A Bayesian Network Meta-Analysis of First-Line Treatments for Non-Small Cell Lung Cancer with High Programmed Death-Ligand 1 Expression

We performed Bayesian network meta-analysis (NMA) to suggest frontline treatments for patients with high PD-L1 expression (at least 50%). A total of 5,237 patients from 22 studies were included in this NMA. In terms of progression-free survival, immune checkpoint inhibitors (ICIs) plus bevacizumab plus chemotherapy had the highest surface under the cumulative ranking curve (SUCRA) value (98.1%), followed by ICI plus chemotherapy (82.9%). In terms of overall survival (OS), dual immunotherapy plus chemotherapy had the highest SUCRA value (79.1%), followed by ICI plus bevacizumab plus chemotherapy (73.4%). However, there was no significant difference of survival outcomes among treatment regimens combined with immunotherapy. Moreover, ICI plus chemotherapy failed to reveal a significant OS superiority to ICI monotherapy (hazard ratio = 0.978, 95% credible internal: 0.771-1.259). In conclusion, this NMA indicates that ICI plus chemotherapy with/without bevacizumab might to be the best options in terms of OS for NSCLC with high PD-L1 expression. Considering there was no significant difference of survival outcomes among treatment regimens incorporating immunotherapy and ICI plus chemotherapy failed to show significant survival benefits over ICI monotherapy, however, ICI monotherapy may be reasonable as first-line treatment for advanced NSCLC with high PD-L1 expression and no targetable aberrations.

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Immune checkpoint inhibitors and chemotherapy in first-line NSCLC: a meta-analysis

Immunotherapy ◽

10.2217/imt-2020-0224 ◽

2021 ◽

Author(s):

Fausto Petrelli ◽

Roberto Ferrara ◽

Diego Signorelli ◽

Antonio Ghidini ◽

Claudia Proto ◽

...

Keyword(s):

Immune Checkpoint ◽

Evaluation System ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Meta Analysis ◽

First Line ◽

Random Effects Models ◽

Assessment Development ◽

Programmed Death ◽

Quantitative Synthesis

This study is a meta-analysis of randomized controlled trials involving first-line studies in which immune checkpoint inhibitors were added to chemotherapy and were compared with chemotherapy alone. The primary end point was overall survival (OS). The analyses used random-effects models and the Grading of Recommendations Assessment, Development, and Evaluation system to rate the quality of the evidence. Nine articles were included for qualitative and quantitative synthesis. A meta-analysis of the nine randomized trials showed a significant benefit in terms of OS (hazard ratio: 0.75 [95% CI: 0.66–0.85]; p < 0.01). Only programmed death ligand-1 positive-high cancers derive a significant OS benefit. In this meta-analysis, there is moderate evidence that the addition of immune checkpoint inhibitors to chemotherapy may improve both OS compared with chemotherapy alone.

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Efficacy and safety of combined androgen blockade with antiandrogen for advanced prostate cancer

Current Oncology ◽

10.3747/co.26.4203 ◽

2019 ◽

Vol 26 (1) ◽

Cited By ~ 1

Author(s):

Y. Yang ◽

R. Chen ◽

T. Sun ◽

L. Zhao ◽

F. Liu ◽

...

Keyword(s):

Prostate Cancer ◽

Meta Analysis ◽

Progression Free Survival ◽

Efficacy And Safety ◽

First Line ◽

Combined Androgen Blockade ◽

Hazard Ratios ◽

Significant Difference ◽

Grade 3 ◽

Androgen Blockade

Background Combined androgen blockade (cab) is a promising treatment modality for prostate cancer (pca). In the present meta-analysis, we compared the efficacy and safety of first-line cab using an antiandrogen (aa) with castration monotherapy in patients with advanced pca.Methods PubMed, embase, Cochrane, and Google Scholar were searched for randomized controlled trials (rcts) published through 12 December 2016. Hazard ratios (hrs) with 95% confidence intervals (cis) were determined for primary outcomes: overall survival (os) and progression-free survival (pfs). Subgroup analyses were performed for Western compared with Eastern patients and use of a nonsteroidal aa (nsaa) compared with a steroidal aa (saa).Results Compared with castration monotherapy, cab using an aa was associated with significantly improved os (n = 14; hr: 0.90; 95% ci: 0.84 to 0.97; p = 0.003) and pfs (n = 13; hr: 0.89; 95% ci: 0.80 to 1.00; p = 0.04). No significant difference in os (p = 0.71) and pfs (p = 0.49) was observed between the Western and Eastern patients. Compared with castration monotherapy, cab using a nsaa was associated with significantly improved os (hr: 0.88; 95% ci: 0.82 to 0.95; p = 0.0009) and pfs (hr: 0.85; 95% ci: 0.73 to 0.98; p = 0.007)—a result that was not achieved with cab using a saa. The safety profiles of cab and monotherapy were similar in terms of adverse events, including hot flushes, impotence, and grade 3 or 4 events, with the exception of risk of diarrhea and liver dysfunction or elevation in liver enzymes, which were statistically greater with cab using an aa.Conclusions Compared with castration monotherapy, first-line cab therapy with an aa, especially a nsaa, resulted in significantly improved os and pfs, and had an acceptable safety profile in patients with advanced pca.

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Differential Dermatologic Adverse Events Associated With Checkpoint Inhibitor Monotherapy and Combination Therapy: A Meta-Analysis of Randomized Control Trials

Frontiers in Pharmacology ◽

10.3389/fphar.2021.640099 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yang Ge ◽

Huiyun Zhang ◽

Nathaniel Weygant ◽

Jiannan Yao

Keyword(s):

Relative Risk ◽

Combination Therapy ◽

Adverse Events ◽

Checkpoint Inhibitors ◽

Meta Analysis ◽

High Grade ◽

Treatment Regimens ◽

Increased Risk ◽

Significant Difference ◽

Dermatologic Adverse Events

Background: As immune checkpoint inhibitors (ICIs) transition to the forefront of cancer treatment, a better understanding of immune related adverse events (IRAEs) is essential to promote safe clinical practice. Dermatologic adverse events are the most common IRAEs and can lead to drug withdrawal and decreased quality of life. This meta-analysis aimed to investigate the risk of the most prevalent dermatologic adverse events (pruritus and rash) among various ICI treatment regimens.Methods: A systematic search of electronic databases was performed to identify qualified randomized controlled trials (RCTs). Data for any grade and high grade pruritus and rash were extracted for meta-analysis. Two reviewers independently assessed methodological quality. The relative risk summary and 95% confidence interval were calculated.Results: 50 RCTs involving 29941 patients were analyzed. The risk of pruritus (2.15 and 4.21 relative risk respectively) and rash (1.61 and 3.89 relative risk respectively) developing from CTLA-4 or PD-1/-L1 inhibitor were increased compared to placebo, but this effect was not dose-dependent. PD-1/-L1 plus CTLA-4 inhibitor was associated with increased risk of pruritus (1.76 and 0.98 relative risk respectively) and rash (1.72 and 1.37 relative risk respectively) compared to either monotherapy. Compared with CTLA-4 inhibitor, PD-1/-L1 inhibitor had a significantly decreased risk of pruritus and rash in both monotherapy and combination therapy (0.65 and 0.29 relative risk respectively). No significant difference was found between PD-1/-L1 inhibitor combined with chemotherapy and PD-1/-L1 monotherapy in any grade and high grade rash (0.84 and 1.43 relative risk respectively). In subgroup analyses, PD-1 inhibitor was associated with reduced risk of pruritus and rash compared to PD-L1 inhibitor.Conclusion: Our meta-analysis demonstrates a better safety profile for PD-1/-L1 inhibitor compared to CTLA-4 inhibitor in terms of pruritus and rash among both monotherapy and multiple combination therapies. PD-L1 inhibitor may contribute to an increased risk of pruritus and rash compared to PD-1 inhibitor.

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The real-word evidence of first-line treatment of pembrolizumab in advanced NSCLC.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e18731 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e18731-e18731

Author(s):

Pin Li ◽

Shirish M. Gadgeel ◽

Laila Poisson

Keyword(s):

Clinical Trials ◽

Real World ◽

Survival Probability ◽

Advanced Nsclc ◽

Meta Analysis ◽

Stage Iv ◽

Progression Free Survival ◽

First Line ◽

Real World Data ◽

Significant Difference

e18731 Background: For advanced non-small cell lung cancer (NSCLC), evidence from clinical trials indicates the superiority of pembrolizumab (P) than chemotherapy (C) in PD-L1 positive patients and superiority of P+C than C among PD-L1 unselected patients. Meta-analysis from different clinical trials stated P+C failed to improve overall survival (OS) or progression-free survival (PFS) compared with P alone. This study used real-world data of PD-L1+ patients with advanced NSCLC to compare treatment effect of P with P+C. Methods: A retrospective analysis of adult patients diagnosed between 2015-2020 with stage IV NSCLC with PD-L1+ and without EGFR/ALK mutation was examined using de-identified Syapse Learning Health Network(LHN). We compared the patients with first-line (1L) treatment of pembrolizumab + carboplatin + chemo (P+C) and patients with 1L treatment of P only (P). Patient characteristics and survival outcomes including real-world OS (rwOS) and real-world time to next treatment (rwTTNT) were collected. Results: 485 patients were included: 231 on P+C and 254 on P. The two groups are similar in race, primary tumor histology and ECOG, and P are older in age and have more female. The median rwOS for P+C is longer than P (13.2 vs 11.0 month), 1 year survival probability is higher (55% vs 49%), but 2 year survival probability is lower (34% vs 39%). Coxph model shows no significant difference between two groups (HR=0.89, 95% CI 0.69-1.14, p=0.34). Subgroup analysis of patients age≥75 shows median rwOS for P+C is shorter than P (8.7 vs 13.2 month), 1 year survival probability is lower (46% vs 51%). Coxph model shows no significant difference between two groups (HR=1.32, 95% CI 0.81-2.16, p=0.27). In each treatment group, the median rwOS for female is longer than male (13.2 vs 7.9 month in P, 15.8 vs 12.2 month in P+C), and 1 year survival probability is higher (52% vs 45% in P, 59% vs 53% in P+C). Coxph model shows no significant difference between female and male (HR=0.81, 95% CI 0.58-1.15, p=0.23 in P; HR=0.90, 95% CI 0.62-1.30, p=0.57 in P+C). Conclusions: Among patients with PD-L1+ advanced NSCLC, there is no significant difference in rwOS for patients with 1L treatment of P+C or P alone.[Table: see text]

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Efficacy of Abiraterone and Enzalutamide in Pre- and Postdocetaxel Castration-Resistant Prostate Cancer: A Trial-Level Meta-Analysis

Prostate Cancer ◽

10.1155/2017/8560827 ◽

2017 ◽

Vol 2017 ◽

pp. 1-8 ◽

Cited By ~ 6

Author(s):

Mike Fang ◽

Mary Nakazawa ◽

Emmanuel S. Antonarakis ◽

Chun Li

Keyword(s):

Prostate Cancer ◽

Median Overall Survival ◽

Meta Analysis ◽

Progression Free Survival ◽

Castration Resistant Prostate Cancer ◽

First Line ◽

Free Survival ◽

Castration Resistant ◽

Significant Difference ◽

Method Approach

We examined the comparative efficacies of first-line abiraterone and enzalutamide in pre- and postdocetaxel settings in castration-resistant prostate cancer (CRPC) through a trial level meta-analysis. A mixed method approach was applied to 19 unique studies containing 17 median overall survival (OS) estimates and 13 median radiographic progression-free survival (PFS) estimates. We employed a random-effects meta-analysis to compare efficacies of abiraterone and enzalutamide with respect to OS and PFS. In the predocetaxel setting, enzalutamide use was associated with an increase in median OS of 5.9 months (p<0.001), hazard ratio (HR) = 0.81, and an increase in median PFS of 8.3 months (p<0.001), HR = 0.47 compared to abiraterone. The advantage of enzalutamide improved after adjusting for baseline Gleason score to 19.5 months (p<0.001) and 14.6 months (p<0.001) in median OS and PFS, respectively. In the postdocetaxel setting, the advantage of enzalutamide use was nominally significant for median PFS (1.2 months p=0.02 without adjustment and 2.2 months and p=0.0007 after adjustment); there was no significant difference in median OS between the two agents. The results from this comprehensive meta-analysis suggest a survival advantage with the use of first-line enzalutamide over abiraterone in CRPC and highlight the need for prospective clinical trials.

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

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835919861905 ◽

2019 ◽

Vol 11 ◽

pp. 175883591986190 ◽

Cited By ~ 9

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.

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Optimal Therapies for Recurrent Glioblastoma: A Bayesian Network Meta-Analysis

Frontiers in Oncology ◽

10.3389/fonc.2021.641878 ◽

2021 ◽

Vol 11 ◽

Author(s):

Wenlin Chen ◽

Yuekun Wang ◽

Binghao Zhao ◽

Penghao Liu ◽

Lei Liu ◽

...

Keyword(s):

Cluster Analysis ◽

Bayesian Network ◽

Active Drug ◽

Meta Analysis ◽

Objective Response ◽

Progression Free Survival ◽

Recurrent Glioblastoma ◽

Advanced Therapy ◽

Significant Difference ◽

And Cluster Analysis

The optimal treatment of recurrent glioblastoma (GBM) remains controversial. Therefore, our study aimed to compare and rank active therapies in recurrent GBM. We performed a systematic review and a Bayesian network meta-analysis. We obtained a treatment hierarchy using the surface under the cumulative ranking curve and mean ranks. A cluster analysis was conducted to aggregate the separated results of three outcomes. The protocol was registered in PROSPERO (CRD42019146794). A total of 1,667 citations were identified, and 15 eligible articles with 17 treatments remained in the final network meta-analysis. Pairwise comparison showed no significant difference on the 6-month progression-free survival (6-m PFS) rate, objective response rate (ORR), and overall survival (OS). Among the reports, cediranib plus lomustine (CCNU) corresponded to the highest rates of grade 3-4 adverse events. Ranking and cluster analysis indicated that bevacizumab (BEV) plus CCNU and regorafenib had a higher efficacy on the ORR, 6-m PFS rate and OS, and that BEV monotherapy or BEV combined with active drug therapies was advantageous for the ORR and 6-m PFS rate. Additionally, tumor treatment fields (TTF) plus BEV showed a relatively higher SUCRA value in OS. According to ranking and cluster analysis, BEV plus CCNU and regorafenib are the primary recommendations for treatment. BEV monotherapy alone or combined with active drug therapies are recommended in patients with severe neurological symptoms. Advanced therapy, such as TTF and immunotherapy, remain to be investigated in future studies.

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Comparison of the survival outcomes of laparoscopy versus laparotomy in treatment of early-stage ovarian cancer: a systematic review and meta-analysis

Journal of Ovarian Research ◽

10.1186/s13048-021-00793-1 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Qingduo Kong ◽

Hongyi Wei ◽

Jing Zhang ◽

Yilin Li ◽

Yongjun Wang

Keyword(s):

Ovarian Cancer ◽

Overall Survival ◽

Early Stage ◽

Meta Analysis ◽

Progression Free Survival ◽

Cochrane Library ◽

Survival Outcomes ◽

Free Survival ◽

Review Manager ◽

Early Stage Ovarian Cancer

Abstract Background Laparoscopy has been widely used for patients with early-stage epithelial ovarian cancer (eEOC). However, there is limited evidence regarding whether survival outcomes of laparoscopy are equivalent to those of laparotomy among patients with eEOC. The result of survival outcomes of laparoscopy is still controversial. The aim of this meta-analysis is to analyze the survival outcomes of laparoscopy versus laparotomy in the treatment of eEOC. Methods According to the keywords, Pubmed, Embase, Cochrane Library and Clinicaltrials.gov were searched for studies from January 1994 to January 2021. Studies comparing the efficacy and safety of laparoscopy versus laparotomy for patients with eEOC were assessed for eligibility. Only studies including outcomes of overall survival (OS) were enrolled. The meta-analysis was performed using Stata software (Version 12.0) and Review Manager (Version 5.2). Results A total of 6 retrospective non-random studies were included in this meta-analysis. The pooled results indicated that there was no difference between two approaches for patients with eEOC in OS (HR = 0.6, P = 0.446), progression-free survival (PFS) (HR = 0.6, P = 0.137) and upstaging rate (OR = 1.18, P = 0.54). But the recurrence rate of laparoscopic surgery was lower than that of laparotomic surgery (OR = 0.48, P = 0.008). Conclusions Laparoscopy and laparotomy appear to provide comparable overall survival and progression-free survival outcomes for patients with eEOC. Further high-quality studies are needed to enhance this statement.

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PD-L1 Targeting Immune-Microbubble Complex Enhances Therapeutic Index in Murine Colon Cancer Models

Pharmaceuticals ◽

10.3390/ph14010006 ◽

2020 ◽

Vol 14 (1) ◽

pp. 6

Author(s):

Daehyun Kim ◽

Seung Soo Lee ◽

Hyungwon Moon ◽

So Yeon Park ◽

Hak Jong Lee

Keyword(s):

Cancer Immunotherapy ◽

Focused Ultrasound ◽

Therapeutic Potential ◽

Checkpoint Inhibitors ◽

Therapeutic Index ◽

Treatment Regimens ◽

Cancer Models ◽

Programmed Death ◽

Murine Colon ◽

Cell Death Protein

Cancer immunotherapy has revolutionized the way different neoplasms are treated. Among the different variations of cancer immunotherapy, the checkpoint inhibitors targeting the programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) axis have been validated and are currently used in the clinics. Nevertheless, these therapeutic antibodies are associated with significant side effects and are known to induce immune-related toxicities. To address these issues, we have developed an immune-microbubble complex (IMC) which not only reduces the toxicities associated with the antibodies but also enhances the therapeutic efficacy when combined with focused ultrasound. The concept of IMCs could be applied to any type of antibody-based treatment regimens to maximize their therapeutic potential.

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