scholarly journals The association between immune-related adverse events and the prognosis of solid cancer patients treated with immunotherapy: a systematic review and meta-analysis

2020 ◽  
Vol 12 ◽  
pp. 175883592098054
Author(s):  
Huilin Xu ◽  
Ximing Xu ◽  
Wei Ge ◽  
Jinju Lei ◽  
Dedong Cao

Background: Immune-related adverse events (irAEs) are common during immune checkpoint inhibitor (ICI) treatment and reported to be associated with good survival. This study evaluated the association between onset timing of irAEs and survival of cancer patients treated with ICIs. Methods: Databases including PubMed, Embase, and the Cochrane library were systematically searched to retrieve clinical studies assessing the relationship between irAEs and survival in cancer patients with ICIs. The overall response rate for treatment response and hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS) were calculated using RevMan 5.3. Subgroup analysis in terms of cancer type, ICIs type, region, specific irAEs, accordingly. Results: A total of 34 studies were included. The HRs for OS and PFS in cancer patients with versus without irAEs were 0.57 [95% confidence interval (CI): 0.44, 0.74; p < 0.0001], and 0.50 (95% CI: 0.37, 0.67; p < 0.00001), respectively. The odds ratio for overall response in cancer patients with irAEs was 4.72 (95% CI: 3.48, 6.40; p < 0.00001) compared with those without irAEs. Subgroup analyses suggested that the prognostic role of irAEs was associated with cancer types and region, but not irAEs types. The landmark analysis of OS revealed that there is a non-proportional (early) effect of irAEs on OS in ICI-treated cancer patients (landmark >12 weeks, HROS = 1.08; 95% CI: 0.89, 1.30; p = 0.46). Conclusion: Our findings suggest that the occurrence of irAEs could be a prognostic factor for cancer patients who were treated with ICIs.

2021 ◽  
Vol 17 ◽  
Author(s):  
Vinod Solipuram ◽  
Harish Gopalakrishna ◽  
Gayatri Naira ◽  
Akhila Mohan

Introduction: Pancreatic cancer is an aggressive tumor that had an estimated 57,600 new cases and 47,050 deaths in 2020 in the US alone. Recent studies have targeted tumor microenvironment (TME) for better delivery of systemic chemotherapy like PEGPH20, which degrades hyaluronic acid in the extracellular matrix (ECM). A meta-analysis of these Randomized controlled trials (RCTs) to test the efficacy of PEGPH20 was performed. Methods: A systematic search was performed using PubMed, Embase, and Cochrane library without language limitations from inception to July 30, 2020. A total of 59 articles was identified, and 3 RCTs were included in the final analysis. The primary outcome was progression-free survival (PFS), and secondary outcomes were overall survival (OS), deaths from adverse events, thromboembolic events, serious adverse events (SAE), and febrile neutropenia. Results: There was no statistically significant improvement in PFS (HR= 0.94; 95%CI (0.79, 1.11)) in the PEGPH20 group when compared to the standard treatment/placebo group. There was no significant difference among OS (HR= 0.99, 95%CI (0.83, 1.17), deaths from adverse events (RR=0.97; 95%CI (0.54, 1.73)), thromboembolic events (RR= 1.49; 95%CI (0.92, 2.44)), and febrile neutropenia (RR= 0.88; 95%CI (0.45, 1.72), however, there was statistically significant increase in SAE (RR = 1.59; 95%CI (1.01, 2.52) in the PEGPH20 group compared to the placebo group. Conclusion: This meta-analysis showed that PEGPH20 did not improve the PFS or OS. Moreover, there is an increased incidence of serious adverse events with the use of PEGPH20 compared to standard therapies.


2020 ◽  
Vol 9 (5) ◽  
pp. 1458 ◽  
Author(s):  
Fausto Petrelli ◽  
Alessandro Iaculli ◽  
Diego Signorelli ◽  
Antonio Ghidini ◽  
Lorenzo Dottorini ◽  
...  

Antibiotics (ABs) are common medications used for treating infections. In cancer patients treated with immune checkpoint inhibitors (ICIs), concomitant exposure to ABs may impair the efficacy of ICIs and lead to a poorer outcome compared to AB non-users. We report here the results of a meta-analysis evaluating the effects of ABs on the outcome of patients with solid tumours treated with ICIs. PubMed, the Cochrane Library and Embase were searched from inception until September 2019 for observational or prospective studies reporting the prognoses of adult patients with cancer treated with ICIs and with or without ABs. Overall survival (OS) was the primary endpoint, and progression-free survival (PFS) was the secondary endpoint. The effect size was reported as hazard ratios (HRs) with a 95% confidence interval (CI) and an HR > 1 associated with a worse outcome in ABs users compared to AB non-users. Fifteen publications were retrieved for a total of 2363 patients. In the main analysis (n = 15 studies reporting data), OS was reduced in patients exposed to ABs before or during treatment with ICIs (HR = 2.07, 95%CI 1.51–2.84; p < 0.01). Similarly, PFS was inferior in AB users in n = 13 studies with data available (HR = 1.53, 95%CI 1.22–1.93; p < 0.01). In cancer patients treated with ICIs, AB use significantly reduced OS and PFS. Short duration/course of ABs may be considered in clinical situations in which they are strictly needed.


2021 ◽  
Vol 10 ◽  
Author(s):  
Xiaojie Xia ◽  
Zeyuan Liu ◽  
Qin Qin ◽  
Xiaoke Di ◽  
Zhaoyue Zhang ◽  
...  

BackgroundConcurrent chemoradiotherapy (CCRT) is the standard treatment for nonsurgical esophageal cancer (EC). However, esophageal cancer patients receiving CCRT alone are still unsatisfactory in terms of local control and overall survival (OS) benefit. Clinicians generally add consolidation chemotherapy (CCT) after CCRT. It remains controversial whether CCT following CCRT is beneficial for esophageal cancer. We, therefore, undertook a meta-analysis to assess the need for CCT in inoperable esophageal cancer.Materials and MethodsWe combed PubMed, Embase, Cochrane Library, Web of Science, and CNKI for relevant published articles up to July 2020 that compared CCRT plus CCT to CCRT alone for patients with nonsurgical EC. Our primary endpoint was OS and progression-free survival (PFS), and the secondary endpoint was treatment toxicity. We analyzed the hazard ratio (HR) to estimate the time-to-event data and the odds ratio (OR) to compare the treatment-related effect. To assess heterogeneity, we performed the I2 test and examined publication bias using funnel plots analysis.ResultsThe 11 retrospective studies involved 2008 patients. Of these 2008 patients, 1018 received CCRT plus CCT, and 990 received CCRT. Compared to CCRT alone, CCT after CCRT did not improve disease control rate (DCR) (OR 1.66; 95% CI 0.53–5.15, p=0.384) and objective response rate (ORR) (OR 1.44; 95% CI 0.62–3.35, p=0.393). However, OS (HR 0.72; 95% CI 0.59–0.86, p &lt; 0.001) and PFS (HR 0.61; 95% CI 0.44–0.84, p=0.003) did increase. Our results show that CCT plus CCRT had a clear survival advantage over CCRT alone. The risk of treatment toxicity did not increase for EC patients who received CCT.ConclusionCCT after CCRT significantly increases OS and PFS in patients with nonsurgical EC and could provide them remarkable survival benefits. The results provide an evidence-based framework for the use of CCT after CCRT.


2019 ◽  
Author(s):  
Kaiping Zhang ◽  
Zhi Sun ◽  
Yin Zhang ◽  
Chaozhao Liang ◽  
Li Zhang ◽  
...  

Abstract Background It is well known that liposome-based delivery of cytotoxic chemotherapeutics has been proposed as a putative strategy to enhance drug tolerability and efficacy compared to the conventional chemotherapy. However, its potential effects on improving cancer patients prognosis remain largely unknown. The current meta-analysis is to explore the prognosis of cancer patients undergoing liposomal doxorubicin-based chemotherapy. Methods A detailed review of English and Chinese literature was conducted from PubMed, Embase, Cochrane Library, China Biology Medicine disc (CBM), China National Knowledge Infrastructure (CNKI) up to March 21st, 2019. We evaluate its possible correlations using hazard ratios (HRs) with 95% confidence intervals (CIs). The pooled data were calculated by STATA software and Review Manager 5.3 software. Results Consequently, 26 studies including 7943 patients were satisfied in current analysis. We found that there were no significant differences between liposomal and conventional chemotherapy in OS (HR=0.98, 95%CI: 0.93-1.04, P=0.544) and PFS (HR=1.00, 95%CI: 0.92-1.10, P=0.945). Likewise, subgroup-analysis regarding country, cancer type and sample sizes also showed the similar results of the two paired groups. Conclusion Taken together, our findings have demonstrated that there was no association of undergoing liposomal doxorubicin-based chemotherapy with cancer prognosis. However, detailed and further studies are needed to confirm these conclusions.


Author(s):  
Fausto Petrelli ◽  
Alessandro Iaculli ◽  
Diego Signorelli ◽  
Antonio Ghidini ◽  
Lorenzo Dottorini ◽  
...  

Antibiotics (ABs) are common medications used for treating infections. In cancer patients treated with immune checkpoint inhibitors (ICIs), concomitant exposure to ABs may impair the efficacy of ICIs and lead to a poorer outcome compared to AB non-users. We report here the results of a meta-analysis evaluating the effects of ABs on the outcome of patients with solid tumors treated with ICIs. PubMed, the Cochrane Library, and Embase were searched from inception until September 2019 for observational or prospective studies reporting prognosis of adult patients with cancer treated with ICIs and with or without ABs. Overall survival (OS) was the primary endpoint, and progression-free survival (PFS) was the secondary endpoint. The effect size was reported as hazard ratios (HRs) with a 95% confidence interval (CI), and an HR &gt; 1 associated with a worse outcome in ABs users compared to no-ABs users. Fifteen publications were retrieved for a total of 2363 patients. In the main analysis (n = 15 studies reporting data), OS was reduced in patients exposed to ABs before or during treatment with ICIs (HR = 2.07, 95%CI 1.51&ndash;2.84; P&lt;.01). Similarly, PFS was inferior in ABs users in n = 13 studies with data available (HR = 1.53, 95%CI 1.22&ndash;1.93; p&lt;.01). In cancer patients treated with ICIs, AB use significantly reduces OS and PFS. Short duration/course of ABs may be considered in clinical situations in which they are strictly needed.


2018 ◽  
Vol 2018 ◽  
pp. 1-16 ◽  
Author(s):  
Wen Liu ◽  
Kaiping Zhang ◽  
Pengfei Wei ◽  
Yue Hu ◽  
Yaqin Peng ◽  
...  

The correlation between miR-200 family overexpression and cancer prognosis remains controversial. Therefore, we conducted a systematic review and meta-analysis by searching PubMed, Embase, Cochrane Library, China Biology Medicine disc (CBM), and China National Knowledge Infrastructure (CNKI) to identify eligible studies. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to evaluate the strength of the correlations. Additionally, different subgroup analyses and publication bias test were performed. Eventually, we analyzed 23 articles that included five tumor types and 3038 patients. Consequently, high expression of miR-200 family in various tumors was associated with unfavorable overall survival (OS) in both univariate (HR=1.32, 95% CI: 1.14–1.54, P<0.001) and multivariate (HR=1.32, 95% CI: 1.16–1.49, P<0.001) analyses. Likewise, a similar result was found in different subgroups of the patient source, cancer type, test method, sample source, miR-200 component, and sample size. However, no association of miR-200 family was detected with recurrence- or relapse-free survival (RFS) (univariate: HR=1.02, 95% CI: 0.96–1.09, P=0.47; multivariate: HR=1.07, 95% CI: 1.00–1.14, P=0.07), progression-free survival (PFS) (univariate: HR=0.96, 95% CI: 0.54–1.70, P=0.88; multivariate: HR=1.17, 95% CI: 0.86–1.61, P=0.32), and disease-free survival (DFS) (univariate: HR=0.90, 95% CI: 0.74–1.09, P=0.29; multivariate: HR=0.98, 95% CI: 0.68–1.41, P=0.90). Our findings have provided convincing evidence that miR-200 family overexpression suggested poor prognosis of various cancer types, which efforts may raise the potential use of miR-200 family for cancer prognosis in clinical practice.


2021 ◽  
Vol 20 ◽  
pp. 153303382098308
Author(s):  
Jing Jin ◽  
Lan Yang ◽  
Dan Liu ◽  
Wei Min Li

Background: The overall prognosis of lung cancer remains unfavorable and novel prognostic biomarkers of lung cancer are needed warranted. Accumulating evidence indicate that systemic inflammation plays a vital role in lung cancer. The lymphocyte-to-monocyte ratio (LMR) is biomarker that reflects the level of systemic inflammation. Objective: To perform a comprehensive meta-analysis exploring the correlation of pretreatment LMR with the overall survival (OS) and progression-free survival (PFS) of lung cancer patients. Methods: We conducted searches of the PubMed, Embase, Cochrane Library, and Web of Science databases to May 2020 to identify relevant studies and calculated combined hazard ratios (HRs) to evaluate the association between pretreatment LMR and survival time in patients with lung cancer. Results: A total of 23 studies comprising 8361 lung cancer patients were included. Among the patients, 5702 (68%) were males, 4548 were current smokers and 2212 were diagnosed with squamous carcinoma. The pooled analysis revealed that decreased pretreatment LMR was significantly correlated with reduced of PFS (HR = 1.49, 95% CI: 1.34-1.67, p < 0.01) and reduced OS (HR = 1.61, 95% CI: 1.45-1.79, p < 0.01) among lung cancer patients. Furthermore, in the subgroup analyses according to histologic type, a lower level of pretreatment LMR seemed to be unrelated to the poorer OS of small cell lung cancer (SCLC) patients (HR = 1.21, 95%CI: 0.87-1.67, P = 0.25). Conclusions: Decreased pretreatment LMR in peripheral blood was associated with shorter OS and PFS in lung cancer patients, suggesting its potential prognostic value.


Author(s):  
Elisa Gobbini ◽  
Julie Charles ◽  
Anne-Claire Toffart ◽  
Marie-Thérèse Leccia ◽  
Denis Moro-Sibilot ◽  
...  

Abstract Background Immune checkpoint inhibitor (ICPis) re-challenge could be an attractive therapeutic option considering its good safety profile. However, little data is available regarding anti-PD-1/anti-PD-L1 retreatment. We conducted a meta-analysis focusing on outcomes of solid cancer patients performing this strategy. Methods Fourteen full papers involving 74 patients were included. Individual data about best response or progression-free survival (PFS) upon the first and second course of anti-PD-1/ anti-PD-L1 were collected. Results Non-small-cell lung cancer (53%) and melanoma (34%) were the most represented cancers. Higher objective response (46% versus 24%, p = 4.10 -4 ) and disease control rates (73% versus 52%, p = 7.10 -3 ) were obtained upon the first ICPi course compared to re-challenge. No association between responses obtained with the two ICPis courses was found ( p = 3.10 -1 ). The PFS upon the first ICPi (PFS1) was longer than that after re-challenge (PFSR) (6.6 versus 2.8 months, hazard ratio (HR) 0.57, p = 2.10 -3 ). A longer PFSR was obtained in patients with a longer PFS1 ( p = 6.10 -3 ), in those who discontinued the first ICPi due to toxicity or per protocol (8.8 versus 2.1 months if disease progression occurs, p = 2.10 -3 ), and in those not receiving intercalated treatment between the two ICPis (6.6 versus 2.1 months for the treated ones, p = 1.10 -3 ). Conclusion Anti-PD-1/anti-PD-L1 re-challenge showed interesting clinical activity in selected patients, mainly in those achieving a long-term response upon the first ICPi course, that do not discontinue therapy because of disease progression, or that are able to keep a treatment-free period.


2021 ◽  
Vol 11 ◽  
Author(s):  
Hui Liu ◽  
Xiao-Li Yang ◽  
Xiao-Yun Yang ◽  
Zhao-Ru Dong ◽  
Zhi-Qiang Chen ◽  
...  

BackgroundThe lung immune prognostic index (LIPI) is recently developed to predict immune checkpoint inhibitors (ICIs) treatment outcomes for non-small cell lung cancer. However, its predictive value for other types of cancer remained unclear. This meta-analysis aimed to evaluate the association between pretreatment LIPI score and therapeutic outcomes in cancer patients treated with ICIs.MethodsWe searched PubMed, Cochrane Library literature databases and EMBASE for abstracts and full-text articles published from the inception of the database until 16th, Nov 2020. Meta-analyses were performed separately for progression-free survival (PFS) and overall survival (OS) by using the random-effects model.ResultsA total of 12 studies involving 4883 patients receiving ICIs treatment were identified for the primary analysis. The pooled results implied that compared with good LIPI score groups, patients with poor or intermediate LIPI score were significantly associated with worse OS (HR=3.33, 95%CI 2.64-4.21, P &lt; 0.001, I2 = 64.2%; HR=1.71, 95%CI 1.43-2.04, P &lt; 0.001, I2 = 43.6%, respectively) and PFS (HR=2.73,95%CI 2.00-3.73, P &lt; 0.001, I2 = 78.2%; HR=1.43, 95%CI 1.28-1.61, P &lt; 0.001, I2 = 16.3%, respectively). Also, for 1873 patients receiving chemotherapy, a poor LIPI score was significantly associated with worse OS (HR=2.30, 95%CI 1.73-3.07, P &lt; 0.001; I2 = 56.2%) and PFS (HR=1.92,95%CI 1.69-2.17; P &lt; 0.001; I2 = 0.0%) compared with good LIPI score groups.ConclusionsA good LIPI score was significantly correlated with improved OS and PFS in cancer patients receiving ICIs or chemotherapy, regardless of the types of cancer.


2021 ◽  
Author(s):  
Cheng-Jiang Liu ◽  
Ting Hu ◽  
Ping Shao ◽  
Wu-Yang Chu ◽  
Yu Cao ◽  
...  

Abstract Objective To evaluate the effectiveness and safety of TAS-102 in the treatment of metastatic colorectal cancer. Methods The pubmed, web of science, medline, cochrane library databases were searched for the literature on TAS-102 treatment of metastatic colorectal cancer. Extract data such as median Overall Survival (mOS), median Progression-Free Survival (mPFS) and the incidence of adverse events for meta-analysis. Results Our study found that the mOS of patients treated with TAS-102 was 7.74 (95%CI: 6.09–9.85) and the mPFS was 2.91 (95%CI: 2.38–3.57). The mOS in patients treated by TAS-102 Combined with bevacizumab is 10.41 (95%CI: 8.40-12.89) and the mPFS is 4.35 (95%CI: 3.05–6.20). In the control experiment, the patients' mOS and mPFS were improved. TAS-102 + B VS. TAS- 102 (OR = 0.41, 95% CI: 0.18–0.93; OR = 0.72, 95% CI: 0.63–0.83). TAS-102 VS. Placebo(OR = 0.44, 95% CI: 0.29–0.67; OR = 0.51, 95% CI: 0.42–0.62). The incidence of adverse events in combination with bevacizumab will increase. Conclusion TAS-102 single or combined treatment can significantly improve the survival of patients, and drug safety should be considered when formulating a combined treatment plan.


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