Dataset Information

Efficacy and Safety of PD-1/PD-L1 Checkpoint Inhibitors versus Anti-PD-1/PD-L1 Combined with Other Therapies for Tumors: A Systematic Review.

ABSTRACT:

Objective

In recent years, the anti-programmed cell death protein-1 and its ligand (PD-1/PD-L1) or combination therapies have been recommended as an alternative emerging choice of treatment for oncology patients. However, the efficacy and adverse events of different combination strategies for the treatment of tumors remain controversial.

Methods

PubMed, Embase, Cochrane Library, the American Society of Clinical Oncology (ASCO), and the European Society of Medicine Oncology (ESMO) were searched from database inception until 16 February 2022. The endpoints of objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were analyzed from different treatment schemes and tumor types. The protocol was registered in PROSPERO (CRD42022328927).

Results

This meta-analysis included forty-eight eligible studies. Combination therapy has improved ORR (RR = 1.40, p < 0.001), DCR (RR = 1.22, p < 0.001), and PFS (the median survival ratio (MSR) was estimated to be 1.475 p < 0.001) compared to anti-PD-1/PD-L1 but had no significant benefit on OS (MSR was estimated to be 1.086 p = 0.117). Besides, combination treatment strategies are more toxic in any grade AEs (RR = 1.13, p < 0.001) and grade 3-5 AEs (RR = 1.81, p < 0.001).

Conclusions

Treatment with PD-1/PD-L1 inhibitors in combination with other antitumor therapies improve patients' ORR, DCR, and PFS compared to anti-PD-1/PD-L1. However, it is regrettable that there is no benefit to OS and an increased risk of AEs in combinatorial therapies.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC9913120 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Efficacy and Safety of PD-1/PD-L1 Checkpoint Inhibitors versus Anti-PD-1/PD-L1 Combined with Other Therapies for Tumors: A Systematic Review.

Zhang Yiru Y Yao Qigu Q Pan Yong Y Fang Xinru X Xu Haoying H Zhao Tingxiao T Zhu Guangqi G Jiang Tianan T Li Shibo S Cao Hongcui H

Cancers 20230122 3

<h4>Objective</h4>In recent years, the anti-programmed cell death protein-1 and its ligand (PD-1/PD-L1) or combination therapies have been recommended as an alternative emerging choice of treatment for oncology patients. However, the efficacy and adverse events of different combination strategies for the treatment of tumors remain controversial.<h4>Methods</h4>PubMed, Embase, Cochrane Library, the American Society of Clinical Oncology (ASCO), and the European Society of Medicine Oncology (ESMO) ...[more]

PMID: 36765640

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Project description:Immune checkpoint inhibitors (ICIs) are recommended as first-line treatment for late-stage non-small cell lung cancer (NSCLC), either as monotherapy or in combination with chemotherapy. However, efficacy and safety comparisons between ICIs as monotherapy and ICIs with chemotherapy are lacking. We searched PubMed, Embase, and Cochrane Library for randomized controlled trials published before February 29th, 2020, with the search terms "immunotherapy" and "chemotherapy". 10 eligible trials were identified with a total of 5,956 patients. Of these patients, 3,204 received immune therapy and 2,752 received chemotherapy. PD-1 inhibitors with chemotherapy improved OS (HR 0.84, 0.77-0.92), PFS (HR 0.80, 0.75-0.85), and objective response rate (ORR) (odds ratio (OR) 2.55, 1.20-5.28) compared to PD-1 inhibitors as monotherapy. In contrast, PD-L1 inhibitors plus chemotherapy showed no significant differences in OS, PFS, or ORR compared with PD-L1 inhibitors as monotherapy. When patients were stratified according to PD-L1 expression level, patients with high PD-L1 expression (≥ 50%) receiving PD-1 inhibitors plus chemotherapy had improved PFS, but not other outcomes, compared to PD-1 inhibitors as monotherapy. In these patients, PD-L1 inhibitors plus chemotherapy showed no significant difference in survival compared with PD-L1 inhibitors. In the low PD-L1 expression group (1%-49%), PD-1 inhibitors plus chemotherapy improved OS and PFS, but no advantage was observed in PD-L1 inhibitors plus chemotherapy in OS, PFS, or ORR compared with PD-L1 inhibitor monotherapy. When comparing PD-1/PD-L1 inhibitors plus chemotherapy with PD-1/PD-L1 inhibitors monotherapy, no significant differences were observed in the rate of immune-related adverse events (AEs). In summary, for treating patients with late-stage NSCLC, PD-1 inhibitors plus chemotherapy have improved efficacy compared with PD-1 inhibitor monotherapy, but PD-L1 inhibitors plus chemotherapy have similar efficacy as PD-L1 monotherapy. Survival benefits of PD-1/PD-L1 inhibitors combined with chemotherapy were particularly significant in patients with low PD-L1 expression levels.Systematic review registrationPROSPERO, identifier CRD42020166678 (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=166678).

Project description:Purpose: The clinical use of immunotherapies targeting programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) is rapid expanding, but the equivalency of these inhibitors remains unclear. We aimed to comprehensively compare the efficacy and safety of PD-1/PD-L1 inhibitors with a systematic review and Bayesian network meta-analysis Methods: We searched PubMed, Web of Knowledge, related reviews and abstracts for randomized controlled trials of five PD-1/PD-L1 inhibitors for patients with solid tumors before November 30th, 2018. We estimated summary hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and odds ratios (ORs) for grade 3-5 treatment-related adverse events (TrAEs) using pairwise and network meta-analysis with random-effects. This study was registered with PROSPERO (#CRD42018116624). Results: Totally, 43 reports of 35 trials comprising 21261 patients were eligible for the analysis. Nivolumab, pembrolizumab, atezolizumab and durvalumab were more effective than control treatment, and no significant differences were identified in OS and PFS between any two inhibitors. Avelumab was associated with significantly inferior OS to nivolumab (HR 1.37, 95%CrI 1.05-1.78) and pembrolizumab (HR 1.33, 95%CrI 1.02-1.73), and with inferior PFS to nivolumab (HR 1.60, 95%CrI 1.03-2.51). Compared with placebo, nivolumab had increased risk of grade 3-5 TrAEs (OR 2.35, 95%CrI 1.35-4.17). Compared with standard-of-care, nivolumab (OR 0.39, 95%CrI 0.28-0.54), pembrolizumab (OR 0.43, 95%CrI 0.30-0.60), atezolizumab (OR 0.37, 95%CrI 0.21-0.64) and avelumab (OR 0.24, 95%CrI 0.12-0.48) significantly reduced grade 3-5 TrAEs. There were not significant differences in grade 3-5 TrAEs between any two inhibitors. Conclusion: This Bayesian network meta-analysis revealed that nivolumab, pembrolizumab, atezolizumab and durvalumab yielded equivalent survival, while avelumab was associated with unfavorable survival. PD-1/PD-L1 inhibitors were comparable in the risk of TrAEs, and safer than conventional therapies.

Dataset Information

Efficacy and Safety of PD-1/PD-L1 Checkpoint Inhibitors versus Anti-PD-1/PD-L1 Combined with Other Therapies for Tumors: A Systematic Review.

Objective

Methods

Results

Conclusions

Publications

Efficacy and Safety of PD-1/PD-L1 Checkpoint Inhibitors versus Anti-PD-1/PD-L1 Combined with Other Therapies for Tumors: A Systematic Review.

Similar Datasets

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