3.Expert consensus on PD-L1 expression testing in esophageal carcinoma in China.
Li Yan XUE ; Yin LI ; Jing HUANG
Chinese Journal of Oncology 2023;45(4):291-297
In recent years, immunotherapy represented by immune checkpoint inhibitors programmed death 1 (PD-1) has made great progress in the treatment of esophageal cancer and is rewriting the global paradigm for the treatment of esophageal cancer. According to current data, only a small number of patients with esophageal cancer could benefit from immunotherapy. Therefore, it is a challenge to screen the potential beneficiaries of PD-1 inhibitors. Studies have shown that the expression level of programmed death-ligand 1 (PD-L1) in esophageal cancer is closely associated with the efficacy of PD-1 inhibitors, and PD-L1 is the most important predictive biomarker of the efficacy of PD-1 inhibitors. With the clinical application of different PD-1 inhibitors and PD-L1 protein expression detection platforms, clarifying the clinical significance and timing of detection of PD-L1 protein expression in esophageal cancer, and establishing a standardized PD-L1 testing procedure, are of great significance to improve the accuracy of detection and reduce the difference between laboratories, so as to maximize the therapeutic benefits for patients. This consensus was finally reached, based on the combination of literature, expert experience, and internal discussion and voting of committee members, to provide an accurate and reliable evidence for clinicians to make decisions.
Humans
;
B7-H1 Antigen/metabolism*
;
Immune Checkpoint Inhibitors/therapeutic use*
;
Consensus
;
Esophageal Neoplasms/drug therapy*
;
Immunotherapy/methods*
;
Lung Neoplasms/pathology*
4.Evaluation of the predictive effect of PD-L1 expression on survival in early triple-negative breast cancer.
Jian YUE ; Xue WANG ; An Jie ZHU ; Ding Yuan WANG ; Song Lin GAO ; Nan Lin HU ; Yi Ran SI ; Fang Chao ZHENG ; Jie JU ; Zheng WANG ; Peng YUAN
Chinese Journal of Oncology 2023;45(11):948-954
Objectives: To find the prognostic factors related to early triple-negative breast cancer to optimize the therapeutic strategies, and explore the influence of programmed cell death ligand-1(PD-L1)expression in early triple-negative breast cancer on its prognosis, so as to provide support for clinical treatment decisions. Methods: Early triple-negative breast cancer patients treated at the National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences during 1st June, 2009 and 31st Oct, 2015 were enrolled in this study. All the clinicopathological data of patients were collected, and the paraffin sections of the surgical specimens were stained with estrogen receptor, progesterone receptor, human epidermal growth factor receptor-2, secreted protein acidic and rich in cysteine (SPARC), androgen receptor, PD-L1 and other antibodies by the immunohistochemical method. Kaplan-Meier survival and Cox regression curves were used for survival analysis of relevant clinical and pathological results and nomogram survival prediction models were established to explore the influence of relevant factors on the prognosis. Results: A total of 205 patients with triple-negative breast cancer were enrolled. Ninety patients (43.9%) were PD-L1 positive. The median follow-up time was 63 months. Thirty-seven patients were relapsed or recurrent and 16 patients were dead. The 5-year disease-free survival (DFS) rate and overall survival (OS) rate were 86.1% (95% CI: 81.4%-90.8%) and 93.6% (95% CI: 91.0%-97.6%), respectively, in the general population. Univariate Cox regression analysis showed that PD-L1 expression and lymph node metastasis were correlated with DFS and OS (P<0.05). In multivariate analysis, PD-L1 expression was an independent influencing factor of DFS, with PD-L1 positive patients possessing a significant survival benefit in DFS (HR=0.31, 95% CI: 0.13-0.73). Lymph node metastasis was an independent influencing factor of OS, and OS was significantly shortened in patients with positive lymph node metastasis (HR=3.24, 95% CI: 1.15-9.17). PD-L1, lymph node metastasis, menopausal status, Ki-67 index and adjuvant chemotherapy regimen were included to establish the 1- and 3-year DFS and OS nomogram prediction models, resulting in C indices of 0.698 and 0.748, respectively. Conclusions: PD-L1 expression is a predictive biomarker of good prognostic factor in triple-negative breast cancer patients. DFS is significantly prolonged in PD-L1 positive patients and OS also shows a prolongation trend. The nomogram prognosis prediction models have reference values for adjuvant chemotherapy in this patient group.
Humans
;
Female
;
Lymphatic Metastasis
;
B7-H1 Antigen/metabolism*
;
Triple Negative Breast Neoplasms/pathology*
;
Breast Neoplasms
;
Osteonectin/therapeutic use*
;
Prognosis
5.Evaluation of the predictive effect of PD-L1 expression on survival in early triple-negative breast cancer.
Jian YUE ; Xue WANG ; An Jie ZHU ; Ding Yuan WANG ; Song Lin GAO ; Nan Lin HU ; Yi Ran SI ; Fang Chao ZHENG ; Jie JU ; Zheng WANG ; Peng YUAN
Chinese Journal of Oncology 2023;45(11):948-954
Objectives: To find the prognostic factors related to early triple-negative breast cancer to optimize the therapeutic strategies, and explore the influence of programmed cell death ligand-1(PD-L1)expression in early triple-negative breast cancer on its prognosis, so as to provide support for clinical treatment decisions. Methods: Early triple-negative breast cancer patients treated at the National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences during 1st June, 2009 and 31st Oct, 2015 were enrolled in this study. All the clinicopathological data of patients were collected, and the paraffin sections of the surgical specimens were stained with estrogen receptor, progesterone receptor, human epidermal growth factor receptor-2, secreted protein acidic and rich in cysteine (SPARC), androgen receptor, PD-L1 and other antibodies by the immunohistochemical method. Kaplan-Meier survival and Cox regression curves were used for survival analysis of relevant clinical and pathological results and nomogram survival prediction models were established to explore the influence of relevant factors on the prognosis. Results: A total of 205 patients with triple-negative breast cancer were enrolled. Ninety patients (43.9%) were PD-L1 positive. The median follow-up time was 63 months. Thirty-seven patients were relapsed or recurrent and 16 patients were dead. The 5-year disease-free survival (DFS) rate and overall survival (OS) rate were 86.1% (95% CI: 81.4%-90.8%) and 93.6% (95% CI: 91.0%-97.6%), respectively, in the general population. Univariate Cox regression analysis showed that PD-L1 expression and lymph node metastasis were correlated with DFS and OS (P<0.05). In multivariate analysis, PD-L1 expression was an independent influencing factor of DFS, with PD-L1 positive patients possessing a significant survival benefit in DFS (HR=0.31, 95% CI: 0.13-0.73). Lymph node metastasis was an independent influencing factor of OS, and OS was significantly shortened in patients with positive lymph node metastasis (HR=3.24, 95% CI: 1.15-9.17). PD-L1, lymph node metastasis, menopausal status, Ki-67 index and adjuvant chemotherapy regimen were included to establish the 1- and 3-year DFS and OS nomogram prediction models, resulting in C indices of 0.698 and 0.748, respectively. Conclusions: PD-L1 expression is a predictive biomarker of good prognostic factor in triple-negative breast cancer patients. DFS is significantly prolonged in PD-L1 positive patients and OS also shows a prolongation trend. The nomogram prognosis prediction models have reference values for adjuvant chemotherapy in this patient group.
Humans
;
Female
;
Lymphatic Metastasis
;
B7-H1 Antigen/metabolism*
;
Triple Negative Breast Neoplasms/pathology*
;
Breast Neoplasms
;
Osteonectin/therapeutic use*
;
Prognosis
6.Predictive Value of Peripheral Blood Biomarkers in the Treatment of Lung Cancer Patients with Anti PD-1 Immunotherapy.
Shu SU ; Xin LV ; Liang QI ; Min WEI ; Baorui LIU ; Lifeng WANG
Chinese Journal of Lung Cancer 2024;26(12):901-909
BACKGROUND:
The application of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) antibodies has greatly improved the clinical outcomes of lung cancer patients. Here, we retrospectively analyzed the efficacy of PD-1 antibody therapy in locally advanced non-surgical or metastatic lung cancer patients, and preliminarily explored the correlation between peripheral blood biomarkers and clinical responses.
METHODS:
We conducted a single center study that included 61 IIIA-IV lung cancer patients who received PD-1 antibody treatment from March 2020 to December 2021, and collected the medical record data on PD-1 antibody first-line or second-line treatment. The levels of multiple Th1 and Th2 cytokines in the patient's peripheral blood serum, as well as the phenotype of peripheral blood T cells, were detected and analyzed.
RESULTS:
All the patients completed at least 2 cycles of PD-1 monoclonal antibody treatment. Among them, 42 patients (68.9%) achieved partial response (PR); 7 patients (11.5%) had stable disease (SD); and 12 patients (19.7%) had progressive disease (PD). The levels of peripheral blood interferon gamma (IFN-γ) (P=0.023), tumor necrosis factor α (TNF-α) (P=0.007) and interleukin 5 (IL-5) (P=0.002) before treatment were higher in patients of the disease control rate (DCR) (PR+SD) group than in the PD group. In addition, the decrease in absolute peripheral blood lymphocyte count after PD-1 antibody treatment was associated with disease progression (P=0.023). Moreover, the levels of IL-5 (P=0.0027) and IL-10 (P=0.0208) in the blood serum after immunotherapy were significantly increased compared to baseline.
CONCLUSIONS
Peripheral blood serum IFN-γ, TNF-α and IL-5 in lung cancer patients have certain roles in predicting the clinical efficacy of anti-PD-1 therapy. The decrease in absolute peripheral blood lymphocyte count in lung cancer patients is related to disease progression, but large-scale prospective studies are needed to further elucidate the value of these biomarkers.
Humans
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Lung Neoplasms/metabolism*
;
Interleukin-5/therapeutic use*
;
Tumor Necrosis Factor-alpha/therapeutic use*
;
Retrospective Studies
;
Programmed Cell Death 1 Receptor
;
Biomarkers
;
Immunotherapy
;
Disease Progression
;
B7-H1 Antigen
7.Immunotherapy with PD-1 and PD-L1 inhibitors for prostate cancer.
National Journal of Andrology 2020;26(10):944-948
Prostate cancer (PCa) has become one of the common malignant diseases in elderly men, and its incidence is increasing year by year. Apart from surgery, radiotherapy and chemotherapy, immunotherapy, as with the programmed death receptor-1 (PD-1) or the programmed death ligand-1 (PD-L1) inhibitor, is a most promising new strategy for the treatment of PCa. PD-1 and PD-L1 inhibitors restore the activity of T cells by blocking the PD-1/PD-L1 signaling pathway in tumor cells, reverse the mechanism of tumor immune escape, recover the immune system and directly kill tumor cells. This review focuses on the current progress in the studies of PD-1 and PD-L1 inhibitors in the treatment of PCa.
B7-H1 Antigen/antagonists & inhibitors*
;
Humans
;
Immune Checkpoint Inhibitors/therapeutic use*
;
Immunotherapy
;
Male
;
Programmed Cell Death 1 Receptor/antagonists & inhibitors*
;
Prostatic Neoplasms/drug therapy*
;
Signal Transduction
8.Research Progress of Anti-PD-1/PD-L1 Therapy for Non-small Cell Lung Cancer with EGFR Mutation.
Chinese Journal of Lung Cancer 2022;25(10):742-749
The use of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is the first line treatment for EGFR-mutant advanced non-small cell lung cancer (NSCLC), but drug resistance will be acquired within 1-2 years, and the following treatment efficacy is poor. The invention of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors has dramatically changed the situation of tumor treatment. PD-1/PD-L1 inhibitors are less effective in patients with NSCLC harboring EGFR mutation. It is a challenge to make patients with EGFR-mutated advanced NSCLC benefit from anti-PD-1/PD-L1 therapy. In this paper, the research progress on the impact of EGFR mutation on the immune status of NSCLC and related clinical studies in recent 5 years are reviewed.
.
Humans
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Carcinoma, Non-Small-Cell Lung/pathology*
;
B7-H1 Antigen/metabolism*
;
Lung Neoplasms/pathology*
;
Immune Checkpoint Inhibitors
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Ligands
;
Mutation
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ErbB Receptors/metabolism*
;
Protein Kinase Inhibitors/therapeutic use*
9.Application of Immune Checkpoint Inhibitors in EGFR Mutant Advanced Non-small Cell Lung Cancer.
Yujun ZHENG ; Wei JIANG ; Jing LI ; Lulu DAI ; Dongyan CHEN ; Yanjun LI ; Lei HUANG ; Mingji WANG
Chinese Journal of Lung Cancer 2022;25(9):671-677
In recent years, immune checkpoint inhibitors (ICIs) have greatly improved the survival rate of non-small cell lung cancer (NSCLC) patients without driver mutation. Compared with wild-type tumors, tumors with epidermal growth factor receptor (EGFR) mutations have greater heterogeneity in immune microenvironment characteristics such as programmed cell death ligand 1 (PD-L1) and tumor mutational burden (TMB). Whether ICIs is suitable for NSCLC patients with EGFR mutation has been controversial. Clinical studies have shown that immunomonotherapy has no significant effect on patients with EGFR mutant NSCLC. ICIs combined with chemotherapy and antiangiogenic drugs show good survival benefits. This paper overviews the clinical research and related mechanism of ICIs single drug or combination therapy inadvanced NSCLC patients with EGFR mutation.
.
B7-H1 Antigen/metabolism*
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Carcinoma, Non-Small-Cell Lung/pathology*
;
ErbB Receptors/metabolism*
;
Humans
;
Immune Checkpoint Inhibitors/therapeutic use*
;
Ligands
;
Lung Neoplasms/pathology*
;
Mutation
;
Tumor Microenvironment
10.Assessment of the safety and efficacy of combination chemotherapy and PD-1/PD-L1 inhibitor treatment of breast cancer: A meta-analysis.
Da QIAN ; Yuhao XU ; Yihao WU ; Jie QIU ; Weimin HONG ; Xuli MENG
Chinese Medical Journal 2023;136(14):1663-1670
BACKGROUND:
As the efficacy of programmed cell death-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors combined with chemotherapy in curing breast cancer is still controversial, this meta-analysis compares the efficacy and safety of PD-1/PD-L1 inhibitors combined with chemotherapy and chemotherapy alone in the treatment of breast cancer, which provides guidance for the clinical treatment.
METHODS:
Relevant studies published as of April 2022 in the various databases including EMBASE, PubMed, and Cochrane Library were selected. Randomized controlled trials (RCTs) in which control patients underwent chemotherapy alone and experimental group patients underwent combination chemotherapy and PD-1/PD-L1 inhibitor treatment were included in this investigation. Investigations without complete information, researches from which information could not be extracted, duplicate articles, animal studies, review articles, and systematic reviews were excluded. STATA 15.1 was employed for all statistical analyses.
RESULTS:
In total, eight eligible studies were identified, revealing that combination chemotherapy and PD-1/PD-L1 inhibitor treatment was linked to significant increases in progression-free survival (PFS) relative to chemotherapy alone (hazard ratio [HR] = 0.83, 95% confidence interval [CI]: 0.70-0.99, P = 0.032) but not overall survival (HR = 0.92, 95% CI: 0.80-1.06, P = 0.273). Pooled adverse event rates were also increased within the group of combination treatment relative to the chemotherapy group (risk ratio [RR] = 1.08, 95% CI: 1.03-1.14, P = 0.002). Specifically, nausea rates were lesser within the group of combination treatment relative to the group of chemotherapy (RR = 0.48, 95% CI: 0.25-0.92, P = 0.026). Subgroup analyses indicated that the PFS of patients who underwent combination atezolizumab or pembrolizumab and chemotherapy treatment were substantially longer than those of patients who underwent chemotherapy alone (HR = 0.79, 95% CI: 0.69-0.89, P ≤0.001; HR = 0.79, 95% CI: 0.67-0.92, P = 0.002).
CONCLUSIONS
The pooled results suggest that combination chemotherapy and PD-1/PD-L1 inhibitor treatment approaches help prolong PFS in breast cancer patients, but have no statistically significant effect on overall survival (OS). Additionally, combination therapy can significantly improve complete response rate (CRR) compared with chemotherapy alone. However, combination therapy was associated with greater rates of adverse events.
Humans
;
B7-H1 Antigen/antagonists & inhibitors*
;
Drug Therapy, Combination
;
Immune Checkpoint Inhibitors/therapeutic use*
;
Programmed Cell Death 1 Receptor/antagonists & inhibitors*
;
Breast Neoplasms/drug therapy*