Outcomes following immunotherapy re-challenge after immune-related adverse event: systematic review and meta-analysis

Immunotherapy ◽  
2020 ◽  
Vol 12 (16) ◽  
pp. 1183-1193
Author(s):  
Robin Park ◽  
Laercio Lopes ◽  
Anwaar Saeed
Keyword(s):  
Systematic Review ◽  
Immune Checkpoint ◽  
Odds Ratio ◽  
Immune Checkpoint Inhibitors ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Objective Response ◽  
Cochrane Database ◽  
Grade 3

Background: Given the inconclusive evidence behind the safety and efficacy of immune checkpoint inhibitors re-challenge, herein, we have conducted a systematic review and meta-analysis to synthesize available data. Results/methodology: PubMed, Embase, Cochrane Database, and ASCO and ESMO were searched for studies published from conception to March 2020. Pooled incidence of recurrent immune-related adverse events (irAEs), objective response rates, and odds ratios for irAEs at initial versus re-treatment were calculated. Overall, 437 patients (ten studies) were included. Incidence of any grade, grade 3/4, and steroid-requiring recurrent irAEs were 47%, 13.2%, and 26% respectively. Objective response rate in previous non-responders was 12.5% (5.8–24.8%). Odds ratio for severe irAEs was 0.28 (0.11–0.72) and steroid-requiring irAEs 0.19 (0.06–0.56). Discussion/conclusion: This analysis suggests that immune checkpoint inhibitors re-challenge is safe and potentially efficacious.

scholarly journals Systematic Review and Network Meta-Analysis of Immune Checkpoint Inhibitors in Combination with Chemotherapy as a First-Line Therapy for Extensive-Stage Small Cell Carcinoma

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3629
Author(s):  
Hsiao-Ling Chen ◽  
Yu-Kang Tu ◽  
Hsiu-Mei Chang ◽  
Tai-Huang Lee ◽  
Kuan-Li Wu ◽  
...  
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Small Cell ◽  
Randomized Controlled ◽  
Extensive Stage ◽  
Grade 3

Patients with extensive-stage small cell lung cancer (ED-SCLC) have a very short survival time even if they receive standard cytotoxic chemotherapy with etoposide and platinum (EP). Several randomized controlled trials have shown that patients with ED-SCLC who received a combination of EP plus immune checkpoint inhibitors (ICIs) had superior survival compared with those who received EP alone. We conducted a systematic review and network meta-analysis to provide a ranking of ICIs for our primary endpoints in terms of overall survival (OS), progression free survival (PFS), and objective response rate (ORR), as well as our secondary endpoint in terms of adverse events. The fractional polynomial model was used to evaluate the adjusted hazard ratios for the survival indicators (OS and PFS). Treatment rank was estimated using the surface under the cumulative ranking curve (SUCRA), as well as the probability of being best (Prbest) reference. EP plus nivolumab, atezolizumab or durvalumab had significant benefits compared with EP alone in terms of OS (Hazard Ratio HR = 0.67, 95% Confidence Interval CI = 0.46–0.98 for nivolumab, HR = 0.70, 95% CI = 0.54–0.91 for atezolizumab, HR = 0.73, 95% CI = 0.59–0.90 for durvalumab) but no significant differences were observed for pembrolizumab or ipilimumab. The probability of nivolumab being ranked first among all treatment arms was highest (SCURA = 78.7%, Prbest = 46.7%). All EP plus ICI combinations had a longer PFS compared with EP alone (HR = 0.65, 95% CI = 0.46–0.92 for nivolumab, HR = 0.77, 95% CI = 0.61–0.96 for atezolizumab, HR = 0.78, 95% CI = 0.65–0.94 for durvalumab, HR = 0.75, 95% CI = 0.61–0.92 for pembrolizumab), and nivolumab was ranked first in terms of PFS (SCURA = 85.0%, Prbest = 66.8%). In addition, nivolumab had the highest probability of grade 3–4 adverse events (SUCRA = 84.8%) in our study. We found that nivolumab had the best PFS and OS in all combinations of ICIs and EP, but nivolumab also had the highest probability of grade 3–4 adverse events in our network meta-analysis. Further head-to head large-scale phase III randomized controlled studies are needed to verify our conclusions.

Effect of immunotherapy on survival outcomes in prostate cancer: Systematic review and meta-analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e17030-e17030
Author(s):  
Vinod solipuram ◽  
Kishor Pokharel ◽  
Bhanu Prasad Venkatesulu ◽  
Harideep Samanapally
Keyword(s):  
Prostate Cancer ◽  
Systematic Review ◽  
Overall Survival ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Standard Treatment ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Grade 3

e17030 Background: Prostate cancer is one of the leading cancers in men with an estimated 191,930 new cases in 2020 in the USA alone. Treatment options for metastatic castration resistant prostate cancer (mCRPC) have evolved in recent years. Immunotherapy involving vaccines like sipuleucel-T, PROSTVAC and immune checkpoint inhibitors have been evaluated in these patients. We present a systematic review and meta-analysis of the randomized controlled trials (RCTs) testing the effect of immunotherapy in mCRPC. Methods: A systematic search was performed using PubMed, Embase and the Cochrane library without language limitations from inception to January 3, 2021. The primary outcome was overall survival (OS) and secondary outcomes were progression free survival (PFS), prostate specific antigen (PSA) reduction ≥ 50% and incidence of grade 3-4 adverse events. The analysis of OS, PFS was done using random effects hazard ratio (HR) by generic inverse variance method and analysis of PSA reduction ≥ 50% and grade 3-4 adverse events was done using random effects risk ratio (RR) by the Mantel-Haenszel method. Results: 12 RCTs comprising 4109 patients were included in the analysis. There was a statistically significant improvement in OS (HR 0.89; 95% CI (0.81, 0.97)) and PFS (HR 0.83; 95% CI (0.76, 0.92)) in the immunotherapy arm compared to placebo or standard treatment arms with moderate quality of evidence. Patients in the immunotherapy group had significant reduction in PSA ≥ 50% (RR 1.71; 95% CI (1.09, 2.68)) but also had statistically significant increased risk of grade 3-4 adverse events (RR (1.25; 95% CI (1.02, 1.54)) when compared to placebo and the standard treatment group. Subgroup analysis showed that the use of vaccine therapy in prostate cancer leads to significant improvement in OS (HR 0.83; 95% CI (0.74, 0.93)) and PFS (HR 0.80; 95% CI (0.67, 0.95)) compared to placebo and standard treatment. The use of immune checkpoint inhibitors was not associated with statistically significant improvement in OS (HR 0.98; 95% CI (0.88, 1.09)) but is associated with improvement in PFS (HR 0.87; 95%CI (0.81, 0.94)). Conclusions: This meta-analysis showed that immunotherapy led to significant improvement in OS, PFS and PSA reduction of ≥ 50%. However, there is an increased incidence of grade 3-4 adverse events with the use of immunotherapy when compared to other standard therapies and placebo. The improvement in overall survival is limited to the use of vaccine therapy and not to immune checkpoint inhibitors. Careful use of selective forms of immunotherapy in mCRPC can lead to greater improvement in survival.

scholarly journals Immune checkpoint inhibitors use and effects on prognosis of COVID-19 infection: a systematic review and meta-analysis

Immunotherapy ◽  
2021 ◽  
Author(s):  
Wenwei Qian ◽  
Ying Ye ◽  
Lugen Zuo ◽  
Ting Song ◽  
Qing Xu ◽  
...  
Keyword(s):  
Systematic Review ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Odds Ratio ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Severe Disease ◽  
Mortality Rates ◽  
Prior Exposure

Aim: We aimed to quantify the effects of immune checkpoint inhibitors (ICIs) on the prognosis of COVID-19. Materials & methods: A meta-analysis was conducted and the hospitalization, severe disease and mortality rates were assessed. Thirteen studies comprising of 4614 cancer patients with COVID-19 were included. Results: When compared with cancer patients without prior ICI exposure, patients with prior ICI treatment exhibited a higher rate of hospitalization (odds ratio [OR] 2.0, 95% CI 1.19–3.38, p = 0.01). However, the OR of severe disease and mortality in ICI exposed cases was similar to non-ICI exposed patients (OR 1.55, 95% CI 0.69–3.51, p = 0.29; OR 1.12, 95% CI 0.85–1.48, p = 0.42, respectively). Conclusion: It is uncertain whether prior exposure to ICIs increases the risk of severe disease and death, however the observed OR suggest a higher rate of hospitalization.

scholarly journals Risk of Pneumonitis Associated With Immune Checkpoint Inhibitors in Melanoma: A Systematic Review and Network Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
You-Meng Sun ◽  
Wei Li ◽  
Zhi-Yu Chen ◽  
Ying Wang
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Randomized Clinical Trials ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Conventional Chemotherapy ◽  
Significant Difference ◽  
Grade 3

BackgroundImmune checkpoint inhibitors (ICIs) have dramatically altered the treatment landscape for patients with melanoma. However, their use also generates unique immune-related adverse effects (irAEs). We performed a systematic review and network meta‐analysis to compare the risk of pneumonitis associated with ICIs for patients with advanced or metastatic melanoma.MethodsPhase II/III randomized clinical trials (RCTs) with ICIs were identified through comprehensive searches of multiple databases. An NMA was conducted to compare the risk of pneumonitis associated with ICIs and all‐grade (grade 1‐5) and high‐grade (grade 3‐5) immune‐related pneumonitis (IRP) were estimated by odds ratios (ORs).ResultsA total of 10 randomized clinical trials involving 5,335 patients were enrolled in this study. Conventional chemotherapy was associated with a lower risk of grade 1–5 IRP compared with ICIs monotherapy (OR, 0.14, 95% CI, 0.03 to 0.73) and dual ICIs combination (OR, 0.03, 95% CI, 0.00 to 0.19). In addition, dual ICIs combination showed a noticeably higher risk than ICI monotherapy (OR, 4.45, 95% CI, 2.14 to 9.25) of grade 1–5 IRP. No significant difference in grade 1–5 IRP was observed between cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) inhibitors. As to grade 3‐5 IRP, no statistically significant difference was found among different ICIs-based regimens.ConclusionThese findings revealed that ICIs could increase the risk of all-grade pneumonitis for patients with advanced melanoma, compared with conventional chemotherapy. Dual ICIs combination could further increase the risk of all-grade pneumonitis than ICIs monotherapy. There was no significant difference in the risk of pneumonia between CTLA-4 and PD-1 inhibitors.

scholarly journals The efficacy and safety of combined immune checkpoint inhibitors (nivolumab plus ipilimumab): a systematic review and meta-analysis

2020 ◽  
Author(s):  
Lihu Gu ◽  
Shengnan Li ◽  
Nannan Du ◽  
Qigu Yao ◽  
Xiaojun Fu ◽  
...  
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Objective Response ◽  
Cochrane Library ◽  
Effect Estimate ◽  
Grade 3 ◽  
Combined Immunotherapy

Abstract Background: Currently, nivolumab and ipilimumab are the most widely used immune checkpoint inhibitors. We performed a meta-analysis to evaluate the efficacy and treatment-related adverse events (TRAEs) of nivolumab-ipilimumab combination therapy in cancer treatment. Methods: We examined data from PubMed, Web of science, EBSCO and Cochrane library. Eleven articles fulfilled our criteria, which we divided into 3 groups; nivolumab and ipilimumab versus ipilimumab, nivolumab and ipilimumab versus ipilimumab and nivolumab 1 mg/kg plus ipilimumab 3 mg/kg (N1I3) versus nivolumab 3 mg/kg plus ipilimumab 1 mg/kg (N3I1). We measured the complete response (CR), partial response (PR), objective response rate (ORR) and TRAEs in any grade and grade 3 or higher. Results: Compared with ipilimumab alone, the combined immunotherapy had better CR (RR: 4.89, p <0.001), PR (RR: 2.75, p <0.001), and ORR (RR: 3.31, p <0.001). The overall effect estimate favored the combined immunotherapy group in terms of the ORR (RR: 1.40, p <0.001) and PR (RR: 1.50, p <0.001) than nivolumab alone. Finally, N1I3 showed better PR (RR: 1.35, p =0.006) and ORR (RR: 1.21, p =0.03) than N3I1. The incidence of any TRAEs was similar between the both groups (RR: 1.05, p =0.06). However, the incidence of serious adverse events (grade 3 or higher) were lower in group N3I1 than group N1I3 (RR: 1.51, p <0.001). Conclusion: This meta-analysis showed that the curative effect of nivolumab plus ipilimumab was better than that of ipilimumab or nivolumab monotherapy. In the combination group, N1I3 combination was more effective than N3I1. Although the side effects were slightly increased in group N1I3, the overall safety was acceptable.

A systematic review and meta-analysis of endocrine-related adverse events associated with immune checkpoint inhibitors

2018 ◽  
Author(s):  
Filette Jeroen de ◽  
Corina Andreescu ◽  
Filip Cools ◽  
Bert Bravenboer ◽  
Brigitte Velkeniers
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Meta Analysis

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).

Cardiotoxicity of immune checkpoint inhibitors: A systematic review and meta-analysis of randomised clinical trials

2021 ◽  
Vol 148 ◽  
pp. 76-91
Author(s):  
Elisa Agostinetto ◽  
Daniel Eiger ◽  
Matteo Lambertini ◽  
Marcello Ceppi ◽  
Marco Bruzzone ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Randomised Clinical Trials
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