Prognostic Value Of PD-L1 Expression Research Articles

Prognostic value of PD-L1expression in patients with anal cancer: a meta-analysis.

Background: The present meta-analysis was performed to evaluate theprognostic and clinicopathological significance of PD-L1in anal cancer (AC). Methods: Hazard ratios (HRs) and 95%CIsregarding overall survival (OS) and progression-free survival (PFS) were calculated based on PD-L1 levels. Results: According to the combined data, PD-L1 showed no significant relationship with OS (HR=0.76; 95%CI=0.35-1.67; p=0.502) or PFS (HR=0.88; 95%CI=0.35-2.33; p=0.789) in patients with AC. Based on subgroup analysis, PD-L1 overexpression significantly predicted prolonged OS (HR=0.38; 95%CI=0.17-0.84; p=0.017) in tumor node metastasis stages I-III and inferior PFS (HR=2.73; 95%CI=1.32-5.65; p=0.007) inpatients with stage I-IV AC. Conclusion: PD-L1 level assessed by immunohistochemistry did not significantly predict survival outcomes inAC cases.

Impact of PD-L1 expression on survival in patients with unresectable/recurrent gastric cancer receiving first-line chemotherapy without immune checkpoint inhibitors.

391 Background: Although high PD-L1 expression predicts a favorable response of advanced solid tumors to immune checkpoint inhibitors (ICIs), its impact on survival in patients with unresectable/recurrent gastric cancer (GC) has remained unclear. We investigated the prognostic value of PD-L1 expression for survival in unresectable/recurrent GC patients receiving first-line chemotherapy without ICIs. Methods: JCOG1013, a phase 3 randomized trial, demonstrated the addition of docetaxel to cisplatin and S-1 as first-line chemotherapy was of no benefit to patients with unresectable/recurrent GC (N=741) either for overall survival (OS) or progression-free survival (PFS). Tumor specimens prior to chemotherapy were collected for assessing PD-L1 expression for this ancillary study. PD-L1 expression was determined using immunohistochemistry (Dako, 28-8 pharmDx) and used to derive the PD-L1 combined positive score (CPS) and PD-L1 tumor proportion score (TPS). As with the CheckMate 649 study, the cutoff values for PD-L1 CPS and PD-L1 TPS were set at 5 and 1%, respectively. Multivariable analyses were performed using Cox proportional hazard models to evaluate the prognostic significance of PD-L1 CPS and PD-L1 TPS as predictors of OS and PFS. All p values were 2-sided; values <0.05 were considered statistically significant. Results: We analyzed 427 patients with unresectable/recurrent GC. The prevalence of PD-L1 CPS≥5, and PD-L1 TPS≥1% was 33% and 24%, respectively. There was no significant difference in OS and PFS between the PD-L1 CPS ≥5 group and the PD-L1 CPS <5 group (Table). The PD-L1 TPS ≥1% group had superior OS and PFS compared to the PD-L1 TPS <1% group (Table). In multivariable analyses for OS, PD-L1 TPS ≥1% was a significant favorable prognostic factor (hazard ratio (HR) = 0.64 [95% CI: 0.50–0.83], p<0.001), but PD-L1 CPS≥5 was not (HR = 0.82 [95% CI: 0.65–1.02], p = 0.073). In multivariable analyses for PFS, PD-L1 TPS ≥1% was a significant favorable prognostic factor (HR = 0.67 [95% CI: 0.52–0.84], p<0.001), but PD-L1 CPS≥5 was not (HR = 0.83 [95% CI: 0.67–1.03], p = 0.090). Conclusions: PD-L1 TPS≥1% is significantly correlated with longer OS and PFS in patients with unresectable/recurrent GC receiving first-line chemotherapy without ICIs. PD-L1 TPS should be considered as a stratification factor in randomized clinical trials for unresectable/recurrent GC. Clinical trial information: UMIN000007652 . [Table: see text]

Prevalence and prognostic value of PD-L1 expression and tumor mutational burden in persistent, recurrent, or metastatic cervical cancer

Prevalence and prognostic value of PD-L1 expression and tumor mutational burden in persistent, recurrent, or metastatic cervical cancer

Prognostic value of PD-1, PD-L1 and PD-L2 deserves attention in head and neck cancer.

Head and neck cancer has high heterogeneity with poor prognosis, and emerging researches have been focusing on the prognostic markers of head and neck cancer. PD-L1 expression is an important basis for strategies of immunosuppressive treatment, but whether it has prognostic value is still controversial. Although meta-analysis on PD-L1 expression versus head and neck cancer prognosis has been performed, the conclusions are controversial. Since PD-L1 and PD-L2 are two receptors for PD-1, here we summarize and analyze the different prognostic values of PD-1, PD-L1, and PD-L2 in head and neck cancer in the context of different cell types, tissue localization and protein forms. We propose that for head and neck cancer, the risk warning value of PD-1/PD-L1 expression in precancerous lesions is worthy of attention, and the prognostic value of PD-L1 expression at different subcellular levels as well as the judgment convenience of prognostic value of PD-1, PD-L1, PD-L2 should be fully considered. The PD-L1 evaluation systems established based on immune checkpoint inhibitors (ICIs) are not fully suitable for the evaluation of PD-L1 prognosis in head and neck cancer. It is necessary to establish a new PD-L1 evaluation system based on the prognosis for further explorations. The prognostic value of PD-L1, PD-L2 expression in head and neck cancer may be different for early-stage and late-stage samples, and further stratification is required.

EP07.01-011 Integrating PD-L1 Expression to the CALGB Prognostic Scoring System in Malignant Pleural Mesothelioma

Programmed death ligand-1 (PD-L1) expression is a predictive biomarker guiding treatment decisions with immunotherapy in lung cancer patients, but its role in malignant pleural mesothelioma (MPM) is unclear. However, evidence suggests that higher PDL-1 expression correlates with worse survival outcomes. The Cancer and Leukemia Group B (CALGB) prognostic scoring system is widely used to define prognosis in MPM. This study aims to assess the prognostic value of PDL-1 expression integrating it into the CALGB scoring system.

CISH Expression Is Associated with Metastasis-Free Interval in Triple-Negative Breast Cancer and Refines the Prognostic Value of PDL1 Expression.

Simple SummaryCISH is a member of the suppressors of cytokine signaling (SOCS) family of proteins and an important negative regulator of T cells and NK cells signaling and function. In this study, analyzing 1936 triple-negative breast cancer (TNBC) clinical samples, we highlighted correlation between CISH expression and tumor features. We demonstrated that high CISH upregulation was associated with better metastasis-free interval, especially when PDL1 was also upregulated. Moreover, we showed that the two-gene model (CISH and PDL1) provided more prognostic information than each gene alone and maintained its prognostic value in multivariate analysis. Such prognostic synergy between CISH and PDL1 expressions might reinforce the therapeutic relevance of co-targeting TNBC by a combination of CISH inhibition with an immune checkpoint inhibitor blocking the PD1/PDL1 axis.Strategies are being explored to increase the efficiency of immune checkpoint inhibitors (ICIs) targeting PD1/PDL1 in triple-negative breast cancer (TNBC), including combination with therapies inhibiting intracellular immune checkpoints such as CISH (Cytokine-induced SH2 protein). Correlation between CISH expression and TNBC features is unknown. We retrospectively analyzed CISH expression in 1936 clinical TNBC samples and searched for correlations with clinical variables, including metastasis-free interval (MFI). Among TNBCs, 44% were identified as “CISH-up” and 56% “CISH-down”. High expression was associated with pathological axillary lymph node involvement, more adjuvant chemotherapy, and Lehmann’s immunomodulatory and luminal AR subtypes. The “CISH-up” class showed longer 5-year MFI (72%) than the “CISH-down” class (60%; p = 2.8 × 10−2). CISH upregulation was associated with activation of IFNα and IFNγ pathways, antitumor cytotoxic immune response, and signatures predictive for ICI response. When CISH and PDL1 were upregulated together, the 5-year MFI was 81% versus 52% when not upregulated (p = 6.21 × 10−6). The two-gene model provided more prognostic information than each gene alone and maintained its prognostic value in multivariate analysis. CISH expression is associated with longer MFI in TNBC and refines the prognostic value of PDL1 expression. Such observation might reinforce the therapeutic relevance of combining CISH inhibition with an anti-PD1/PDL1 ICI.

Prognostic value of PD-L1 expression combined with hypoxia-associated immunosuppression in hepatocellular carcinoma.

Background: Hypoxia and immunosuppression are two properties of cancer. This study intends to establish the potential relationship between these two hallmarks in hepatocellular carcinoma (HCC). Materials & methods: A bioinformatics analysis of data obtained from the Cancer Genome Atlas and a retrospective single-center analysis based on a tissue microarray were utilized in this study. Results: We identified a hypoxia-high subtype of patients with immunosuppressive HCC which represented a poor prognosis in the Cancer Genome Atlas cohort. Immunohistochemical analysis of the tissue microarray showed that tumor PD-L1 expression was positively linked to HIF-1α expression, pro-tumor immunocyte infiltration and poor survival in HCC patients. Conclusion: This study provides evidence supporting the correlation between hypoxic signals and immunosuppression in HCC; the combined use of them might improve survival prediction and act as a potential predictor for PD-1/PD-L1 therapy.

PD-L1 and survival in oral cavity squamous cell carcinoma

Relevance. Prognostic value of PD-L1 expression in oral cavity squamous cell carcinoma (OCSCC) and its effect on survival is still controversial. It should be to determine the prognostic role of PD-L1 expression on tumor and immune cells of OCSCC and assess their effect on overall survival (OS) and progression-free survival (PFS).Materials and methods. A prospective study included 145 patients, first diagnosed with OCSCC. PD-L1 expression on tumor and immune cells, infiltrating tumor and its microenvironment, was assessed in all tumor samples by IHC, CPS was calculated. Cut-off values were determined by ROC analysis for identification of PD-L1 expression effect on OS and PFS.Results. Most patients with oral mucosa squamous cell carcinoma showed positive expression of PD-L1 on tumor (77.2%) and immune cells (92.4%). The median PD-L1 expression on tumor cells was 13.5% [1.0-40.0], the median PD-L1 expression on immune cells was 5.0% [1.0-11.0], and the median CPS – 18.0 [3.0-7.8]. Univariate and multivariate analyses revealed a significant negative effect of PD-L1 expression on immune cells ≤ 7% on OS (HR 0.66; 95% CI 0.45-0.93; p = 0.0498); PD-L1 expression in tumor cells ≤ 15% (HR 0.65; 95% CI 0.43-0.98; p = 0.0416) and CPS ≤ 21 (HR 0.62; 95% CI 0.44-0.92; p = 0.0183) for PFS. PD-L1 expression in tumor cells ≤ 6% (HR 0.71; 95% CI 0.47-1.08; p = 0.1096) and CPS ≤ 7 (RR 0.67; 95% CI 0.44-1.01; p = 0.0575) had a confident tendency to negative impact on OS.Conclusion. Positive PD-L1 expression in tumor and immune cells as well as CPS are effective additional factors in the prognosis of the disease course, OS and PFS in patients with OCSCC.

PD-L1 Expression in 65 Conjunctival Melanomas and Its Association with Clinical Outcome.

Conjunctival melanoma (CM) iss a rare and aggressive tumour that is increasing in frequency. The prognostic value of PD-L1 expression, alone or in combination with CD8 and PD-1 expression and the BRAF and NRAS status, has not been determined in CM to date. We evaluated the expression of PD-L1, CD8, PD-1 in CM and investigated whether there was an association between the expression of these markers and the BRAF and NRAS molecular profile as well as some clinico-pathological criteria. A total of sixty-five CM were assessed for PD-L1, PD-1, and CD8 expression by immunohistochemistry (IHC) and for BRAF and NRAS genomic alterations using molecular biology techniques and anti-BRAF and anti-NRAS antibodies. PD-L1 expression in tumour cells (TC) was very low or absent but detected in tumour-infiltrating immune cells (IC). A correlation was observed between the expression of PD-L1, CD8, and PD-1 in IC. No correlation between PD-L1 expression (in tumour and/or immune cells) and BRAF or NRAS mutations was observed. PD-L1 expression in IC correlated with a higher pTNM stage and PD-L1 expression in TC with worse disease-specific survival. PD-L1 expression is a potential prognostic biomarker that correlates with poor prognosis in CM patients.

Prognostic value of PD-L1 expression in patients with unresectable stage III non-small cell lung cancer treated with chemoradiotherapy

BackgroundExpression of PD-L1 is the most investigated predictor of benefit from immune checkpoint blockade in advanced NSCLC but little is known about the association of PD-L1 expression and clinicopathological parameters of patients with unresectable stage III NSCLC.MethodsNational registry data was searched for medical records of consecutive inoperable stage III NSCLC patients treated with ChT and RT from January 2012 to December 2017. Totally 249 patients were identified that met inclusion criteria and of those 117 patients had sufficient tissue for PD-L1 immunohistochemical staining.ResultsEighty patients (68.4%) expressed PD-L1 of ≥ 1% and 29.9% of more than 50%. Median PFS was 15.9 months in PD-L1 negative patients and 16.1 months in patients with PD-L1 expression ≥ 1% (p = 0.696). Median OS in PD-L1 negative patients was 29.9 months compared to 28.5 months in patients with PD-L1 expression ≥ % (p = 0.888). There was no difference in median OS in patients with high PD-L1 expression (≥ 50%) with 29.8 months compared to 29.9 months in those with low (1–49%) or no PD-L1 expression (p = 0.694). We found that patients who received a total dose of 60 Gy or more had significantly better median OS (32 months vs. 17.5 months, p < 0.001) as well as patients with PS 0 (33.2 vs. 20.3 months, p = 0.005).ConclusionsIn our patients PD-L1 expression had no prognostic value regarding PFS and OS. Patients with good performance status and those who received a total radiation dose of more than 60 Gy had significantly better mOS.

Abstract LB-153: Prognostic value of PD-L1 expression on tumor-infiltrating immune cells in renal cell carcinoma (ARCHERY study)

Abstract Background: The correlation between PD-L1 expression on tumor-infiltrating immune cells and prognosis in renal cell carcinoma (RCC) has been reported in several studies. Methods: A multicenter retrospective study was carried out to investigate the prognostic value of PD-L1 expression (by the VENTANA SP142 immune cell [IC] scoring method) in primary RCC tumors among patients administered systemic therapy for recurrent or metastatic RCC. The primary endpoint was overall survival (OS), defined as the time from the initiation of first-line treatment to the date of death from any cause. The difference in OS between patients of positive PD-L1 status (IC ≥1%) and those of negative status was compared using a stratified log-rank test at a two-sided level of 0.1, stratified by MSKCC risk and liver metastases. Stratified hazard ratio (HR) and its 90% confidence interval (CI) was estimated by the Cox proportional hazard model. An unstratified analysis and an analysis adjusted by propensity score weighting (PSW) were also conducted. Results: We examined 777 RCC surgical specimens, 770 of which were included for primary analysis (7 were excluded owing to indeterminate PD-L1 status). PD-L1 positive was observed in 315 (40.9%). Immune phenotype that describe the level of T-cell presence and activity within the tumor microenvironment differed between PD-L1-positive vs. -negative groups: Excluded (74.3% vs. 31.6%), Inflamed (16.5% vs. 1.5%), and Desert (9.2% vs. 66.8%). PD-L1-positive status was more common in patients with higher clinical stage, higher Fuhrman grade, and presence of sarcomatoid component. A higher proportion of PD-L1-positive patients had poor prognostic features at the start of first-line therapy: 17.5% vs. 7.3% with ‘poor' MSKCC risk; 29.2% vs. 14.9% with ‘poor' IMDC risk. In line with this, fewer PD-L1-positive patients had good prognostic features at the start of first-line therapy: 11.4% vs. 29.7% with ‘favorable' MSKCC risk; 10.8% vs. 26.2% with ‘favorable' IMDC risk.The median OS in PD-L1-positive vs. -negative patients was 30.9 months (95%CI: 25.5-35.7) vs. 37.5 months (95%CI: 34.0-42.6). The stratified HR was 1.04 (90%CI: 0.89-1.22, P=0.65), the unstratified HR was 1.21 (90%CI: 1.04-1.40), and the PSW-adjusted HR was 0.99. Subgroup analysis based on MSKCC risk at the start of first-line therapy revealed that there was no significant difference in mOS based on PD-L1-positive vs. -negative status for ‘favorable' (58.6 vs. 59.8 months; HR: 0.92; 95%CI: 0.54-1.56), ‘intermediate' (31.6 vs. 33.5; HR: 1.06; 95%CI: 0.85-1.32) or ‘poor' (6.6 vs 12.8.; HR: 0.89; 95%CI: 0.55-1.43) categories. Conclusion: This study suggested that PD-L1 status on tumor-infiltrating immune cells was not an independent prognostic factor in recurrent or metastatic RCC patients, although positive PD-L1 status was associated with poor prognostic factors. Citation Format: Hirotsugu Uemura, Motohide Uemura, Naoto Sassa, Noboru Nakaigawa, Katsunori Tatsugami, Kenichi Harada, Toshinari Yamasaki, Nobuaki Matsubara, Tamaki Fukuyama, Takuya Yoshimoto, Yuki Nakagawa, Mototsugu Oya, Nobuo Shinohara, Toyonori Tsuzuki. Prognostic value of PD-L1 expression on tumor-infiltrating immune cells in renal cell carcinoma (ARCHERY study) [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-153.

A pooled analysis of the prognostic value of PD-L1 in melanoma: evidence from 1062 patients.

BackgroundProgrammed death-ligand 1 (PD-L1) was the first identified ligand of programmed death-1 (PD-1). PD-1/PD-L1 interactions inhibit T cell-mediated immune responses, limit cytokine production, and promote tumor immune escape. Recently, many studies have investigated the prognostic value of PD-L1 expression in patients with melanoma. However, the results of these analyses remain a subject of debate. We have therefore carried out a meta-analysis to identify the prognostic role of PD-L1 in melanoma.MethodsA thorough medical literature search was performed in the databases PubMed, Web of Science, and Embase until October 2019. The pooled hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated to evaluate the correlation between PD-L1 overexpression and prognosis. Publication bias was evaluated using Begg’s test and Egger’s test.ResultsThirteen articles with 1062 enrolled patients were included in this meta-analysis. High PD-L1 expression did not correlate with overall survival (OS) (HR = 0.93, 95% CI 0.57–1.52, P = 0.781) or progression-free survival (PFS) (HR = 0.82, 95% CI 0.43–1.54, P = 0.535). However, PD-L1 overexpression correlated with the absence of lymph node (LN) metastasis (OR = 0.46, 95% CI 0.22–0.95, P = 0.036). Further, there was no significant relationship between PD-L1 expression and sex (OR = 1.29, 95% CI 0.90–1.84, P = 0.159), age (OR = 0.90, 95% CI 0.51–1.57, P = 0.708), or Eastern Cooperative Oncology Group Performance Status (OR = 0.55, 95% CI 0.06–4.83, P = 0.592).ConclusionsThis meta-analysis suggested that PD-L1 expression did not predict an inferior prognosis in patients with melanoma. However, high PD-L1 expression was associated with absence of LN metastasis in such patients.

Prognostic value of PD-L1 expression on tumor cells combined with CD8+ TIL density in patients with locally advanced non-small cell lung cancer treated with concurrent chemoradiotherapy

Background/aimmmune checkpoint inhibition (CPI) has an increasing impact in the multimodal treatment of locally advanced non-small cell lung cancer (LA-NSCLC). Increasing evidence suggests treatment outcome depending on tumor cell PD-L1 expression. The purpose of this retrospective study was to investigate the prognostic value of PD-L1 expression on tumor cells in combination with CD8+ tumor stroma-infiltrating lymphocyte (TIL) density in inoperable LA-NSCLC treated with concurrent chemoradiotherapy (CRT).Patients and methodWe retrospectively assessed clinical characteristics and initial tumor biopsy samples of 31 inoperable LA-NSCLC patients treated with concurrent CRT. Prognostic impact of tumor cell PD-L1 expression (0% versus ≥1%) and CD8+ TIL density (0–40% vs. 41–100%) for local control, progression-free (PFS) and overall survival (OS) as well as correlations with clinicopathological features were evaluated.ResultsMedian OS was 14 months (range: 3–167 months). The OS rates at 1- and 2 years were 68 and 20%. Local control of the entire cohort at 1 and 2 years were 74 and 61%. Median PFS, 1-year and 2-year PFS were 13 ± 1.4 months, 58 and 19%. PD-L1 expression < 1% on tumor cells was associated with improved OS, PFS and local control in patients treated with concurrent CRT. Univariate analysis showed a trend towards improved OS and local control in patients with low CD8+ TIL density. Evaluation of Tumor Immunity in the MicroEnvironment (TIME) appears to be an independent prognostic factor for local control, PFS and OS. The longest and shortest OS were achieved in patients with type I (PD-L1neg/CD8low) and type IV (PD-L1pos/CD8low) tumors (median OS: 57 ± 37 vs. 10 ± 5 months, p = 0.05), respectively.ConclusionAssessment of PD-L1 expression on tumor cells in combination with CD8+ TIL density can be a predictive biomarker in patients with inoperable LA-NSCLC treated with concurrent CRT.

The Prognostic Value of PD-L1 Expression in Triple-Negative Breast Cancer: A Cohort Study and Systematic Literature Review

The Prognostic Value of PD-L1 Expression in Triple-Negative Breast Cancer: A Cohort Study and Systematic Literature Review

SUPREME-HN: a retrospective biomarker study assessing the prognostic value of PD-L1 expression in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck

BackgroundProgrammed cell death ligand-1 (PD-L1) expression on tumor cells (TCs) is associated with improved survival in patients with head and neck squamous cell carcinoma (HNSCC) treated with immunotherapy, although its role as a prognostic factor is controversial. This study investigates whether tumoral expression of PD-L1 is a prognostic marker in patients with recurrent and/or metastatic (R/M) HNSCC treated with standard chemotherapy.MethodsThis retrospective, multicenter, noninterventional study assessed PD-L1 expression on archival R/M HNSCC tissue samples using the VENTANA PD-L1 (SP263) Assay. PD-L1 high was defined as PD-L1 staining of ≥ 25% TC, with exploratory scoring at TC ≥ 10% and TC ≥ 50%. The primary objective of this study was to estimate the prognostic value of PD-L1 status in terms of overall survival (OS) in patients with R/M HNSCC.Results412 patients (median age, 62.0 years; 79.9% male; 88.2% Caucasian) were included from 19 sites in seven countries. 132 patients (32.0%) had TC ≥ 25% PD-L1 expression; 199 patients (48.3%) and 85 patients (20.6%) had TC ≥ 10% and ≥ 50%, respectively. OS did not differ significantly across PD-L1 expression (at TC ≥ 25% cutoff median OS: 8.2 months vs TC < 25%, 10.1 months, P = 0.55) or the ≥ 10% and ≥ 50% cutoffs (at TC ≥ 10%, median OS: 9.6 months vs TC < 10%, 9.4 months, P = 0.32, and at TC ≥ 50%, median OS 7.9 vs TC < 50%, 10.0 months, P = 0.39, respectively).ConclusionsPD-L1 expression, assessed using the VENTANA PD-L1 (SP263) Assay, was not prognostic of OS in patients with R/M HNSCC treated with standard of care chemotherapies.Trial registration ClinicalTrials.gov, NCT02543476. Registered September 4, 2015.

1054P - Prognostic and clinicopathological significance of PD-L1 in patients with cervical cancer: A meta-analysis

BackgroundProgrammed cell death ligand 1 (PD-L1) expression has been shown to associate with poor prognosis in a variety of solid tumors. However, the prognostic value of PD-L1 expression in cervical cancer is still controversial. Therefore, we performed a meta-analysis to investigate the prognostic and clinicopathological impact of PD-L1 in cervical cancer. MethodsA comprehensive literature search was performed in the PubMed, EMBASE, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang databases. The correlation between PD-L1 expression and overall survival (OS), progression-free survival (PFS), and clinicopathological features was analyzed by hazard ratios (HR), odds ratios (OR) and corresponding 95% confidence intervals (CI). ResultsSeven studies with 783 patients were included in this meta-analysis. The combined HR and 95%CI of OS was 2.52 (1.09-5.83), p=0.031. The pooled results for PFS were HR=2.07, 95%CI=0.52-8.23, p=0.302. The results of subgroup analysis showed that PD-L1 was a significant prognostic factor of poor OS in Asian patients (HR=4.77, 95%CI=3.02-7.54, p<0.001) and of poor PFS in Asian patients (HR=4.78, 95%CI=1.77-12.91, p=0.002). However, the pooled results suggested that PD-L1 was not significantly correlated with lymph node metastasis, tumour size, FIGO stage, depth of invasion, lymph-vascular invasion, or age. ConclusionsThe results of this meta-analysis suggest that PD-L1 overexpression is related to poor OS in patients with cervical cancer and poor PFS in Asian patients with cervical cancer. This study also suggests that PD-L1 is a promising prognostic indicator for cervical cancer. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Elevated PD-L1 expression predicts poor survival outcomes in patients with cervical cancer

BackgroundProgrammed cell death ligand 1 (PD-L1) expression has been shown to associate with poor prognosis in a variety of solid tumors. However, the prognostic value of PD-L1 expression in cervical cancer is still controversial. Therefore, we carried a meta-analysis to investigate the prognostic and clinicopathological impact of PD-L1 in cervical cancer.MethodsA comprehensive literature search in was performed in PubMed, Embase, Web of Science, and Cochrane Library. The correlation between PD-L1 expression and overall survival (OS), progression-free survival (PFS), and clinicopathological features was analyzed by hazard ratios (HR), odds ratios (OR) and corresponding 95% confidence intervals (CI).ResultsSeven studies with 783 patients were included in this meta-analysis. The combined HR and 95% CI of OS was 2.52 (1.09–5.83), p = 0.031. The pooled results for PFS were HR = 2.07, 95% CI = 0.52–8.23, p = 0.302. The results of subgroup analysis showed that PD-L1 was a significant prognostic factor of poor OS in Asian patients (HR = 4.77, 95% CI = 3.02–7.54, p < 0.001) and of poor PFS in Asian patients (HR = 4.78, 95% CI = 1.77–12.91, p = 0.002). However, the pooled results suggested that PD-L1 was not significantly correlated with lymph node metastasis, tumor size, FIGO stage, depth of invasion, lymph-vascular invasion, or age.ConclusionsThe results of this meta-analysis suggest that PD-L1 overexpression is related to poor OS in patients with cervical cancer and poor PFS in Asian patients with cervical cancer. This study also suggests that PD-L1 is a promising prognostic indicator for cervical cancer.

PO-0780 Prognostic value of PD-L1 expression in locally advanced NSCLC treated with chemoradiotherapy

PO-0780 Prognostic value of PD-L1 expression in locally advanced NSCLC treated with chemoradiotherapy

Prevalence and prognostic value of PD-L1 expression in molecular subtypes of metastatic large cell neuroendocrine carcinoma (LCNEC)

BackgroundPulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare tumor with high mutational burden. Two subtypes of LCNEC are recognized, the co-mutated TP53 and RB1 group and the TP53 and STK11/KEAP1 group. We investigated PD-L1 and CD8 expression in a well characterized stage IV LCNEC cohort and compared expression in the two subtypes. MethodsImmunohistochemical (IHC) analysis for PD-L1 and CD8 was performed on pathological reviewed pretreatment tumor samples for 148 stage IV LCNEC. Data about targeted next generation sequencing (TNGS) (TP53, RB1, STK11, KEAP1) and IHC for RB1 were available for most tumors. IHC staining for PD-L1 (DAKO 28-8) was performed and scored positive if tumors showed ≥1% membranous staining. CD8 was scored for intra-tumor T-cells and stromal cells. ResultsPD-L1 IHC expression data could be generated in 98/148 confirmed LCNEC samples along with RB1 IHC (n = 97) of which 77 passed quality control for TNGS. PD-L1 expression was positive in 16/98 cases (16%); 5 (5%) with ≥50%. PD-L1 expression was equal in RB1 mutated and RB1 wildtype tumors. None of STK11 mutated tumors (n = 7) expressed PD-L1. PD-L1 expression was correlated with superior overall survival (OS), hazard ratio 0.55 ((95% Confidence Interval 0.31-0.96), p = 0.038). Intra-tumor CD8 was associated with PD-L1 expression (p = 0.021) and stromal and intra-tumor CD8 were correlated with improved OS (p = 0.037 and p = 0.026 respectively). ConclusionsPD-L1 expression was positive in 16% of stage IV LCNEC tumors. This was independent of molecular subtype but associated with CD8 expression. In LCNEC patients with PD-L1 and/or CD8 expression superior OS was observed.

Programmed death ligand 1 expression in early stage, resectable non-small cell lung cancer.

IntroductionFor several years non-small cell lung cancer (NSCLC) has been considered non-immunogenic. Recent advances in antitumor immunity brought to the discovery of checkpoints that modulate immune response against cancer. One of them is programmed death receptor 1 (PD-1) and its ligand (PD-L1). Although PD-L1 expression seems predictive of response to anti-PD-1/PD-L1 agents, its prognostic value is unclear. In this study we investigated the prognostic value of PD-L1 expression and its correlation with clinical-pathological characteristics in a cohort of surgically resected NSCLC.Material and methodsPD-L1 expression was evaluated in 289 surgically resected NSCLC samples by immunohistochemistry. Our cohort included patients not exposed to adjuvant chemotherapy. PD-L1 status was defined as: 1) PD-L1 high (tumor proportion score, TPS≥50%), PD-L1 low (TPS 1-49%), PD-L1 negative (TPS<1%); 2) PD-L1 positive (TPS≥50%) and negative (TPS<50%); 3) as a continuous variable.ResultsPatients were mostly males (79%), former or current smokers (81%), with a median age of 67 years, non-squamous histology (67.5%) and high-grade tumors (55%). PD-L1 tumors were 18.7%. There was no significant association with sex, age, smoking status and histology. A strong correlation between high PD-L1 expression and tumor grade was detected. The difference in median OS in the different groups of patients was not statistically significant.ConclusionPD-L1 is not prognostic in surgically resected NSCLC. The association with tumor differentiation suggests that grading could represent an easy-to-assess tool for selecting subjects potentially sensitive to immunotherapy warranting further investigations.