoint inhibitors (ICIs). ICI-induced SJS is scarcely reported in the literature and thus remains poorly understood, particularly regarding features that may distinguish it from classic SJS. Methods: To describe the timing, clinical manifestations, and treatment course of ICI-induced SJS, this multicenter, retrospective study identified seven patients with SJS in the setting of ICI use from January 2011 through May 2019. Results: All seven patients presented initially as benign, limited drug eruptions after a median of 4 ICI cycles (range, 1-7) and 63 days (range, 13-253 days) from ICI initiation. While none of the patients had prior drug allergies, all 7 were receiving new, recently initiated – i.e., within two months – medications at the time of rash onset. Cases demonstrated characteristic histologic findings of SJS, such as epidermal necrosis, and occasional unusual features, including interface dermatitis. All patients responded favorably and rapidly to systemic therapy, primarily intravenous corticosteroids, with near immediate symptomatic resolution and cessation of progressive skin blistering or detachment. Median length of stay was 11 days and no patients died from SJS. Conclusions: Our cohort defines an atypical SJS-like reaction secondary to ICI use, which is distinct from classic SJS in its delayed onset, mild initial presentation, and rare ocular involvement. The association with concomitant medication use suggests a potential mechanism whereby ICIs reduce patient immune tolerance to subsequent drug exposures. Reassuringly, this atypical SJS-like phenomenon exhibits a benign clinical course and favorable response to standard treatments.

scholarly journals Integrating immune checkpoint inhibitors and targeted therapies in the treatment of early stage non-small cell lung cancer: a narrative review

2020 ◽  
Vol 9 (6) ◽  
pp. 2656-2673
Author(s):  
Ana Ortega-Franco ◽  
Virginia Calvo ◽  
Fabio Franco ◽  
Mariano Provencio ◽  
Raffaele Califano
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Targeted Therapies ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Early Stage ◽  
Small Cell ◽  
Small Cell Lung

Data to decisions: The impact of online education on immunotherapy in advanced renal cell carcinoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17076-e17076
Author(s):  
Kinjal Parikh ◽  
Katie Lucero ◽  
Charlotte Warren ◽  
Emily Sherene Van Laar ◽  
Ann Carothers ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Online Education ◽  
Cell Carcinoma ◽  
Targeted Therapies ◽  
Immune Checkpoint ◽  
Renal Cell ◽  
Advanced Renal Cell Carcinoma ◽  
Online Video ◽  
Educational Activities ◽  
The Impact

e17076 Background: Cytokine therapy was initially the only immunotherapy for patients with advanced renal cell carcinoma (RCC). The advent of targeted therapies ushered in a new area of precision medicine in the treatment paradigm. Recently, immunotherapy in the form of immune checkpoint inhibitors has shown improved outcomes as compared to targeted therapies and has become a mainstay in treatment. As immunotherapy use moves into earlier stages of disease and combination therapies are explored, education remains essential to optimize patient outcomes. Through the partnership between Medscape Oncology and the Society for Immunotherapy of Cancer, educational activities were designed to increase the knowledge and competence among oncologists surrounding the role of immunotherapy in patients with advanced RCC and uncover remaining educational needs. Methods: The 2 educational activities included a 30-minute online, video discussion with 2 faculty presenters and synchronized slides and a text-based online activity with 2 patient cases and interactive questions. Educational effectiveness was assessed with repeated paired pre/post assessment where learners served as their own controls. The first activity launched September 19, 2018, the second activity launched December 19, 2018, and the data were collected and are reported through December 27, 2019. Results: A total of 9474 learners participated from September 2018-December 2019 including 1029 oncologists. Participation in education resulted in significant improvements for oncologist who answered all pre/post questions for an activity during the study period (n = 302). Improvements in knowledge and competency were observed in the following areas: Knowledge regarding the latest clinical trial data on the use of cancer immunotherapies for the treatment of RCC (49% vs. 74%, p < .001). Knowledge regarding the immune checkpoint inhibitor regimens on the care of patients with RCC (49% vs. 70%, p < .001). Competence related to choosing the most appropriate regimen for patients with mRCC across the continuum of care (54% vs. 76%, p < .001). Conclusions: Participation in online, video- and case-based CME-certified educational activities resulted in statistically significant gains in oncologist knowledge and competency surrounding the use of immunotherapy in advanced RCC. These results demonstrate the value and benefit of multi-modal and sequential activities on improving knowledge and competence outcomes for oncologists caring for patients with advanced renal cell carcinoma.

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