Search results for " checkpoint inhibitors"

Prognostic value of Thyroid Transcription Factor-1 expression in lung adenocarcinoma in patients treated with anti PD-1/PD-L1.

2021

ABSTRACT Anti-PD1/PD-L1-directed immune checkpoint inhibitors are game changers in advanced non-small-cell lung cancer, but biomarkers are lacking. The aim of our study was to find clinically relevant biomarkers of the efficacy of ICI in non-squamous NSCLC. We conducted a retrospective study of patients receiving ICI for advanced non squamous NSCLC in two cohorts. For a subset of patients, RNAseq data were generated on tumor biopsy taken before ICI. The primary end point was progression-free survival under ICI. Secondary end point was overall survival from ICI initiation. In the cohort, we studied 231 patients. Clinico-pathological characteristics included KRAS mutant status (n = 88), TTF1-…

Evaluation of atezolizumab immunogenicity: Efficacy and safety (Part 2).

2022

Abstract Antibody therapeutics can be associated with unwanted immune responses resulting in the development of anti‐drug antibodies (ADA). Optimal methods to evaluate the potential effects of ADA on clinical outcomes in oncology are not well established. In this study, we assessed efficacy and safety, based on ADA status, in patients from over 10 clinical trials that evaluated the immune checkpoint inhibitor atezolizumab as a single agent or as combination therapy for several types of advanced cancers. ADA can only be observed post randomization, and imbalances in baseline prognostic factors can confound the interpretation of ADA impact. We applied methodology to account for the confoundin…

French Endocrine Society Guidance on endocrine side effects of immunotherapy.

2018

The management of cancer patients has changed due to the considerably more frequent use of immune checkpoint inhibitors (ICPIs). However, the use of ICPI has a risk of side effects, particularly endocrine toxicity. Since the indications for ICPI are constantly expanding due to their efficacy, it is important that endocrinologists and oncologists know how to look for this type of toxicity and how to treat it when it arises. In view of this, the French Endocrine Society initiated the formulation of a consensus document on ICPI-related endocrine toxicity. In this paper, we will introduce data on the general pathophysiology of endocrine toxicity, and we will then outline expert opinion focusing…

Outcome of patients with elevated LDH treated with first-line targeted therapy (TT) or PD-1 based immune checkpoint inhibitors (ICI)

2019

Abstract Background Elevated LDH is a known predictive and prognostic factor correlating with poor response rates and survival in patients (pts) with metastatic melanoma (MM) treated with targeted therapy (BRAF plus MEK inhibitors, TT) or immune checkpoint inhibitors (ICI). Whether TT or ICI in this subgroup of pts is more beneficial is unknown. Methods Pts with MM and elevated LDH who started first-line therapy between March 2016 and June 2017 were retrospectively identified from 25 melanoma centers. The cohort was divided into 2 groups: pts receiving TT first-line (TT group) and ICI first-line (ICI group). Primary endpoints were overall response rate (ORR), progression-free survival (PFS)…

165P Baseline circulating myeloid-derived suppressor cells correlate with neutrophil-to-lymphocyte ratio and overall survival in advanced non-small c…

2021

Efficacy of Immune Checkpoint Inhibitors Alone or in Combination With Chemotherapy in NSCLC Harboring ERBB2 Mutations

2021

Abstract Introduction In contrast to other driver mutations, no targeted therapies have yet been approved in ERBB2-mutated NSCLC (HER2mu NSCLC). Nevertheless, several compounds have revealed promising early efficacy data, which need to be evaluated in the context of current standard approaches. Although data on the efficacy of immune checkpoint inhibitors (ICIs) in second or subsequent lines of treatment remain limited and conflicting, there are virtually no data on patient outcome under ICI/platinum-doublet combinations in the first-line setting. Methods We retrospectively evaluated outcomes of patients with HER2mu NSCLC treated with ICI alone or in combination with chemotherapy within the…

The quest for precision oncology with immune checkpoint inhibitors for hepatocellular carcinoma

2022

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Programmed cell death 1 genetic variant and liver damage in nonalcoholic fatty liver disease

2023

Background and aims: Programmed cell death 1/programmed cell death-ligand 1 (PD-1/PDL-1) axis has been reported to modulate liver inflammation and progression to hepatocellular carcinoma (HCC) in patients with nonalcoholic fatty liver disease (NAFLD). Here, we examined whether the PDCD1 variation is associated with NAFLD severity in individuals with liver biopsy. Methods: We examined the impact of PDCD1 gene variants on HCC, as robust severe liver disease phenotype in UK Biobank participants. The strongest genetic association with the rs13023138 G>C variation was subsequently tested for association with liver damage in 2889 individuals who underwent liver biopsy for suspected nonalcoholi…

Side effect management during immune checkpoint blockade using CTLA-4 and PD-1 antibodies for metastatic melanoma – an update

2020

CTLA-4 and PD-1 play a key role in tumor-induced downregulation of lymphocytic immune responses. Immune checkpoint inhibitors have been shown to alter the immune response to various cancer types. Anti-CTLA-4 and anti-PD-1 antibodies affect the interaction between tumor, antigen-presenting cells and T lymphocytes. Clinical studies of the anti-CTLA-4 antibody ipilimumab and the anti-PD-1 antibodies nivolumab and pembrolizumab have provided evidence of their positive effects on overall survival in melanoma patients. Combined treatment using ipilimumab and nivolumab has been shown to achieve five-year survival rates of 52 %. Such enhancement of the immune response is inevitably associated with …

Emerging Therapies in Pheochromocytoma and Paraganglioma: Immune Checkpoint Inhibitors in the Starting Blocks

2021

Pheochromocytoma and paraganglioma are neuroendocrine neoplasms, originating in the adrenal medulla and in parasympathetic and sympathetic autonomic nervous system ganglia, respectively. They usually present as localized tumours curable with surgery. However, these tumours may exhibit heterogeneous clinical course, ranging from no/minimal progression to aggressive (progressive/metastatic) behavior. For this setting of patients, current therapies are unsatisfactory. Immune checkpoint inhibitors have shown outstanding results for several types of solid cancers. We therefore aimed to summarize and discuss available data on efficacy and safety of current FDA-approved immune checkpoint inhibitor…