Master protocols in lung cancer: experience from Lung Master Protocol

Purpose of review Contemporary advances in the understanding of the molecular and immunologic basis of metastatic lung cancer have firmly changed its treatment paradigm to a personalized, biomarker-driven approach. However, the majority of lung-cancer patients [especially lung squamous cell carcinoma (LUSC)] still do not have effective targeted therapeutic options. Master protocols, such as Lung-MAP, represent an innovative clinical trial approach designed to accelerate evaluation of novel biomarker-driven therapies. Recent findings Lung-MAP is an umbrella trial for advanced LUSC and has been active since 2014. Cumulative experience from this overarching, multi-institution master protocol has demonstrated that centralized, real-time biomarker screening is feasible and substudy modularity is essential for protocol adaptability in a rapidly changing treatment landscape. In addition, screening and efficacy results from Lung-MAP affirm that LUSC has several putative drivers but remains difficult to effectively treat with targeted therapy. Summary Master protocols are a feasible and efficient approach for evaluating biomarker-driven therapies in lung cancer. As we begin to target less common genomic and immunotherapy subtypes, centrally coordinated clinical trial designs such as Lung-MAP are necessary to rapidly deliver effective therapies to patients, whereas also maximizing the quality of research data obtained.
Source: Current Opinion in Oncology - Category: Cancer & Oncology Tags: LUNG AND MEDIASTINUM: Edited by Robert Pirker Source Type: research

Related Links:

DNA-damaging chemotherapy and radiation therapy are integrated into the treatment paradigm of the majority of cancer patients. Recently, immunotherapy that targets the immunosuppressive interaction between programmed death 1 (PD-1) and its ligand PD-L1 has been approved for malignancies including non–small cell lung cancer, melanoma, and head and neck squamous cell carcinoma. ATR is a DNA damage–signaling kinase activated at damaged replication forks, and ATR kinase inhibitors potentiate the cytotoxicity of DNA-damaging chemotherapies. We show here that the ATR kinase inhibitor AZD6738 combines with conformal r...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Authors: Rolfes V, Idel C, Pries R, Plötze-Martin K, Habermann J, Gemoll T, Bohnet S, Latz E, Ribbat-Idel J, Franklin BS, Wollenberg B Abstract Cancer immunotherapy has been revolutionised by drugs that enhance the ability of the immune system to detect and fight tumors. Immune checkpoint therapies that target the programmed death-1 receptor (PD-1), or its ligand (PD-L1) have shown unprecedented rates of durable clinical responses in patients with various cancer types. However, there is still a large fraction of patients that do not respond to checkpoint inhibitors, and the challenge remains to find cellular a...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
AbstractBackgroundThe clinical efficacy observed with inhibitors of programed cell death 1/programed cell death ligand 1 (PD-L1/PD-1) in cancer therapy has prompted studies to characterize the immune response in several tumor types, including lung cancer. However, the immunological profile of non –small cell lung carcinoma (NSCLC) treated with neoadjuvant chemotherapy (NCT) is not yet fully characterized, and it may be therapeutically important. The aim of this retrospective study was to characterize and quantify PD-L1/PD-1 expression and tumor-associated immune cells (TAICs) in surgically resected NSCLCs from patien...
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
Rationale: Novel treatment strategies such as immunotherapy are being evaluated to further improve the outcomes of colorectal cancer patients. To our knowledge, this is the first report to show both the successful treatment of pulmonary squamous cell carcinoma (SCC) with pembrolizumab alongside histological and immunohistochemical findings of resected colon cancer under immunotherapy for lung cancer. Patient concerns: This patient was a 70-year-old man who presented with a right lung tumor and simultaneous adenocarcinoma of the sigmoid colon. Diagnoses: Biopsy examination revealed squamous cell carcinoma in the rig...
Source: Medicine - Category: Internal Medicine Tags: Research Article: Clinical Case Report Source Type: research
SummaryImmunotherapies comprise of a  class of cancer therapies that are increasingly used for treatment of several cancer entities. Active immunotherapies encompassing immune checkpoint inhibitors are the most widespread class of immunotherapies, with indications for melanoma, non-small lung cancer, renal cell carcinoma, urothelial c arcinoma, head and neck squamous cell carcinoma, and Hodgkin’s lymphoma. Immune checkpoint inhibitors have demonstrated unique response patterns that are not adequately captured by traditional response criteria such das the Response Evaluation Criteria in Solid Tumors (RECIST) and ...
Source: Memo - Magazine of European Medical Oncology - Category: Cancer & Oncology Source Type: research
AbstractOver the last two decades, molecular-targeted agents have become mainstream treatment for many types of malignancies and have improved the overall survival of patients. However, most patients eventually develop resistance to these targeted therapies. Recently, immunotherapies such as immune checkpoint inhibitors have revolutionized the treatment paradigm for many types of malignancies. Immune checkpoint inhibitors have been approved for treatment of melanoma, non-small cell lung cancer, renal cell carcinoma, head and neck squamous cell carcinoma, Hodgkin ’s lymphoma, bladder cancer and gastric cancer. However...
Source: International Journal of Clinical Oncology - Category: Cancer & Oncology Source Type: research
Abstract BACKGROUND: Immune checkpoint inhibitors targeting the PD-L1 pathway have shown benefit for the treatment of metastatic non-small cell lung cancer (NSCLC). However, the prognostic value of PD-L1 independent of immunotherapy is still unclear, with conflicting results reported between PD-L1 expression and patient survival. Our aim was to correlate PD-L1 mRNA level with clinical and pathologic factors and to investigative the prognostic value of PD-L1 mRNA in all stages of NSCLC. METHODS: Gene expression and clinical data were obtained from public TCGA repositories from the National Cancer Institute. Ge...
Source: The Annals of Thoracic Surgery - Category: Cardiovascular & Thoracic Surgery Authors: Tags: Ann Thorac Surg Source Type: research
Conclusions Our results suggest that the value of PD-L1 mRNA in prognosticating outcome in lung cancer is limited. Further studies are needed to identify novel prognostic biomarkers other than PD-L1 that are associated with improved patient survival. Identification of further prognostically important biomarkers may prove useful in identifying patients suitable for immunotherapy.
Source: The Annals of Thoracic Surgery - Category: Cardiovascular & Thoracic Surgery Source Type: research
Discussion of current strategies targeting the immune system related to solid tumors with emphasis on head and neck squamous cell carcinoma (HNSCC).This review will outline the current challenges with immunotherapy and future goals for treatment using these agents.Recent FindingsAgents targeting immune checkpoint receptors (IR) such as program death 1 (PD1) have been used in the clinical realm for melanoma and non-small cell lung cancer (NSCLC), and the use of these agents for these malignancies has provided crucial information about how and why patients respond or not to inhibitory checkpoint receptor blockade therapy (IC...
Source: Current Oncology Reports - Category: Cancer & Oncology Source Type: research
Authors: Xiong D, Pan J, Yin Y, Jiang H, Szabo E, Lubet RA, Wang Y, You M Abstract Lung squamous cell carcinoma (LUSC) is a major subtype of Non-Small Cell Lung Cancer. To increase our understanding of the LUSC pathobiology, we performed exome sequencing and RNA-seq in 16 murine carcinogen-induced LUSC tumors and 8 normal murine lung tissue samples. Additionally, we conducted single-cell RNA-seq on two independent tumors from the same murine model. We identified a list of 59 cancer genes recurrently mutated in the mice LUSC tumors, 47 (80%) of which were also mutated in human LUSCs. At the single cell level, we det...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
More News: Allergy & Immunology | Cancer | Cancer & Oncology | Carcinoma | Clinical Trials | Immunotherapy | Lung Cancer | Skin Cancer | Squamous Cell Carcinoma