The landscape of immune checkpoint inhibitor plus chemotherapy versus immunotherapy for advanced non‐small‐cell lung cancer: A systematic review and meta‐analysis

Wang, Chengdi; Qiao, Wenliang; Jiang, Yuting; Zhu, Min; Shao, Jun; Wang, Tao; Liú, Dan; Liu, Weimin

doi:10.1002/jcp.29371

Cited by 53 publications

(48 citation statements)

References 51 publications

(77 reference statements)

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“…Despite these strengths, there have been several controversies. Three studies associated with NMA had been conducted to figure out the best PD-1/L1 inhibitor for advanced NSCLC patients in the first-line settings (51)(52)(53). Our results were generally consistent with the previous studies, which had all indicated the combination of pembrolizumab to be better than other combined therapies or chemotherapies for patients with relatively high expression of PD-L1.…”

Section: Discussionsupporting

confidence: 89%

Compare the efficacy and safety of programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) inhibitors for advanced non-small cell lung cancer: a Bayesian analysis

Liang

Sui

et al. 2020

Transl Lung Cancer Res

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Background: Inhibitors of programmed cell death-1 (PD-1) and its ligand (PD-L1) have represented a novel approach for the management of advanced non-small cell lung cancer (NSCLC). In this study, we aimed to estimate five anti-PD-1/L1 agents (nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab) using network meta-analyses (NMAs) and the Bayesian method to provide suggestions for advanced NSCLC treatments.Methods: We searched PubMed, Web of Science, Embase, and the Wiley Online Library for eligible studies published up to March 2020. Both pairwise analyses and NMAs were conducted with clinical outcomes, including overall survival (OS), progression-free survival (PFS), objective response rate, and the incidences of adverse events. Results were presented in several patient populations according to treatment lines and PD-L1 status.Results: Nineteen randomized clinical trials (RCTs) involving 11,456 patients were included in our study.PD-1/L1 inhibitors showed significant benefits over chemotherapies in OS regardless of tumor PD-L1 status [first-line settings: OS =0.85, 95% CI (0.77, 0.94), I 2 =37%; second-or further-line settings: OS =0.77, 95% CI (0.71, 0.84), I 2 =37%]. The combined regimen of pembrolizumab and chemotherapy stood out to be the most effective and safest for patients in the first-line settings. Pembrolizumab monotherapy was showed to be the best especially for patients with PD-L1 ≥50%. In the subsequent-line settings, nivolumab ranked the best in improving the survival of patients, and durvalumab had the greatest effect in tumor shrinkage.Atezolizumab, followed by nivolumab, ranked the safest in reducing adverse events, whereas durvalumab was showed with the largest side effects among the five inhibitors. Conclusions:The combination of pembrolizumab with chemotherapy is suitable for advanced NSCLC patients who have not received any systematic treatments before, and pembrolizumab monotherapy should also be considered, especially for patients with highly-expressed PD-L1 (≥50%). Nivolumab is the best option for patients with advanced NSCLC whose tumors have progressed following chemotherapies or combined modalities of treatments including chemotherapy. However, our results need to be further validated in future head-to-head clinical trials.

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Section: Discussionsupporting

confidence: 89%

Compare the efficacy and safety of programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) inhibitors for advanced non-small cell lung cancer: a Bayesian analysis

Liang

Sui

et al. 2020

Transl Lung Cancer Res

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“…Immune checkpoint inhibitors (ICIs) plus chemotherapy are recommended as the optimal first‐line therapy for patients with advanced NSCLC ( 9 ). A meta-analysis ( 12 ) found that overall survival (OS) and progression-free survival (PFS) advantages of ICI therapies were observed in patients with NSCLC with low or high programmed cell death 1 ligand 1 (PD‐L1) expression levels but not in intermediate PD‐L1 TPS patients. Update data for the KEYNOTE-189 study found that regardless of PD-L1 positivity, both median OS and PFS improved in the pembrolizumab combination chemotherapy group in patients with metastatic NSCLC ( 13 ).…”

Section: Introductionmentioning

confidence: 99%

Prognostic Significance of SUVmax Combined With Lactate Dehydrogenase in Advanced Lung Cancer Patients Treated With Immune Checkpoint Inhibitor Plus Chemotherapy: A Retrospective Study

Wang

et al. 2021

Front. Oncol.

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PurposeThis research aims to investigate the predictive capacity of PET/CT quantitative parameters combined with haematological parameters in advanced lung cancer patients treated with immune checkpoint inhibitor (ICI) plus chemotherapy.MethodsA total of 120 patients who underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) were enrolled before therapy. The following parameters were calculated: the maximum, mean, and peak standardized uptake value (SUVmax, SUVmean, and SUVpeak, respectively); total tumour volume (MTV) and total lesion glycolysis (TLG); and whole-body metabolic values (MTVwb, TLGwb, SUVmeanwb, and SUVmaxwb). Lactate dehydrogenase (LDH) levels, absolute neutrophil count, absolute platelet count, albumin levels and derived neutrophil to lymphocyte ratio (dNLR) were also computed. The associations between the variables and therapy outcome (evaluated by iRECIST) were analyzed.ResultsBased on iRECIST, 32 of 120 patients showed iPD, 43 iSD, 36 iPR and 9 iCR. Multivariate analysis found that SUVmax, MTVwb, LDH and absolute platelet count were associated with treatment response (P =0.015, P =0.005, P <0.001 and P =0.015, respectively). Kaplan-Meier survival analyses showed that SUVmax ≥11.42 and LDH ≥245 U/L were associated with shorter OS (P = 0.001 and P = 0.004, respectively). Multivariate Cox regression revealed that SUVmax and LDH alone were not correlated with survival prognosis (p>0.05), but the combination of SUVmax and LDH was independently associated with OS (P=0.015, P=0.001, respectively). The median survival time (MST) for the low (LDH<245 and SUVmax<11.42), intermediate(LDH<245 or SUVmax<11.42), and high(SUVmax≥11.42 and LDH≥245) groups was 24.10 months (95% CI: 19.43 to 28.77), 17.41 months (95% CI: 15.83 to 18.99), and 13.76 months (95% CI: 12.51 to 15.02), respectively.ConclusionThis study identified that SUVmax plus LDH correlated with the survival outcome in patients with advanced lung cancer receiving PD-1/PD-L1 blockade plus chemotherapy.

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“…A number of key practice points are suggested by the findings of this meta-analysis. Although there is increasing evidence in the first-line setting that combination PD-1 blockade plus chemotherapy with or without the antiangiogenesis agent bevacizumab or with or without a CTLA-4 inhibitor ipilimumab is the optimal treatment for patients with PD-L1 less than 50% or those with PD-L1 50% or greater with a high burden of disease ( 35 , 68–77 ), for patients unsuitable for combination therapy or those who prefer to spare chemotherapy toxicity, the choice between PD-1 blockade monotherapy and chemotherapy remains important. This meta-analysis supports the choice of PD-1 blockade over platinum doublet chemotherapy in patients with PD-L1 50% or greater, yielding higher ORR (39.7% vs 29.0%), 2-year PFS (24.6% vs 5.6%), and 3-year OS (38.3% vs 20.4%) rates.…”

Section: Discussionmentioning

confidence: 99%

Response Rate and Survival at Key Timepoints With PD-1 Blockade vs Chemotherapy in PD-L1 Subgroups: Meta-Analysis of Metastatic NSCLC Trials

Man

Millican

Mulvey

et al. 2021

JNCI Cancer Spectrum

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Background PD-L1 expression (PD-L1) on tumor cells with or without immune cells is widely reported in clinical trials of PD-1 blockade in metastatic non-small cell lung cancer (NSCLC). Various cutpoints have been studied. Methods We performed a systematic search of MEDLINE, EMBASE and conference proceedings up to December 2019 for randomized and non-randomized clinical trials of anti-PD-1 or anti-PD-L1 monotherapy in metastatic NSCLC. We retrieved data on objective response rate (ORR), 1 year (1yr PFS) and 2 year progression-free survival (2yr PFS), and 2 year (2yr OS) and 3 year overall survival (3yr OS) in various PD-L1 subgroups. Results were pooled and analysed based on different cutpoints, with non-randomized comparisons made to pooled chemotherapy outcomes. Results 9,810 patients in twenty-seven studies were included. In treatment-naïve patients, benefits with PD-1 blockade over chemotherapy were seen in ORR in patients having PD-L1 ≥50%, in 2yr OS for PDL1 ≥1%, and in 1yr PFS, 2yr PFS and 3yr OS for unselected patients. First-line PD-1 blockade compared to chemotherapy demonstrated higher ORR, 2yr PFS and 3yr OS if PD-L1 ≥50%; lower ORR, higher 2yr PFS and similar 3yr OS if PD-L1 1-49%; and lower ORR, similar 1yr PFS and lower 2yr OS if PD-L1 <1%. In previously treated patients, PD-1 blockade demonstrated similar or superior outcomes to chemotherapy in all PD-L1 subgroups. Conclusions PD-L1 should guide the choice of PD-1 blockade versus chemotherapy in treatment-naïve patients. In previously treated patients, PD-1 blockade provides a favourable outcome profile to chemotherapy in all PD-L1 subgroups.

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The landscape of immune checkpoint inhibitor plus chemotherapy versus immunotherapy for advanced non‐small‐cell lung cancer: A systematic review and meta‐analysis

Cited by 53 publications

References 51 publications

Compare the efficacy and safety of programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) inhibitors for advanced non-small cell lung cancer: a Bayesian analysis

Compare the efficacy and safety of programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) inhibitors for advanced non-small cell lung cancer: a Bayesian analysis

Prognostic Significance of SUVmax Combined With Lactate Dehydrogenase in Advanced Lung Cancer Patients Treated With Immune Checkpoint Inhibitor Plus Chemotherapy: A Retrospective Study

Response Rate and Survival at Key Timepoints With PD-1 Blockade vs Chemotherapy in PD-L1 Subgroups: Meta-Analysis of Metastatic NSCLC Trials

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