Dataset Information

Efficacy and safety of anti-PD-1 inhibitor versus anti-PD-L1 inhibitor in first-line treatment of extensive-stage small cell lung cancer: a multicenter retrospective study.

ABSTRACT:

Background

Immunotherapy 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.

Methods

Patients 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.

Results

Of 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.

Conclusions

Anti-PD-1 agents and anti-PD-L1 agents combined with chemotherapy as first-line treatment for ES-SCLC are comparably effective and well tolerated.

SUBMITTER: Qin B

PROVIDER: S-EPMC10795417 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Publications

Efficacy and safety of anti-PD-1 inhibitor versus anti-PD-L1 inhibitor in first-line treatment of extensive-stage small cell lung cancer: a multicenter retrospective study.

Qin Boyu B Xin Lingli L Liang Chen C Li Lingling L Song Qi Q Long Yaping Y Zhang Xiaoling X Wang Dan D Shi Weiwei W Zhang Jing J Hu Yi Y Yang Bo B Xiong Qi Q

BMC cancer 20240117 1

<h4>Background</h4>Immunotherapy 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.<h4>Methods</h4>Patients with pathologically o ...[more]

PMID: 38233798

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Project description:BackgroundThe prognosis of small cell lung cancer (SCLC) patients is poor, and the standard first-line treatment for limited-stage small cell lung cancer (LS-SCLC) is still chemotherapy and thoracic radiotherapy. The primary objectives of our study were to confirm the superior efficacy of first-line immune checkpoint inhibitors (ICIs) plus etoposide and platinum (EP) for LS-SCLC and find crucial biomarkers.MethodsWe analyzed LS-SCLC patients from three medical centers, employing propensity score matching for group comparability. Survival outcomes were estimated by Kaplan-Meier and Cox regression analyses. Additionally, we conducted univariate and multivariate analyses to investigate potential predictive factors.ResultsAmong 150 patients in our study, we successfully matched 41 pairs. The median overall survival (OS) was 29.5 months in the EP + ICIs group and 20.0 months in the EP group {hazard ratio (HR) =0.64 [95% confidence interval (CI): 0.41-1.02], P=0.059}. The median progression-free survival (PFS) was significantly extended in the EP + ICIs group (14.6 months), compared to the EP group (8.6 months) [HR =0.42 (95% CI: 0.28-0.63), P<0.001]. After matching, patients receiving chemo-immunotherapy had a median OS of 36.1 months, significantly surpassing those receiving chemotherapy alone (19.0 months) [HR =0.51 (95% CI: 0.28-0.93), P=0.02]. And the patients in the EP + ICIs group also had longer PFS after matching [HR =0.42 (95% CI: 0.25-0.71), P=0.001]. No significant difference in the objective response rate (ORR) and treatment-related adverse events (trAEs) between the two groups was found (ORR: EP: 81.0%, EP + ICIs: 90.0%, P=0.14; trAEs: EP: grade 1-2, 49.3%; grade 3-4, 42.5%; EP + ICIs: grade 1-2, 40.0%; grade 3-4, 49.1%, P=0.62). The multivariate analysis presented that the history of immunotherapy [EP + PD-1 inhibitors: HR =0.33 (95% CI: 0.17-0.62), P=0.001; EP + PD-L1 inhibitors: HR =0.18 (95% CI: 0.06-0.60), P=0.005] and baseline lung immune prognostic index (LIPI) [intermediate: HR =2.22 (95% CI: 1.20-4.13), P=0.01; poor: HR =2.03 (95% CI: 0.71-5.77), P=0.18] were independent prognostic factors for PFS among all LS-SCLC cases. However, no independent prognostic factor was identified for OS.ConclusionsOur real-world data showed promising clinical efficacy and tolerable safety of first-line programmed cell death protein 1 (PD-1) inhibitors or programmed cell death ligand 1 (PD-L1) inhibitors in cases with LS-SCLC. Additionally, LIPI may serve as a valuable prognostic factor.

Project description:BackgroundImmunotherapy 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.MethodsWe 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).ResultsFour 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.ConclusionsICI 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 pointsSignificant 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 addsThis 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.

Project description:BackgroundImmunotherapy in combination with platinum-etoposide (EP) chemotherapy has been approved as a first-line treatment for extensive-stage small cell lung cancer (ES-SCLC). However, real-world (RW) data regarding the use of immune checkpoint inhibitors (ICIs) in ES-SCLC are lacking. We aimed to assess the differences between programmed death protein 1 (PD-1) inhibitors and programmed death ligand 1 (PD-L1) inhibitors, both in conjunction with EP chemotherapy, as first-line treatment for ES SCLC.MethodsWe conducted a real-world, multicenter, retrospective cohort, controlled study to compare the prognosis, efficacy, and safety of PD-1 and PD-L1 inhibitors in ES-SCLC patients when used along with chemotherapy. Each patient received up to six cycles of etoposide, carboplatin, or cisplatin combined with ICI drugs, including PD-1 and PD-L1 inhibitors. The primary endpoints were investigator-assessed progression-free survival (PFS) and overall survival (OS). The secondary endpoints were the investigator-assessed objective response rate (ORR) and disease control rate (DCR) according to the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1).ResultsBetween January 2017 and December 2021, 194 patients with ES-SCLC from three clinical centers in a PLA general hospital were included in our study, including 93 patients in the PD-1 group and 101 patients in the PD-L1 group. At the time of data cutoff, progression-free survival in the PD-1 group (median PFS, 6.8 months; 95% CI, 5.3-8.1) was similar to that in the PD-L1 group (median PFS, 6.4 months; 95% CI, 5.5-7.5); the stratified hazard ratio for PFS was 1.12 (95% CI, 0.83-1.53; P = 0.452). The median OS was similar in the PD-1 and PD-L1 groups (15.8 m vs. 17.7 m, P = 0.566); the hazard ratio was 0.90 (95% CI, 0.62-1.30, P = 0.566). The two groups had comparable investigator-assessed confirmed objective response rates (ORR) (76.3% vs. 76.2%). Adverse effect (AE)-related discontinuation occurred in 4 (4.3%) patients in the PD-1 group and 2 (2.0%) patients in the PD-L1 group. Deaths due to AEs of any cause occurred in 2 (2.2%) patients in the PD-1 inhibitor group and 1 (1.0%) patient in the PD-L1 inhibitor group.ConclusionsOur research revealed that there were no significant differences in efficacy or prognosis between PD-1 inhibitor + EP chemotherapy and PD-L1 inhibitor + EP chemotherapy. The two groups seemed to have comparable safety profiles, but the number of discontinuation or death events was too small to draw a firm conclusion.

Dataset Information

Efficacy and safety of anti-PD-1 inhibitor versus anti-PD-L1 inhibitor in first-line treatment of extensive-stage small cell lung cancer: a multicenter retrospective study.

Background

Methods

Results

Conclusions

Publications

Efficacy and safety of anti-PD-1 inhibitor versus anti-PD-L1 inhibitor in first-line treatment of extensive-stage small cell lung cancer: a multicenter retrospective study.

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