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 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.

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 Clinical Outcomes of Patients With Metastatic Urothelial Carcinoma After Progression to Immune Checkpoint Inhibitors: A Retrospective Analysis by the Meet-Uro Group (Meet-URO 1 Study)

2021 ◽  
Vol 15 ◽  
pp. 117955492110216
Author(s):  
Melissa Bersanelli ◽  
Sebastiano Buti ◽  
Alessio Cortellini ◽  
Marco Bandini ◽  
Giuseppe Luigi Banna ◽  
...  
Keyword(s):  
Overall Survival ◽  
Immune Checkpoint ◽  
Objective Response Rate ◽  
Immune Checkpoint Inhibitors ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Line Therapy ◽  
Programmed Death ◽  
Platinum Based Chemotherapy

Background: Immune checkpoint inhibitors (ICIs) are currently the standard of care for metastatic urothelial cancer (mUC) after the failure of previous platinum-based chemotherapy. The choice of further therapy after ICI progression is a new challenge, and scarce data support it. We aimed to examine the outcomes of mUC patients after progression to ICI, especially when receiving chemotherapy. Methods: Data were retrospectively collected from clinical records of mUC patients whose disease progressed to anti-programmed death 1 (PD-1)or programmed death ligand 1 (PD-L1) therapy at 14 Italian centers. Patients were grouped according to ICI therapy setting into SALVAGE (ie, ICI delivered ⩾ second-line therapy after platinum-based chemotherapy) and NAÏVE (ie, first-line therapy) groups. Progression-free survival (PFS) and overall survival (OS) rates were calculated using the Kaplan-Meier method and compared among subgroups. Cox regression assessed the effect of treatments after progression to ICI on OS. Objective response rate (ORR) was calculated as the sum of partial and complete radiologic responses. Results: The study population consisted of 201 mUC patients who progressed after ICI: 59 in the NAÏVE cohort and 142 in the SALVAGE cohort. Overall, 52 patients received chemotherapy after ICI progression (25.9%), 20 (9.9%) received ICI beyond progression, 115 (57.2%) received best supportive care only, and 14 (7.0%) received investigational drugs. Objective response rate to chemotherapy in the post-ICI setting was 23.1% (28.0% in the NAÏVE group and 18.5% in the SALVAGE group). Median PFS and OS to chemotherapy after ICI-PD was 5 months (95% confidence interval [CI]: 3-11) and 13 months (95% CI: 7-NA) for the NAÏVE group; 3 months (95% CI: 2-NA) and 9 months (95% CI: 6-NA) for the SALVAGE group, respectively. Overall survival from ICI initiation was 17 months for patients receiving chemotherapy (hazard ratio [HR] = 0.09, p < 0.001), versus 8 months for patients receiving ICI beyond progression (HR = 0.13, p < 0.001), and 2 months for patients who did not receive further active treatment ( p < 0.001). Conclusions: Chemotherapy administered after ICI progression for mUC patients is advisable irrespective of the treatment line.

scholarly journals LMD-10. The role of immune checkpoint inhibitors in leptomeningeal disease: a systematic review

2021 ◽  
Vol 3 (Supplement_3) ◽  
pp. iii9-iii9
Author(s):  
Paolo Palmisciano ◽  
Ali S Haider ◽  
Chibueze D Nwagwu ◽  
Waseem Wahood ◽  
Navraj S Sagoo ◽  
...  
Keyword(s):  
Overall Survival ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Median Overall Survival ◽  
Checkpoint Inhibitors ◽  
Leptomeningeal Disease ◽  
Mri Findings ◽  
Primary Tumors ◽  
Advanced Malignancy

Abstract Background Leptomeningeal disease (LMD) is a devastating complication of advanced malignancy with a poor prognosis and limited therapeutic options. Whether immune checkpoint inhibitors (ICIs) alter disease course is unknown. Methods We searched PubMed, EMBASE, Scopus, Cochrane, and clinicaltrials.gov according to PRISMA guidelines to analyze the therapeutic role and toxicity profiles of ICIs in the management of LMD. Studies reporting clinical outcome data of patients with LMD treated with ICIs were included. A comprehensive review of clinical characteristics and survival analysis was conducted. Results We included 14 studies encompassing 61 patients. The median age at LMD diagnosis was 57 years (female=63.9%). Lung cancer (44.3%), breast cancer (27.9%), and melanoma (23.0%) were the most frequent primary tumors. Parenchymal brain metastases occurred in 37 patients, mostly treated with radiotherapy (83.3%). LMD most frequently presented with headache (42.1%) and was diagnosed by MRI findings (leptomeningeal T1-contrast enhancement: 96.7%) and/or positive cerebrospinal fluid cytology (86.5%). Patients received ICIs for a median duration of 7 months (range, 0.5–58.0): pembrolizumab (49.2%), nivolumab (32.8%), and/or ipilimumab (18.0%). The most common concurrent LMD treatments were radiotherapy (54.7%) and steroids (35.7%). Radiological responses at 6-months were complete (33.3%) and partial response (12.5%), stable disease (33.3%), and progression (20.8%). 22 patients developed ICI-related adverse events, mostly mild (100%) and uncommonly severe (15.6%). Median progression-free survival was 5.1 months, median overall survival was 6.3 months, and 12-month survival was 32.1%. Survival was correlated with ICIs (P=0.042), but not with primary tumors (P=0.144). Patients concurrently receiving steroids showed worse survival (P=0.040), with a median overall survival of 1.9 months. Conclusion ICI therapy shows promise and appears to be well-tolerated in patients with LMD. Concurrent use of steroids is associated with worse survival. The role of ICIs in the multimodal management of LMD and their combination with steroids requires further analysis.

scholarly journals Identification of an Immune-Related LncRNA Signature in Gastric Cancer to Predict Survival and Response to Immune Checkpoint Inhibitors

2021 ◽  
Vol 9 ◽  
Author(s):  
Zuoyou Ding ◽  
Ran Li ◽  
Jun Han ◽  
Diya Sun ◽  
Lei Shen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Risk Group ◽  
Checkpoint Inhibitors ◽  
High Risk Group ◽  
Low Risk ◽  
Predictive Capability ◽  
Invasive Capacity

Immune microenvironment in gastric cancer is closely associated with patient’s prognosis. Long non-coding RNAs (lncRNAs) are emerging as key regulators of immune responses. In this study, we aimed to construct a prognostic model based on immune-related lncRNAs (IRLs) to predict the overall survival and response to immune checkpoint inhibitors (ICIs) of gastric cancer (GC) patients. The IRL signature was constructed through a bioinformatics method, and its predictive capability was validated. A stratification analysis indicates that the IRL signature can distinguish different risk patients. A nomogram based on the IRL and other clinical variables efficiently predicted the overall survival of GC patients. The landscape of tumor microenvironment and mutation status partially explain this signature’s predictive capability. We found the level of cancer-associated fibroblasts, endothelial cells, M2 macrophages, and stroma cells was high in the high-risk group, while the number of CD8+ T cells and T follicular helper cells was high in the low-risk group. Immunophenoscore (IPS) is validated for ICI response, and the IRL signature low-risk group received higher IPS, representing a more immunogenic phenotype that was more inclined to respond to ICIs. In addition, we found RNF144A-AS1 was highly expressed in GC patients and promoted the proliferation, migration, and invasive capacity of GC cells. We concluded that the IRL signature represents a novel useful model for evaluating GC survival outcomes and could be implemented to optimize the selection of patients to receive ICI treatment.

scholarly journals EVALUATION OF THE EFFECTIVENESS OF MODERN IMMUNOTHERAPY

2020 ◽  
Vol 66 (3) ◽  
pp. 211-217
Author(s):  
A. Oganesian ◽  
Svetlana Protsenko ◽  
Irina Baldueva ◽  
Anna Semenova ◽  
Yekaterina Anokhina ◽  
...  
Keyword(s):  
Overall Survival ◽  
Treatment Option ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Malignant Tumors ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Histological Subtypes ◽  
Research Results ◽  
Promising Treatment

Immune checkpoint inhibitors are the most promising treatment option for many histological subtypes of malignant tumors, providing a long objective response and an increase in overall survival. Currently, there is growing evidence of the specific heterogeneity of clinical and radiological responses to immunotherapy, such as pseudoprogression and hyperprogression. In connection with the presence of these phenomena, the clinicians have a serious question about the need to allocate a certain cohort of patients for whom therapy with immuno-oncological drugs will be most effective and safe. This review demonstrates research results describing mentioned phenomena.

scholarly journals How to Best Exploit Immunotherapeutics in Advanced Gastric Cancer: Between Biomarkers and Novel Cell-Based Approaches

2021 ◽  
Vol 10 (7) ◽  
pp. 1412
Author(s):  
Michele Ghidini ◽  
Angelica Petrillo ◽  
Andrea Botticelli ◽  
Dario Trapani ◽  
Alessandro Parisi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Predictive Biomarkers ◽  
Clinical Implementation ◽  
T Cell Therapy ◽  
Dismal Prognosis

Despite extensive research efforts, advanced gastric cancer still has a dismal prognosis with conventional treatment options. Immune checkpoint inhibitors have revolutionized the treatment landscape for many solid tumors. Amongst gastric cancer subtypes, tumors with microsatellite instability and Epstein Barr Virus positive tumors provide the strongest rationale for responding to immunotherapy. Various predictive biomarkers such as mismatch repair status, programmed death ligand 1 expression, tumor mutational burden, assessment of tumor infiltrating lymphocytes and circulating biomarkers have been evaluated. However, results have been inconsistent due to different methodologies and thresholds used. Clinical implementation therefore remains a challenge. The role of immune checkpoint inhibitors in gastric cancer is emerging with data from monotherapy in the heavily pre-treated population already available and studies in earlier disease settings with different combinatorial approaches in progress. Immune checkpoint inhibitor combinations with chemotherapy (CT), anti-angiogenics, tyrosine kinase inhibitors, anti-Her2 directed therapy, poly (ADP-ribose) polymerase inhibitors or dual checkpoint inhibitor strategies are being explored. Moreover, novel strategies including vaccines and CAR T cell therapy are also being trialed. Here we provide an update on predictive biomarkers for response to immunotherapy with an overview of their strengths and limitations. We discuss clinical trials that have been reported and trials in progress whilst providing an account of future steps needed to improve outcome in this lethal disease.

scholarly journals Ipilimumab and nivolumab/pembrolizumab in advanced hepatocellular carcinoma refractory to prior immune checkpoint inhibitors

2021 ◽  
Vol 9 (2) ◽  
pp. e001945 ◽  
Author(s):  
Jeffrey Sum Lung Wong ◽  
Gerry Gin Wai Kwok ◽  
Vikki Tang ◽  
Bryan Cho Wing Li ◽  
Roland Leung ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Acquired Resistance ◽  
Survival Rates ◽  
Advanced Hepatocellular Carcinoma ◽  
Primary Resistance ◽  
Advanced Hcc

BackgroundProgrammed cell death protein 1 (PD-1) pathway blockade with immune checkpoint inhibitors (ICIs) is a standard therapy in advanced hepatocellular carcinoma (HCC) nowadays. No strategies to overcome ICI resistance have been described. We aimed to evaluate the use of ipilimumab and anti-PD-1 ICIs (nivolumab or pembrolizumab) combinations in patients with advanced HCC with progression on prior ICIs.MethodsPatients with advanced HCC with documented tumor progression on prior ICIs and subsequently received ipilimumab with nivolumab/pembrolizumab were analyzed. Objective response rate (ORR), median duration of response (DOR), time-to-progression (TTP), overall survival (OS), and treatment-related adverse events (TRAEs) were assessed.ResultsTwenty-five patients were included. The median age was 62 (range: 51–83). About 68% were of Child-Pugh (CP) Grade A and 48% had primary resistance to prior ICI. At median follow-up of 37.7 months, the ORR was 16% with a median DOR of 11.5 months (range: 2.76–30.3). Three patients achieved complete response. The median TTP was 2.96 months (95% CI: 1.61 to 4.31). Median OS was 10.9 months (95% CI: 3.99 to 17.8) and the 1 year, 2 year and 3 year survival rates were 42.4%, 32.3% and 21.6%, respectively. The ORR was 16.7% in primary resistance group and 15.4% in acquired resistance group (p=1.00). All responders were of CP A and Albumin-Bilirubin (ALBI) Grade 1 or 2. CP and ALBI Grades were significantly associated with OS (p=0.006 and p<0.001, respectively). Overall, 52% of patients experienced TRAEs and 12% experienced Grade 3 or above TRAEs.ConclusionsIpilimumab and nivolumab/pembrolizumab can achieve durable antitumor activity and encouraging survival outcomes with acceptable toxicity in patients with advanced HCC who had prior treatment with ICIs.

scholarly journals 363 Vactosertib and durvalumab as second or later line treatment for PD-L1 positive non-small cell lung cancer: interim result

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A388-A388
Author(s):  
Byoung Chul Cho ◽  
Ki Hyeong Lee ◽  
Ji-Youn Han ◽  
Byoung Yong Shim ◽  
Hye Ryun Kim ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Objective Response Rate ◽  
Immune Checkpoint Inhibitors ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Platinum Based Chemotherapy ◽  
Number Of Patients ◽  
Anti Tumor Activity

BackgroundTargeting transforming growth factor-β (TGF-β) is reported to augment the efficacy of immune checkpoint inhibitors (ICIs) through either enhanced anti-tumor immunity or the correction of tumor microenvironment (TME). Therefore, the combination of vactosertib, a highly selective TGF-β RI kinase inhibitor, and durvalumab is anticipated to improve anti-tumor activity of the ICI. A phase 1b/2a study was conducted to evaluate the combination of vactosertib and durvalumab in patients with advanced NSCLC who progressed after platinum-based chemotherapy.MethodsPatients were treated with vactosertib at a dose of 200 mg twice daily (five days on and two days off) and durvalumab at a dose of 1500 mg every four weeks. Eligible patients were ≥19 years old with good performance status (ECOG 0–1) and have no prior exposure to immune checkpoint inhibitors or other TGF- β R1 kinase inhibitors. The objectives of this analysis were to evaluate the safety, antitumor activity including objective response rate (ORR), duration of response (DOR), and time to response (TTR) as well as circulating pharmacodynamic biomarkers related to TGF-β signaling. Response was assessed per RECIST (v1.1).ResultsBy August 4 2020, twenty-six PD-L1 positive (SP263 assay) patients were analyzed. Median age was 61.5 years (range 48–83), 69.2% were male, median number of previous lines of chemotherapy was 1 (range 1–4), and all patients were PD-L1 positive (15 patients with PD-L1≥25% and 11 patients with PD-L1 1–24%). The most frequently reported treatment-related adverse events (TRAE) were itching (38.5%) and skin rash (34.6%), but no Gr≥3 itching and rash were observed. Each case of the following was reported as Grade 3 TRAEs: adrenal insufficiency, anemia, and pneumonitis; Grade 4 TRAE, CPK increase, was observed in one patient. Objective response rate was 30.8% and 40.0% in patients with PD-L1≥1% and ≥25% respectively. Circulating PAI-1 and CTGF evaluated in 15 patients decreased significantly on Cycle 1 day 5. Ongoing biomarker results will be presented.ConclusionsThe combination of vactosertib and durvalumab has demonstrated a manageable safety profile and encouraging anti-tumor activity as a potential therapeutic strategy in patients with advanced NSCLC. The efficacy outcomes of this combination in a larger number of patients with advanced NSCLC will be followed.Trial RegistrationNCT03732274Ethics ApprovalThe study was approved by Ethics Board of Severance Hospital (4-2018-0892), National Cancer Center (NCC2019-0057), St. Vincent’s Hospital (VC19MDDF0205), and Chungbuk National University Hospital (2019-08-015).

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