scholarly journals Future Perspective of Chemotherapy and Pharmacotherapy in Thymic Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5239
Author(s):  
Rui Kitadai ◽  
Yusuke Okuma
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Thymic Carcinoma ◽  
Checkpoint Inhibitors ◽  
Genetic Alterations ◽  
Cytotoxic Agents ◽  
Future Perspective ◽  
Driver Mutations ◽  
Thymic Epithelial Cells ◽  
Thymic Epithelial Tumors

Thymic carcinoma is a rare cancer that arises from thymic epithelial cells. Its nature and pathology differ from that of benign thymoma, presenting a poorer prognosis. If surgically resectable, surgery alone or surgery followed by chemoradiotherapy or radiotherapy is recommended by the National Comprehensive Cancer Network Guidelines. Metastatic and refractory thymic carcinomas require systemic pharmacotherapy. Combined carboplatin and paclitaxel, and cisplatin and anthracycline-based regimens have been shown a fair response rate and survival to provide a de facto standard of care when compared with other drugs employed as first-line chemotherapy. Cytotoxic agents have been pivotal for treating thymic carcinoma, as little is known regarding its tumorigenesis. In addition, genetic alterations, including driver mutations, which play an important role in treatments, have not yet been discovered. However, molecular pathways and biomarker studies assessing thymic epithelial tumors have been reported recently, resulting in the development of new agents, such as molecular targeted agents and immune checkpoint inhibitors. As treatment options are currently limited and the prognosis remains poor in metastases and recurrent thymic carcinoma, genetic alterations need to be assessed. In the present review, we focused on the current role of targeted therapies and immune checkpoint inhibitors in treating thymic carcinoma.

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 Immunobiology of Thymic Epithelial Tumors: Implications for Immunotherapy with Immune Checkpoint Inhibitors

2020 ◽  
Vol 21 (23) ◽  
pp. 9056
Author(s):  
Valentina Tateo ◽  
Lisa Manuzzi ◽  
Andrea De Giglio ◽  
Claudia Parisi ◽  
Giuseppe Lamberti ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Cancer Biology ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Thymic Epithelial Tumors ◽  
Epithelial Tumors ◽  
New Treatment ◽  
Light Side ◽  
Thoracic Malignancies

Thymic epithelial tumors (TETs) are a group of rare thoracic malignancies, including thymic carcinomas (TC) and thymomas (Tm). Autoimmune paraneoplastic diseases are often observed in TETs, especially Tms. To date, chemotherapy is still the standard treatment for advanced disease. Unfortunately, few therapeutic options are available for relapsed/refractory TETs. In the last few years, the deepening of knowledge on thymus’ immunobiology and involved altered genetic pathways have laid the foundation for new treatment options in these rare neoplasms. Recently, the immunotherapy revolution has landed in TETs, showing both a dark and light side. Indeed, despite the survival benefit, the occurrence of severe autoimmune treatment-related adverse events has risen crescent uncertainty about the feasibility of immunotherapy in these patients, prone to autoimmunity for their cancer biology. In this review, after summarizing immunobiology and immunopathology of TETs, we discuss available data on immune-checkpoint inhibitors and future perspectives of this therapeutic strategy.

REVIVE study: Prospective observational study of efficacy and safety in chemotherapy (CTx) after progressive disease of nivolumab (NIV) therapy for metastatic gastric cancer (mGC).

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. TPS178-TPS178
Author(s):  
Yukiya Narita ◽  
Hirokazu Shoji ◽  
Sadayuki Kawai ◽  
Takuro Mizukami ◽  
Michio Nakamura ◽  
...  
Keyword(s):  
T Cells ◽  
Observational Study ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Group Performance ◽  
Checkpoint Inhibitors ◽  
Cytotoxic Agents ◽  
Efficacy And Safety ◽  
Inclusion Criteria ◽  
Prior Administration

TPS178 Background: Immune checkpoint inhibitors are drugs that block specific proteins produced by the immune system cells, such as T-cells; these proteins prevent T-cells from killing cancer cells. NIV is a standard care for pretreated mGC patients (pts), with increasing clinical use in Japan. Data from retrospective studies on various tumors have shown that after exposure to immune checkpoint inhibitors, the objective response rate to CTx potentially improves; however, enough data have not been accumulated. Although there are no recommended CTx regimen following NIV therapy, in a clinical setting, an irinotecan or oxaliplatin combination regimen (limited to cisplatin-refractory or cisplatin-intolerant pts) is frequently used as post-NIV CTx. This multicenter observational study aims to evaluate the efficacy and safety of CTx in NIV-refractory or NIV-intolerant mGC pts. Methods: We prospectively collect clinical and imaging data from NIV-pretreated mGC pts; these pts will be treated with cytotoxic agents. Pts who meet inclusion criteria A (histologically proven mGC pretreated with NIV, prior administration of a combination therapy of fluoropyrimidine plus platinum and taxanes, and written informed consent) at primary registration are registered. After primary registration, pts who meet inclusion criteria B [Eastern Cooperative Oncology Group Performance Status (ECOG PS 0-2), refractory or intolerant to NIV; prior administration of irinotecan monotherapy or oxaliplatin combination regimens and prior use of cisplatin; evaluable lesions according to RECIST ver. 1.1] at formal registration are registered. The primary endpoint is overall survival of NIV-pretreated mGC pts after CTx. For this study, we require 146 pts, with bilateral alpha = 0.05 and beta = 0.10, with a median threshold survival of 4.0 months and an expected median survival of 6.0 months. Therefore, we plan to enroll 200 pts, considering exclusions from the analysis; since May 2018, we have enrolled 27 pts. Clinical trial information: UMIN000032182.

Where do immune checkpoint inhibitors stand in the management of thymic epithelial tumors?

Immunotherapy ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 823-826
Author(s):  
Khalil Saleh ◽  
Nadine Khalifeh-Saleh ◽  
Hampig Raphael Kourie
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Thymic Epithelial Tumors ◽  
Epithelial Tumors

scholarly journals Immune Checkpoint Inhibitors in the Treatment of Renal Cancer: Current State and Future Perspective

2020 ◽  
Vol 21 (13) ◽  
pp. 4691
Author(s):  
Daniele Lavacchi ◽  
Elisa Pellegrini ◽  
Valeria Emma Palmieri ◽  
Laura Doni ◽  
Marinella Micol Mela ◽  
...  
Keyword(s):  
Gene Expression ◽  
Renal Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Single Agent ◽  
Gene Expression Pattern ◽  
Gene Expression Signature ◽  
Future Perspective ◽  
Immune Gene

Systemic treatment of renal cancer (RCC) has undergone remarkable changes over the past 20 years with the introduction of immunotherapeutic agents targeting programmed cell death (PD-1)/programmed death-ligand 1 (PD-L1) axis, as a single-agent or combined with anti-CTLA-4 monoclonal antibodies (MoAbs) or a multi-target vascular endothelial growth factor-(VEGF) tyrosine kinase inhibitor (TKI). In this paper, we review the main evidence on the use of Immune Checkpoint Inhibitors (ICIs) for RCC treatment from the first demonstration of activity of a nivolumab single agent in a phase I trial to the novel combination strategies (anti-PD-1 plus anti-CTLA4 or anti-PD-1 plus TKI). In addition, we discuss the use of anti-PD-1/PD-L1 agents in patients with non-clear cells and rare histological subtype RCC. Then, we critically examine the current findings in biomarkers that have been proposed to be prognostic or predictive to the response of immunotherapy including immune gene expression signature, B7-H1 expression, PBRM1 loss of function, PD-L1 expression, frame shift indel count, mutations in bromodomain-containing genes in patients with MiT family translocation RCC (tRCC), high expression of the T-effector gene signature, and a high myeloid inflammation gene expression pattern. To date, a single biomarker as a predictor of response has not been established. Since the dynamic behavior of the immune response and the different impact of ICI treatment on patients with specific RCC subtypes, the integration of multiple biomarkers and further validation in clinical trials are needed.

Endocrine adverse events related with immune checkpoint inhibitors: an update for clinicians

Immunotherapy ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 481-510 ◽  
Author(s):  
Maria V Deligiorgi ◽  
Mihalis I Panayiotidis ◽  
Dimitrios T Trafalis
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Clinical Success ◽  
Future Perspective ◽  
Programmed Cell Death 1 ◽  
Diagnostic Work ◽  
Work Up

Designated as scientific breakthrough of current decade, immune checkpoint inhibitors attenuate the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and the programmed cell death 1 (PD-1)/ligand 1 (PD-L1) pathways, depriving cancer cells of a key strategy of evasion from immunosurveillance. The reinvigoration of immune response translates into clinical success, inevitably entwined with a novel constellation of immune-related adverse events. The present review dissects the endocrine immune-related adverse events, emphasizing their unique profile featured by unpredictable onset, irreversibility, nonspecific symptoms, wide clinical spectrum and sophisticated diagnostic work-up. Guidelines advocate individualized decision-making process guided by clinicians' judgement. Future perspective should be governed by five principles – prevention, anticipation, detection, treatment, monitoring – aiming to gain the optimal profit diminishing immunotoxicity.

scholarly journals Dramatic Response in a Patient with Metastatic Gastric Cancer Using Trifluridine/Tipiracil after Rapid Disease Progression while on Nivolumab

2020 ◽  
Vol 13 (3) ◽  
pp. 1381-1386
Author(s):  
Kazuki Nozawa ◽  
Yukiya Narita ◽  
Waki Hosoda ◽  
Kei Muro
Keyword(s):  
Gastric Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Response Pattern ◽  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Laboratory Data ◽  
Metastatic Gastric Cancer ◽  
Cytotoxic Agents ◽  
Hyperprogressive Disease

The introduction of immune checkpoint inhibitors has redefined the treatment strategy and changed the way tumor assessments are made because of its response pattern. Studies have suggested that initiating chemotherapy after checkpoint inhibitors may have high anti-tumor activity in some cancer types. This response pattern has not been reported in patients with gastric cancer, and particularly for the combination of trifluridine/tipiracil. A 69-year-old man presented at follow-up for metastatic gastric cancer being treated with nivolumab, an anti-PD-1 antibody. Computed tomography of the liver showed a rapid 4-fold growth of the metastasis compared with baseline measurements taken while receiving paclitaxel and ramucirumab. It met the definition of a phenomenon called hyperprogressive disease. Nivolumab was discontinued, and he was switched to trifluridine/tipiracil. The liver metastasis was shrunk markedly after 2 months with improvement in his performance status and laboratory data. Sequential therapy starting with immune checkpoint inhibitors followed by cytotoxic agents such as trifluridine/tipiracil may have an apparent efficacy in gastric cancer even though prior immunotherapy demonstrates hyperprogressive disease.

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