scholarly journals Immune Checkpoint Inhibitors in Pre-Treated Gastric Cancer Patients: Results from a Literature-Based Meta-Analysis

2020 ◽  
Vol 21 (2) ◽  
pp. 448 ◽  
Author(s):  
Giandomenico Roviello ◽  
Silvia Paola Corona ◽  
Alberto D’Angelo ◽  
Pietro Rosellini ◽  
Stefania Nobili ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Eastern Cooperative Oncology Group ◽  
Metastatic Gastric Cancer ◽  
Control Group ◽  
Tumour Location

Immunotherapy has recently changed the treatment of several cancers. We performed a literature-based meta-analysis of randomised controlled trials to assess the efficacy of the novel immune checkpoint inhibitors (ICIs) in metastatic gastric cancer. The main outcome was overall survival. Based on age (cut-off agreed at 65 years), tumour location (gastric vs. gastro-oesophageal junction), programmed death-ligand 1 (PD-L1) status, sex and Eastern Cooperative Oncology Group (ECOG) status (1 vs. 0), we scheduled a subgroup analysis for the overall survival. Three studies were included in the analysis for a total of 1456 cases (811 cases were in the experimental group and 645 cases in the control group). The pooled analysis showed improved overall survival in the experimental arm in the absence of statistical significance (hazard ratio (HR) = 0.87, 95% CI: 0.64–1.18; p = 0.37). The subgroup of patients with PD-L1-positive tumours (HR = 0.82 vs. 1.04) and gastro-oesophageal junction cancer (HR = 0.82 vs. 1.04) showed a statistically significant advantage of overall survival. This study supports the efficacy of immune checkpoint inhibitors in the subgroup of patients with metastatic gastric cancer with PD-L1-positive and gastro-oesophageal junction tumour location. Future studies are needed with the aim of identifying reliable predictive biomarkers of ICI efficacy.

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.

scholarly journals Nivolumab as a representative of immune checkpoint inhibitors in late-line treatment for disseminated gastric cancer

2021 ◽  
pp. 96-107
Author(s):  
N. S. Besova
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Median Overall Survival ◽  
Checkpoint Inhibitors ◽  
Randomized Study ◽  
Objective Response ◽  
Malignant Tumours ◽  
Chemotherapy Drugs

Gastric cancer (GC) is one of the most common malignant tumours both in Russia and in the world. The drug therapy with consistent use of several therapy lines is the main method for treatment. The number of chemotherapy drugs, which are effective for the treatment of this type of malignant tumours, is limited; the range of targeted drugs is also narrow and includes trastuzumab in the first-line regimen for the treatment of HER2-positive gastric cancer and ramucirumab in the second-line regimen. Immune checkpoint inhibitors made a revolution in the treatment of many cancers. The efficacy of nivolumab, T cell inhibitory receptor of PD-L1, has been proven in the third-line regimen in disseminated gastric cancer. The ATTRACTION-2 randomized study showed that nivolumab significantly increased the median overall survival (from 4.14 to 5.26 months, p < 0.0001), progression-free survival (from 1.45 to 1.61 months, p < 0.0001); objective response with a median duration of 9.5 months was achieved in 11.2% of patients, stable disease in 29.1%. The median time to progression was 1.61 months. The toxicity of the treatment was quite low and led to discontinuation of treatment in only 1% (n = 4) of patients, who had previously received massive chemotherapy. Only patients from Asia took part in the ATTRACTION-2 study. However, its results were confirmed in the CheckMate-032 study in the non-Asian patient population: the objective response rate was 12%, the median DOR was 7.1 months, the median progressionfree survival was 1.4 months, and the median overall survival was 6.1 months. Nivolumab was effective for the treatment of MSI-H and MSS, PD-L1-positive and PD-L1-negative tumours. Nivolumab is a recognized and well-tolerated standard of late-line therapy in disseminated gastric cancer. The range of indications for its prescription will be expanded in the nearest future.

scholarly journals Association of Immune Related Adverse Events With Efficacy of Immune Checkpoint Inhibitors and Overall Survival in Cancers: A Systemic Review and Meta-analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Yong Fan ◽  
Wenhui Xie ◽  
Hong Huang ◽  
Yunxia Wang ◽  
Guangtao Li ◽  
...  
Keyword(s):  
Overall Survival ◽  
Adverse Events ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Tumor Response ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Pooled Data ◽  
Cancer Types

ObjectivesImmune checkpoint inhibitors (ICIs) have brought impressive benefits to cancer patients, however often accompanied with immune-related adverse events (irAEs). We aimed to investigate the association of irAEs with efficacy and overall survival in cancer patients treated by ICIs, and further quantify the association by stratifying subgroups.MethodsPubMed, EMBASE and Cochrane library from database inception to 29 August 2019 were systematically searched. Articles reporting association of objective response rate (ORR), progression-free survival (PFS), overall survival (OS) with irAEs in cancer patients treated with approved ICIs were included. Adjusted odds ratios (OR) with 95% confidential intervals (CIs) were calculated for ORR, and hazard ratios (HR) were used for PFS and OS.ResultsA total of 52 articles comprising 9,156 patients were included. Pooled data demonstrated a statistically significant greater probability of achieving objective tumor response for patients with irAEs compared to those without (OR 3.91, 95% CI 3.05–5.02). In overall meta-analysis, patients who developed irAEs presented a prolonged PFS (HR 0.54; 95% CI 0.46–0.62) and OS (HR 0.51; 95% CI 0.41–0.59). More specifically, irAEs in certain cancer types (NSCLC and melanoma) and organs (skin and endocrine) were robustly associated with better clinical outcomes, while this association needs further verification regarding other tumors. High grade toxicities (G3–5) were not associated with a significantly favorable PFS or OS. Additionally, the association between irAEs and clinical benefit seemed to be more definite in patients receiving PD-(L)1 blockade than CTLA-4 blockade. Pooled data from landmark analyses displayed consistent results.ConclusionsThe occurrence of irAEs predicted improved tumor response and better survival in overall cancer patients treated with ICIs. Notably, the association stayed robust in certain cancer types (NSCLC and melanoma) and organ-specific irAEs (skin and endocrine).

scholarly journals Results from a meta-analysis of immune checkpoint inhibitors in first-line renal cancer patients: does PD-L1 matter?

2019 ◽  
Vol 11 ◽  
pp. 175883591986190 ◽  
Author(s):  
Giandomenico Roviello ◽  
Silvia Paola Corona ◽  
Gabriella Nesi ◽  
Enrico Mini
Keyword(s):  
Overall Survival ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Pooled Analysis ◽  
First Line

Background: The aim of this study was to perform a literature-based meta-analysis to assess the efficacy of the novel immune checkpoint inhibitors (ICIs) in first-line metastatic renal cell carcinoma (RCC), focusing on the predictive role of PD-L1 expression. Methods: The primary outcome was overall survival, and secondary outcomes were progression-free survival (PFS) and objective response. We planned a subgroup analysis for overall survival according to PD-L1 status. Results: Five studies were included in the analysis for a total of 4063 cases. Overall survival was greater in PD-L1 positive tumours (HR = 0.49, 95% CI: 0.36–0.67; p < 0.001). The pooled analysis of the unselected cases showed a statistically significative improvement in PFS with the use of ICIs (HR = 0.85, 95% CI: 0.72–0.99; p = 0.04) and we found a greater PFS benefit (HR = 0.65, 95% CI: 0.57–0.74; p < 0.001) in patients with PD-L1 positive tumours. Conclusions: This study supports the efficacy of ICIs and, although a significant clinical benefit has been reported in PD-L1 negative patients, a greater efficacy of ICIs was observed in PD-L1 positive patients. More prospective randomized studies are needed to clarify the role of PDL-1 status in metastatic RCC treated with ICIs.

Clinical significance of tumour mutation burden in immunotherapy across multiple cancer types: an individual meta-analysis

2020 ◽  
Vol 50 (9) ◽  
pp. 1023-1031
Author(s):  
Zhenyu Yang ◽  
Shiyou Wei ◽  
Yulan Deng ◽  
Zihuai Wang ◽  
Lunxu Liu
Keyword(s):  
Overall Survival ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Cancer Type ◽  
Free Survival ◽  
Mutation Burden

Abstract Background Biomarkers for stratifying patients that could benefit from immune checkpoint inhibitors are necessary. Tumour mutation burden has recently become a promising biomarker in cancer, but the associations between tumour mutation burden and outcomes of immune checkpoint inhibitors treatment were not well-documented in present studies. Methods We searched PubMed, Web of Science and EMBASE databases up to 1 October 2019. Studies evaluated the association between tumour mutation burden and clinical outcomes were included. Hazard ratios and odds ratios were applied to estimate the association of tumour mutation burden score with overall survival, progression-free survival and response rate, respectively. The best cut-off value was chosen by best discriminated overall survival using Contal and O’Quigley method. Results Twenty-two studies involving 6171 patients in diverse cancers were included. The individual participant data meta-analysis demonstrated that high tumour mutation burden was associated with better overall survival (HR = 0.57, 95% CI = 0.50–0.64) and progression-free survival (HR = 0.50, 95% CI = 0.40–0.63) and higher response rate. The best cut-off values in each cancer type were 17.7/MB in non-small cell lung cancer, 7.9/MB in bladder cancer, 6.1/MB in melanoma, 12.3/MB in colorectal cancer, 6.9/MB in esophagogastric cancer, 10.5/MB in head and neck cancer. The pooled meta-analysis showed the prognosis value was robust and the sensitivity, specificity and area under the receiver operating characteristic curves in predicting response rates were 0.63, 0.71 and 0.73, respectively. Conclusions The present meta-analysis indicates tumour mutation burden is a promising predictor of immune checkpoint inhibitors therapy but the cut-off value differs in different cancers.

scholarly journals Current status and future potential of predictive biomarkers for immune checkpoint inhibitors in gastric cancer

ESMO Open ◽  
2020 ◽  
Vol 5 (4) ◽  
pp. e000791 ◽  
Author(s):  
Byung Woog Kang ◽  
Ian Chau
Keyword(s):  
Gastric Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Gene Expression Signature ◽  
Predictive Biomarkers ◽  
Predictive Biomarker ◽  
Metastatic Gastric Cancer ◽  
Scientific Data ◽  
Current Status

Immunotherapy is revolutionising cancer treatment and has already emerged as standard treatment for patients with recurrent or metastatic gastric cancer (GC). Recent research has been focused on identifying robust predictive biomarkers for GC treated with immune checkpoint inhibitors (ICIs). The expression of programmed cell death protein-ligand-1 (PD-L1) is considered a manifestation of immune response evasion, and several studies have already reported the potential of PD-L1 expression as a predictive parameter for various human malignancies. Meanwhile, based on comprehensive molecular characterisation of GC, testing for Epstein-Barr virus and microsatellite instability is a potential predictive biomarker. Culminating evidence suggests that novel biomarkers, such as the tumour mutational burden and gene expression signature, could indicate the success of treatment with ICIs. However, the exact roles of these biomarkers in GC treated with ICIs remain unclear. Therefore, this study reviews recent scientific data on current and emerging biomarkers for ICIs in GC, which have potential to improve treatment outcomes.

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.

A comprehensive meta-analysis of endocrine immune-related adverse events of immune checkpoint inhibitors and outcomes in head and neck cancer and lung cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14096-e14096 ◽  
Author(s):  
Cristiane Jeyce Gomes-Lima ◽  
John Kwagyan ◽  
Fred King ◽  
Stephen J Fernandez ◽  
Kenneth D Burman ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Head And Neck Cancer ◽  
Adverse Events ◽  
Neck Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Grade 3

e14096 Background: Immune checkpoint inhibitors (ICPi) have emerged as an effective treatment for a variety of cancers. However, important immune-related adverse events (irAEs) can occur. The aim of this study was to determine the prevalence of endocrine irAEs in patients with head and neck cancer and lung cancer that have used a ICPi and outcomes. Methods: A systematic literature review was performed within PubMed and EMBASE databases. Search terms included “durvalumab”, “atezolizumab”, “nivolumab”, “pembrolizumab”, “ipilimumab”, “head & neck cancer”, “lung cancer”. Studies published before September 2018 were included. The search was limited to randomized controlled trials (RCTs) phase III written in English. Data were extracted about patient characteristics, interventions, overall survival (OS), progression free survival (PFS), and endocrine irAEs. A summary hazard ratio (HR) and 95% confidence interval were calculated using the software Comprehensive Meta-Analysis and a scatter plot was generated. Results: Twelve RCTs comprising 7060 patients were reviewed; 3815 used an ICPi (treatment arm). The mean follow-up time of 12.2 months ± 7.1 SD. The survival rate of the treatment arm was enhanced (HR, 0.75; 95% CI, 0.70-0.80), compared to the alternate arm. Similarly, the PFS of the treatment arm was improved (HR, 0.77; 95% CI, 0.72-0.81) but with a higher incidence of endocrine irAEs. The most common endocrine irAE reported was hypothyroidism;193 patients in the treatment arm vs. 29 in the alternate arm (p < 0.001); grade 3/4 AE was observed in 10 patients vs. 1 patient, respectively. Other endocrine irAEs were reported in 168 patients in the treatment arm vs. 26 patients in the alternate arm (p < 0.001); grade 3/4 AE was observed in 28 patients vs. 3 patients, respectively. A significant positive correlation between endocrine irAEs and OS was observed (p = 0.019). Conclusions: ICPi are a powerful tool in the treatment of cancer. The prevalence of endocrine irAEs in this meta-analysis was 9%. There is evidence of improved overall survival in patients who developed endocrine irAEs. Further studies are needed to correlate the development of irAEs and OS advantage.

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