Comparison of efficacy and safety of PD-1/PD-L1 combination therapy in first-line treatment of advanced NSCLC: an updated systematic review and network meta-analysis.
The use of immune checkpoint inhibitors has led to an increase in randomized controlled trials exploring various first-line combination treatment regimens. With the introduction of new PD-1/PD-L1 inhibitors, there are now more clinical options available. For the first time, the AK105 monoclonal antibody Penpulimab, developed in China, was included. The AK105-302 Phase III trial studied the efficacy and safety of Penpulimab combined with chemotherapy in patients with advanced or metastatic squamous NSCLC. To determine the optimal treatment options, we conducted an updated network meta-analysis to compare the effectiveness and safety of these regimens.
The system retrieves data from Chinese and English electronic databases, Clinical Trials, and the gov Clinical Trial Registration website up to September 6, 2023. The study indirectly compared the efficacy and safety of PD-1/PD-L1 combination regimens, including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), all-grade adverse events, and above-grade III adverse events. Subgroup analyses were conducted based on programmed death ligand 1 (PD-L1) level, histological type, ECOG score, sex, and smoking history.
Nineteen RCTS were included, with a total of ten thousand eight hundred patients. Penpulimab plus chemotherapy (Pen + CT) provided the best OS (HR = 0.55, 95% CI 0.38-0.81) for PD-L1 patients with non-selective advanced NSCLC. Except Nivolumab plus Ipilimumab (Niv + Ipi), other PD-1/PD-L1 combination therapies significantly extended PFS compared with CT, and Nivolumab plus Bevacizumab combined with chemotherapy (Niv + Bev + CT) (HR = 0.43, 95% CI 0.26-0.74) provided the best PFS benefit and was comparable to Pen + CT (HR = 1.0) for PFS prolongation. For ORR, except Niv + Ipi, all the other regimens significantly improved ORR compared with CT. In terms of safety, except Tor + CT, the incidence of any-grade AEs or grade ≥ 3 adverse events may be higher than those of chemotherapy. The subgroup analysis revealed that for patients with PD-L1 levels below 1%, treatment with Tor + CT resulted in the best progression-free survival (HR = 0.47, 95% CI 0.25-0.86). For patients with PD-L1 levels of 1% or higher, Sintilimab plus chemotherapy (Sin + CT) (HR = 0.56, 95% CI 0.31-0.99) and Camrelizumab plus chemotherapy (Cam + CT) (HR = 0.43, 95% CI 0.28-0.64) were associated with the best overall survival and progression-free survival, respectively. For patients with SqNSCLC, combined immunotherapy may provide greater survival benefits. For patients with Non-sqNSCLC, Niv + Bev + CT and Tor + CT were associated with optimal PFS and OS, respectively. Cam + CT provided the best PFS in male patients with a history of smoking and an ECOG score of 0. In both female and non-smoking patient subgroups, Pem + CT was associated with the best PFS and OS benefits.
For patients with advanced non-selective PD-L1 NSCLC, two effective regimens are Pen + CT and Niv + Bev + CT, which rank first in OS and PFS among all patients. Cam + CT and Tor + CT have advantages for OS in patients with SqNSCLC and Non-sqNSCLC, respectively. Niv + Ipi + CT provided the best OS benefit for patients with an ECOG score of 0, while Pem + CT may be the most effective treatment for patients with an ECOG score of 1. Pem + CT has a better effect on female patients and non-smokers. Sin + CT was found to be the most effective treatment for male patients and the smoking subgroup, while Cam + CT was found to be the most effective for PFS. In addition, Tor + CT was associated with the best PFS for patients with negative PD-L1 expression. Pem + CT was found to significantly improve both PFS and OS compared to CT alone. For patients with positive PD-L1 expression, Sin + CT and Cam + CT were found to be optimal for OS and PFS, respectively. It is important to note that, with the exception of Tor + CT, the toxicity of the other combinations was higher than that of CT alone.
Yang Y
，Chen W
，Dong L
，Duan L
，Gao P
... -
《-》
Infiltration of CD8(+) cytotoxic T-cells and expression of PD-1 and PD-L1 in ovarian clear cell carcinoma.
Ovarian clear cell carcinoma (OCCC) is resistant to chemotherapy, with limited treatment options for advanced and recurrent disease. The prevalence of OCCC differs by region. Assessing the expression of programmed cell death ligand 1 (PD-L1), PD-1, and CD8+T cell infiltration in OCCC is crucial, as their correlation with patient survival may provide valuable prognostic insights. We collected data from 36 samples from 18 OCCC patients, including 18 pairs of tumors and adjacent nonneoplastic samples. The optimized multiplex immunofluorescence technique was used to stain paraffin sections for immune factors related to the immune microenvironment of OCCC and clinical prognosis. The expression of PDL1 and PD1 in the tumor cells and tumor stromal cells was not significantly correlated with prognosis. Professional quantitative pathological analysis software was used to count the CD8+ cytotoxic T-cells in tumor regions and adjacent nonneoplastic regions in postoperative specimens. There were more CD8+ cytotoxic T-cells in the adjacent nonneoplastic areas than in the tumor tissue samples (p < 0.001). Further analysis revealed that a difference in cell density between CD8+ non-tumor-infiltrating lymphocytes (NTILs) and CD8+ tumor-infiltrating lymphocytes (TILs) exceeding 70 cells/mm2 was associated with poorer progression-free survival (PFS) (p = 0.042). In adjacent nonneoplastic regions, worse PFS was significantly observed in patients with high CD8+ T-cell expression in both total and stromal cells than those with low expression (p = 0.012 vs p = 0.007). The presence of CD8+ T-cells had significant potential for predicting the prognosis of patients with OCCC, which lays a foundation for the development of biomarkers for immune checkpoint blockade treatment response in OCCC patients.
Fu M
，Zhou H
，Yang J
，Cao D
，Yuan Z
... -
《Scientific Reports》
Expression and relationship of PD-L1, CD24, and CD47 in hepatitis B virus associated hepatocellular carcinoma.
Immune checkpoint inhibitor (ICI) therapy is the new standard treatment for advanced or metastatic hepatocellular carcinoma (HCC); however, many patients still fail to respond. This study explored the expression and prognosis of programmed death ligand 1 (PD-L1), cluster of differentiation 24 (CD24), and cluster of differentiation 47 (CD47) in patients with hepatitis B virus-associated HCC (HBV-associated HCC). We analyzed sequencing data from the Cancer Genome Atlas (TCGA) and investigated the expression of PD-L1, CD24, and CD47 in HBV-associated HCC patients by immunohistochemistry and their relationship with prognosis and clinicopathological factors. HCC data from the TCGA database show that PD-L1 was substantially correlated with various immune cells. In 67 patients with HBV-associated HCC, high PD-L1 and CD24 expression levels were related to poor overall survival (OS) and progression-free survival (PFS). PD-L1 expression was significantly associated with the staging of HBV-associated HCC (p = 0.011) and Ki67 expression (p = 0.024). Correlation analysis between variables reveals that PD-L1 was significantly positively correlated with CD24 and CD47. High expression of PD-L1 and CD24 are risk factors for poor prognosis in HBV-associated HCC patients following curative resection. PD-L1 is significantly correlated with CD24 and CD47.
Lin A
，Wang M
，Wang Z
，Lin J
，Lin Z
，Lin S
，Lu S
，Lin H
，Tang H
，Huang X
... -
《Scientific Reports》
Association Between PD-L1 Expression and Efficacy of Chemoimmunotherapy in Extensive-stage Small Cell Lung Cancer.
Few studies have examined the association between programmed cell death ligand 1 (PD-L1) expression in small cell lung cancer and the effect of chemoimmunotherapy.
Patients diagnosed with extensive-stage small cell lung cancer at our hospital between September 2019 and August 2023, who were treated with atezolizumab plus carboplatin and etoposide and had pathological tissue immunostained with SP142, were retrospectively examined to determine whether treatment efficacy differed depending on the expression of PD-L1.
Twenty-nine patients were analyzed. SP142 immunostaining revealed that the tumor cell (TC) score was 3, 2, 1, and 0 in 1, 0, 0, and 28 cases, respectively. The tumor-infiltrating cell (IC) score was 3, 2, 1, and 0 in 1, 0, 5, and 23 cases, respectively. The median progression-free survival (PFS) of the patients who tested positive and negative for TC was 13 and 5 months, respectively [hazard ratio (HR)=0.041; 95% confidence interval (CI)=0.000-36.225; p=0.109]; and the median overall survival (OS) was 13 and 7.5 months (HR=0.046; 95%CI=0.000-948.833; p=0.338), respectively. The median PFS of the patients who tested positive and negative for IC was 8 and 4 months, respectively (HR=0.216; 95%CI=0.061-0.765; p=0.004); the median OS was 15 and 8 months, respectively (HR=0.573; 95%CI=0.168-1.955; p=0.346).
Patients who tested positive for IC had a significantly longer PFS than those who tested negative. Thus, PD-L1 expression may be a predictive factor of efficacy of chemoimmunotherapy in extensive-stage small cell lung cancer.
Tsuruoka K
，Tamura Y
，Shimazu Y
，Arai M
，Mitsuya S
，Funamoto T
，Tsuji H
，Matsunaga N
，Nakamura T
，Ikeda S
，Kawabata S
，Imagawa A
，Fujisaka Y
... -
《-》
ResearchGate
(全网免费下载)
钛学术
(全网免费下载)
