Efficacy and Safety of Immune Checkpoint Inhibitors for Advanced Malignant Melanoma: A Meta-Analysis on Monotherapy Vs Combination Therapy

被引:6
作者
Pradeep, Jnaneshwari [1 ]
Win, Thin Thin [2 ]
Aye, Saint Nway [2 ]
Sreeramareddy, Chandrashekhar T. [3 ]
机构
[1] Int Med Univ, Sch Med, 126 Jalan Jalil Perkasa 19,Bukit Jalil, Kuala Lumpur 57000, Malaysia
[2] Int Med Univ, Sch Med, Pathol Dept, 126,Jalan Jalil Perkasa 19,Bukit Jalil, Kuala Lumpur 57000, Malaysia
[3] Int Med Univ, Sch Med, Community Med Dept, 126,Jalan Jalil Perkasa 19,Bukit Jalil, Kuala Lumpur 57000, Malaysia
关键词
Immune checkpoint inhibitors; advanced malignant melanoma; systematic review; meta; -analysis; monotherapy; combination therapy; COMBINED NIVOLUMAB; IPILIMUMAB; SURVIVAL; BLOCKADE; CANCER; PEMBROLIZUMAB; CHEMOTHERAPY;
D O I
10.7150/jca.72210
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Immune checkpoint inhibitors (ICIs) are approved as cancer immunotherapeutic agents for advanced malignant melanoma (MM) in recent years, and nivolumab and ipilimumab are the most widely used ICIs either alone or in combination. However, their efficacy and safety between single and combined ICIs are not clear. This meta-analysis (MA) is aimed to update the efficacy and safety of ICIs by comparing monotherapy and combination therapy in the treatment of advanced MM.Method: We searched PubMed, Embase, EbscoHost and ClinicalTrials.gov for the eligible randomized controlled trials (RCTs) which compared the efficacy and safety of ICIs between a single ICI and combined ICIs. The outcomes analyzed included overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and treatment-related adverse events (AEs). A fixed-effect or random-effects model was adopted depending on the study heterogeneity.Results: A total of nine RCTs were included in this MA. Regarding the efficacy, combined nivolumab and ipilimumab therapy showed statistically significant prolonged OS and PFS with HR 0.65, 95% CI [0.53, 0.79], p <0.0001 and HR 0.48, 95% CI [0.38, 0.60], p<0.0001 respectively. Combination therapy with nivolumab and ipilimumab also showed statistically significant longer ORR than monotherapy; with RR 2.15, 95% CI [1.63, 2.84], p <0.00001. In terms of safety, the incidence of all AEs which include any AEs, high-grade, haematological, gastrointestinal, dermatological, pulmonary, liver and endocrine AEs were significantly lower with monotherapy (either nivolumab or ipilimumab) of ICI compared to combination ICI therapy with a p-value <0.00001 to 0.03.Conclusion: Efficacy of the combined nivolumab and ipilimumab was better than a single ICI, especially in the treatment of advanced MM. Although combination therapy showed better efficacy than monotherapy, monotherapy (either nivolumab or ipilimumab) was safer than combination therapy as it tended to decrease the incidence of most of the treatment-related AEs.
引用
收藏
页码:3091 / 3102
页数:12
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