Anti–Programmed Cell Death (PD)-1 Immunotherapy for Malignant Tumor: A Systematic Review and Meta-Analysis

e21700 Background: Immune checkpoint inhibitors of programmed cell death-1 (PD-1) and its ligand (PD-L1) have been new standard of care for non-small cell cancer patients. However, little is known about the difference in efficacy between these two types of drugs. In this study, we aimed to assess the differences between anti-PD-1 and anti-PD-L1 in NSCLC treatment through a systematic review and meta-analysis. Methods: We systematically searched PubMed, CENTRAL, and Embase from January, 2000 to November, 2019. We also reviewed abstracts and presentations from all major conference proceedings. All randomized controlled trials that compared anti-PD-1/anti-PD-L1 with standard treatment in NSCLC cancer patients were selected as candidates. Studies with anti-PD-1 and anti-PD-L1 were screened and paired upon the mirror principle. The primary outcome was the difference in overall survival (OS). As the main results, indirect comparison of anti-PD-1 and anti-PD-L1 were calculated for each mirror group and then pooled using a random-effects model. Results: 16 randomized controlled trials were included for the meta-analysis. Overall, anti-PD-1 exhibited superior OS (HR 0.80, 95% CI 0.68-0.95, P= .01) over anti-PD-L1. Subgroup analysis showed that anti-PD-1 exhibited superior OS over anti-PD-L1 ICIs in combination therapy (HR 0.67, 95% CI 0.54-0.82, P <.01), but not in monotherapy (HR 0.89, 95% CI 0.74-1.06), 2nd line therapy (HR 0.84, 95% CI 0.66-1.06) or 1st line therapy (HR 0.77, 95% CI 0.58-1.03). Conclusions: The results demonstrated that anti-PD-1 exhibited favorable survival outcomes compared to anti-PD-L1 in NSCLC treatment, which provides an important guide for clinicians.

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Predictive effect of molecular and clinical characteristics for the OS and PFS efficacy of anti-PD-1/PD-L1 immunotherapy in patients with NSCLC: a meta-analysis and systematic review

BMJ Open ◽

10.1136/bmjopen-2020-047663 ◽

2021 ◽

Vol 11 (12) ◽

pp. e047663

Author(s):

Rui An ◽

Feng Zhao ◽

Liqian Wang ◽

Jikang Shan ◽

Xianjun Wang

Keyword(s):

Systematic Review ◽

Cell Death ◽

Programmed Cell Death ◽

Clinical Characteristics ◽

Meta Analysis ◽

Objective Response ◽

Smoking History ◽

Secondary Outcome ◽

Secondary Outcome Measure ◽

Predictive Effect

ObjectiveTo evaluate the predictive effect of molecular and clinical characteristics for the efficacy of anti-programmed cell death 1 (PD-1)/programmed cell death ligand-1 (PD-L1) immunotherapy in patients with non-small cell lung cancer (NSCLC).DesignSystematic review and meta-analysis.SettingTwelve randomised controlled trials (RCTs) with 7442 patients were retrieved from all over the world.MethodsElectronic databases were searched for eligible RCTs. The HRs and 95% CIs for overall survival (OS) and progression‐free survival (PFS) for the whole and subgroup population were extracted for meta-analysis using Review Manager V.5.3 software.Primary and secondary outcome measureOS was the primary outcome and PFS was the secondary outcome.ResultsTwelve RCTs with 7442 patients were included. For the trial population, anti-PD-1/PD-L1 immunotherapy significantly improved OS (HR=0.78, 95% CI 0.70 to 0.86, p<0.00001) and objective response rate (ORR) (risk ratio=1.37, 95% CI 1.08 to 1.74, p=0.009). Subgroup analysis results showed an improved OS at PD-L1≥1%, ≥5% and ≥50% levels, and a longer PFS at PD-L1≥5% and ≥50% levels. Moreover, OS and PFS benefits were observed in the non-first line treatment, squamous cell carcinoma histology, male, smoking, non-central nervous system (CNS) metastasis, epidermal growth factor receptor (EGFR) wild-type and Kirsten rat sarcoma viral oncogene homolog (KRAS) mutant subgroups.ConclusionsAnti-PD-1/PD-L1 immunotherapy significantly improved OS and ORR and reduced the rate of Adverse Events (AEs) compared to chemotherapy. PD-L1 expression, line of therapy, histology, sex, smoking history, CNS metastases, EGFR and KRAS mutational status might be potential predictors for the therapeutic effect of anti-PD-1/PD-L1 immunotherapy in specific patients with NSCLC.

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