Dataset Information

Efficacy and safety of PD-1/PD-L1 inhibitor plus chemotherapy versus chemotherapy alone as first-line treatment for extensive-stage small cell lung cancer: A systematic review and meta-analysis.

ABSTRACT:

Background

Immunotherapy has afforded new treatment options for extensive small cell lung cancer (ES-SCLC). However, reports on the effectiveness of immune checkpoint inhibitors (ICIs) combined with chemotherapy on survival in ES-SCLC patients are inconsistent. Therefore, we conducted a meta-analysis on the efficacy and safety of ICI combined with chemotherapy for ES-SCLC.

Methods

We searched for randomized controlled clinical trials related to first-line treatment of ES-SCLC with ICI combined with chemotherapy in PUBMED, ESMO, ASCO, and WCLC since 2018. The primary outcome was overall survival (OS).

Results

Four studies were included. Compared to chemotherapy alone, ICI in combination with chemotherapy as first-line treatment reduced the risk of death (hazard ratio [HR]: 0.76; 95% CI: 0.68-0.86; P < 0.00001) and disease progression (HR: 0.76; 95% CI: 0.68-0.84; P < 0.00001). The objective response rate (ORR) with ICI plus chemotherapy was significantly higher than that with chemotherapy alone (HR: 1.10; 95% CI: 1.02-1.19, P = 0.01). The duration of response (DoR) rate at one year was also better with ICI plus chemotherapy (HR: 3.46; 95% CI: 2.24-5.33; P < 0.00001). Security analysis revealed that the incidence of immune-mediated adverse events (imAEs) (HR: 3.77; 95% CI: 1.99-7.15, P < 0.0001) and grade 3/4 imAEs (HR: 7.01; 95% CI: 2.48-19.81; P = 0.0002) increased significantly with ICI plus chemotherapy.

Conclusions

ICI combined with chemotherapy as first-line treatment can significantly improve the OS and progression-free survival (PFS) of ES-SCLC patients, but the toxicity caused by immunotherapy should be carefully considered.

Key points

Significant findings of the studyOur meta-analysis shows that PD-L1/PD-1 plus chemotherapy can significantly improve the OS and PFS of ES-SCLC patients when used as first-line therapy.

What this study adds

This study fills gaps regarding the efficacy of immunotherapy combined with chemotherapy as first-line treatment for ES-SCLC, and provides better evidence for the use of PD-L1/PD-1 immunotherapy plus chemotherapy for patients with ES-SCLC.

SUBMITTER: Zhang S

PROVIDER: S-EPMC7705912 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Efficacy and safety of PD-1/PD-L1 inhibitor plus chemotherapy versus chemotherapy alone as first-line treatment for extensive-stage small cell lung cancer: A systematic review and meta-analysis.

Zhang Shuang S Li Shuang S Cheng Ying Y

Thoracic cancer 20201015 12

<h4>Background</h4>Immunotherapy has afforded new treatment options for extensive small cell lung cancer (ES-SCLC). However, reports on the effectiveness of immune checkpoint inhibitors (ICIs) combined with chemotherapy on survival in ES-SCLC patients are inconsistent. Therefore, we conducted a meta-analysis on the efficacy and safety of ICI combined with chemotherapy for ES-SCLC.<h4>Methods</h4>We searched for randomized controlled clinical trials related to first-line treatment of ES-SCLC with ...[more]

PMID: 33058504

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Project description:Background:Programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitor monotherapy has been approved as second-line or later therapy in advanced non-small-cell lung cancer (NSCLC). The study aimed to compare the clinical outcomes of PD-1 inhibitor plus chemotherapy with PD-1/PD-L1 inhibitor monotherapy as second-line or later therapy in advanced NSCLC. Methods:The clinical data of patients with advanced NSCLC who received PD-1/PD-L1 inhibitors as second-line or later line therapy was retrospectively collected. Patients were assigned to one of the two groups according to the therapeutic modality used: PD-1/PD-L1 inhibitor monotherapy group or PD-1 inhibitor plus chemotherapy combination therapy group. Disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were evaluated between the two groups. The prognostic effect of the derived neutrophil-to-lymphocyte ratio (dNLR) and lactate dehydrogenase (LDH) on the outcomes was also evaluated. Results:From April 2017 to October 2019, a total of 84 patients were enrolled in the current study. Twenty-six patients (PD-1 inhibitor, n = 25; PD-L1 inhibitor, n = 1) received PD-1/PD-L1 inhibitor monotherapy, and fifty-eight patients received PD-1 inhibitor plus chemotherapy. The chemotherapy regimens used were as follows: liposome paclitaxel (n = 15); nab-paclitaxel (n = 12); docetaxel (n = 9); pemetrexed (n = 6); and others (n = 16). The DCR and OS were not significantly different between the two groups. The PFS of the monotherapy group was longer than that of the combination therapy group (mPFS: 9.6 vs. 4.6 months, P = 0.01). Univariate and multivariate analyses suggested that LDH and sex were independent prognostic factors of PFS. In the second-line therapy subgroup of 38 patients, OS and PFS were not significantly different between the two groups. In the subgroup of 46 patients treated beyond the 2nd line, the monotherapy group had a longer PFS (mPFS: 9.6 vs. 4.2 months, P = 0.01). The incidence of any-grade adverse events was not significantly different between the monotherapy group and the combination therapy group (19.2 vs. 18.9%, P = 1.000). One patient in the PD-1 inhibitor plus chemotherapy group died of immune-related pneumonitis. Conclusion:The clinical outcomes of PD-1 inhibitor plus chemotherapy as second-line or later therapy were similar to those of PD-1/PD-L1 inhibitor alone in advanced NSCLC.

Project description:BackgroundImmunotherapy targeting PD-1/PD-L1 has revolutionized the treatment of extensive-stage small cell lung cancer (ES-SCLC). However, clinical trials suggest differential efficacy of anti-PD-1 agents and anti-PD-L1 agents in first-line treatment of ES-SCLC. This retrospective multicenter study aimed to compare the efficacy and safety of anti-PD-1 agents versus anti-PD-L1 agents in first-line treatment of ES-SCLC in real-world practice.MethodsPatients with pathologically or cytologically confirmed ES-SCLC treated with platinum plus etoposide combined with anti-PD-1 or PD-L1 agents as first-line treatment in different centers of PLA General Hospital between January 2017 and October 2021 were included for this study. Survival outcomes and safety were compared between patients receiving anti-PD-1 and PD-L1 agents.ResultsOf the total 154 included patients, 68 received anti-PD-1 agents plus chemotherapy (PD-1 group), and 86 received anti-PD-L1 agents plus chemotherapy (PD-L1 group). Progression-free survival (PFS) and overall survival (OS) in the entire cohort were 7.6 months (95% confidence interval [CI]: 6.5-8.2 months) and 17.4 months (95% CI: 15.3-19.3 months), respectively. Median PFS and OS were comparable between the PD-1 group and PD-L1 group (PFS: 7.6 months vs. 8.3 months, HR = 1.13, 95% CI: 0.79-1.62, p = 0.415; OS: 26.9 months vs. 25.6 months, HR = 0.96, 95% CI: 0.63-1.47, p = 0.859. The objective response rate and disease control rate were comparable between the two groups: 79.4% vs. 79.1% and 92.6% vs. 94.2%, respectively. The 6-month, 12-month, and 18-month PFS and OS rates were slightly higher in the PD-L1 group than in the PD-1 group, while the 24-month PFS rate was slightly higher in the PD-1 group than in the PD-L1 group. Stratified analysis showed that locoregional thoracic radiotherapy and normal lactate dehydrogenase level were independent predictors of better OS in ES-SCLC patients treated with first-line chemotherapy plus ICI. Adverse events were not significantly different between the two groups.ConclusionsAnti-PD-1 agents and anti-PD-L1 agents combined with chemotherapy as first-line treatment for ES-SCLC are comparably effective and well tolerated.

Dataset Information

Efficacy and safety of PD-1/PD-L1 inhibitor plus chemotherapy versus chemotherapy alone as first-line treatment for extensive-stage small cell lung cancer: A systematic review and meta-analysis.

Background

Methods

Results

Conclusions

Key points

What this study adds

Publications

Efficacy and safety of PD-1/PD-L1 inhibitor plus chemotherapy versus chemotherapy alone as first-line treatment for extensive-stage small cell lung cancer: A systematic review and meta-analysis.

Similar Datasets

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