Dataset Information

[Progress in Clinical Researches of PD-1/PD-L1 Checkpoint Inhibitor for Non-small Cell Lung Cancer].

ABSTRACT: Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. In recent years, immunotherapy has developed rapidly. Immune checkpoint inhibitors, especially programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors have made a breakthrough in the treatment of NSCLC and changed the treatment pattern for NSCLC. Immunological checkpoint inhibitors targeting PD-1/PD-L1 are beneficial to patients, both in the first-line and second-line treatment of advanced NSCLC, in the adjuvant treatment of locally-advanced NSCLC, and in the neoadjuvant therapy of early NSCLC, which show an important role in the comprehensive treatment of NSCLC. This article reviews the clinical research progress of immunological checkpoint inhibitors targeting PD-1/PD-L1 in NSCLC.?.

SUBMITTER: Wu S

PROVIDER: S-EPMC6712270 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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[Progress in Clinical Researches of PD-1/PD-L1 Checkpoint Inhibitor for Non-small Cell Lung Cancer].

Wu Sixuan S Hu Chunhong C Wu Fang F Wu Yuanqiang Y Liu Ping P

Zhongguo fei ai za zhi = Chinese journal of lung cancer 20190701 7

Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. In recent years, immunotherapy has developed rapidly. Immune checkpoint inhibitors, especially programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors have made a breakthrough in the treatment of NSCLC and changed the treatment pattern for NSCLC. Immunological checkpoint inhibitors targeting PD-1/PD-L1 are beneficial to patients, both in the first-line and second-line treatment of advanced NSCL ...[more]

PMID: 31315783

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Project description:BackgroundMany clinical studies have shown that patients with non-small cell lung carcinoma (NSCLC) can benefit from immune checkpoint inhibitor (ICI) therapy; however, PD-L1 and tumor mutation burden (TMB), which are recommended by the NCCN guidelines, are still insufficient in predicting the response to and prognosis of immunotherapy. Given the widespread use of ICIs, it is important to find biomarkers that can predict immunotherapy outcomes in NSCLC patients, and the exploration of additional effective biomarkers for ICI therapy is urgently needed.MethodsA total of 33 stage II-IV NSCLC patients were included in this study. We analyzed immune markers in biopsy and surgical tissue resected from these patients before treatment with ICIs. We examined the infiltration of immune cells and expression of PD-L1 in immune cells using fluorescent multiplex immunohistochemistry (mIHC) stained with CD8/CD68/CD163/PD-L1 antibodies.ResultsIn this cohort, we observed that the levels of CD8+ T cells, CD8+PD-L1+ T cells, and CD68+CD163+ M2 macrophages in the total region were independent prognostic factors for progression-free survival (PFS) in NSCLC patients treated with ICIs (HR=0.04, P=0.013; HR=17.70, P=0.026; and HR=17.88, P=0.011, respectively). High infiltration of CD8+ T cells and low infiltration of CD8+PD-L1+ T cells throughout the region were correlated with prolonged PFS (P=0.016 and P=0.02, respectively). No statistically significant difference was observed for CD68+CD163+ M2 macrophages. The joint parameters CD8+ high/CD8+PD-L1+ low, CD8+ high/CD68+CD163+ low and CD8+PD-L1+ low/CD68+CD163+ low predicted better PFS than other joint parameters (P<0.01, P<0.01, and P<0.001, respectively), and they also demonstrated stronger stratification than single biomarkers. The response rate of patients with high infiltration of CD8+ T cells was significantly higher than that of those with low infiltration (P<0.01), and the joint parameters CD8+/CD8+PD-L1+ and CD8+/CD68+CD163+ also demonstrated stronger stratification than single biomarkers.ConclusionsThis retrospective study identified the predictive value of CD8+PD-L1+ T cells, CD8+ T cells, and CD68+CD163+ M2 macrophages in NSCLC patients who received ICIs. Interestingly, our results indicate that the evaluation of joint parameters has certain significance in guiding ICI treatment in NSCLC patients.

Project description:IntroductionThe proportion of older patients diagnosed with advanced-stage non-small cell lung cancer (NSCLC) has been increasing. Immune checkpoint inhibitor (ICI) monotherapy (MONO) and combination therapy of ICI and chemotherapy (COMBO) are standard treatments for patients with NSCLC and programmed cell death ligand-1 (PD-L1) tumor proportion scores (TPS) ≥ 50%. However, evidence from the clinical trials specifically for older patients is limited. Thus, it is unclear which older patients benefit more from COMBO than MONO.MethodsWe retrospectively analyzed 199 older NSCLC patients of Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1 and PD-L1 TPS ≥ 50% who were treated with MONO or COMBO. We analyzed the association between treatment outcomes and baseline patient characteristics in each group, using propensity score matching.ResultsOf the 199 patients, 131 received MONO, and 68 received COMBO. The median overall survival (OS; MONO: 25.2 vs. COMBO: 42.2 months, P = 0.116) and median progression-free survival (PFS; 10.9 vs. 11.8 months, P = 0.231) did not significantly differ between MONO and COMBO group. In the MONO group, OS was significantly shorter in patients without smoking history compared to those with smoking history [HR for smoking history against non-smoking history: 0.36 (95% CI: 0.16-0.78), P = 0.010]. In the COMBO group, OS was significantly shorter in patients with PS 1 than those with PS 0 [HR for PS 0 against PS 1: 3.84 (95% CI: 1.44-10.20), P = 0.007] and for patients with squamous cell carcinoma (SQ) compared to non-squamous cell carcinoma (non-SQ) [HR for SQ against non-SQ: 0.17 (95% CI: 0.06-0.44), P < 0.001]. For patients with ECOG PS 0 (OS: 26.1 months vs. not reached, P = 0.0031, PFS: 6.5 vs. 21.7 months, P = 0.0436) or non-SQ (OS: 23.8 months vs. not reached, P = 0.0038, PFS: 10.9 vs. 17.3 months, P = 0.0383), PFS and OS were significantly longer in the COMBO group.ConclusionsECOG PS and histological type should be considered when choosing MONO or COMBO treatment in older patients with NSCLC and PD-L1 TPS ≥ 50%.

Dataset Information

[Progress in Clinical Researches of PD-1/PD-L1 Checkpoint Inhibitor for Non-small Cell Lung Cancer].

Publications

[Progress in Clinical Researches of PD-1/PD-L1 Checkpoint Inhibitor for Non-small Cell Lung Cancer].

Similar Datasets

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