Comparison of the profiles of first-line PD-1/PD-L1 inhibitors for advanced NSCLC lacking driver gene mutations: a systematic review and Bayesian network meta-analysis
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PROVIDER: S-EPMC10568994 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
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Project description:We aimed to evaluate whether different driver mutations have varying impacts on the programmed cell death-ligand 1 (PD-L1) expression of non-small cell lung cancer (NSCLC), and whether the prognostic roles of PD-L1 amongst our patients were divergent. This was a single-institute study that included patients with NSCLC. Six driver mutations, PD-L1 status, and the outcomes of treatment were assessed. A total of 1,001 NSCLC patients were included for analysis. Overall, the PD-L1 positive (TPS ≥ 1%) and strong positive (TPS ≥ 50%) rates were 52.2% and 17.3%, respectively. As compared with wild type lung adenocarcinoma, EGFR-mutant and HER2-mutant patients had similarly low PD-L1 and strong PD-L1 positive rates. BRAF-mutant patients had numerically higher PD-L1 and strong PD-L1 positive rates. Patients with fusion mutation (ALK and ROS1) (aOR 2.32 [95% CI 1.10-4.88], P = 0.027 and 2.33 [95% CI 1.11-4.89], P = 0.026), KRAS mutation (aOR 2.58 [95% CI 1.16-5.75], P = 0.020 and 2.44 [95% CI 1.11-5.35], P = 0.026), and non-adenocarcinoma histology (aOR 2.73 [95% CI 1.72-4.34], P < 0.001 and 1.93 [95% CI 1.13-3.30], P = 0.016) all had significantly higher PD-L1 and strong PD-L1 positive rates. A trend towards longer survival was noted in ROS-1 rearranged and KRAS-mutant patients with strong PD-L1 expression who had received crizotinib and chemotherapy, respectively. In conclusion, individual driver mutations had various impacts on the PD-L1 expression of NSCLC patients. The prognostic role of PD-L1 may also be divergent amongst patients harboring different driver mutations.
| S-EPMC9387808 | biostudies-literature
Project description:ObjectivesThis study aims to explore how pre-existing conditions such as blood types, family history of cancer and comorbid diseases correlate with the genetic and programmed death-ligand 1 (PD-L1) expression that contributes to the heterogeneous biological behaviours of non-small cell lung cancer (NSCLC).Materials and methodsA cohort of 5507 NSCLC patients who underwent surgical resection between January 2014 and July 2018 was studied. Targeted next-generation sequencing was used to detect mutations in nine pivotal cancer-related genes, and immunohistochemical staining was applied to assess PD-L1 expression. Logistic regression analysis was employed to identify significant correlations.ResultsAll patients underwent NGS, with 1839 were also evaluated for PD-L1 expression. Several significant findings were found: ROS1 mutations were closely associated with a family history of lung cancer (OR 7.499, 95% CI 1.094 to 30.940, p=0.013). Epidermal growth factor receptor (EGFR) L858R mutations were common among patients with a family history of non-lung cancers and those with hypertension (OR 2.089, 95% CI 1.029 to 4.135, p=0.037 and OR 1.252, 95% CI 1.001 to 1.562, p=0.048, respectively). Pre-existing conditions such as diabetes and hepatitis B surface antigen positivity (OR 1.468, 95% CI 1.042 to 2.047, p=0.026 and OR 1.373, 95% CI 1.012 to 1.847, p=0.038, respectively) were correlated with EGFR exon 19 deletions. RhD negativity showed potential ties to BRAF mutations (OR 0.010, 95% CI 0.001 to 0.252, p=0.001). A history of tuberculosis linked to increased PD-L1 expression in immune cells (OR 3.597, 95% CI 1.295 to 14.957, p=0.034).ConclusionThis large-scale, cross-sectional study reveals a complex interplay between genetic mutations, immunological features and pre-existing conditions in NSCLC patients, offering insights that could inform personalised treatment strategies.
| S-EPMC11624786 | biostudies-literature
Project description:Despite the efficacy of a number of first-line treatments, most patients with advanced-stage non-small cell lung cancer (NSCLC) experience disease progression that warrants further treatment. In this review, we examine the role of novel active agents for patients who progress after first-line therapy and who are not candidates for targeted therapies. More therapeutic options are needed for the management of patients with NSCLC after failure of first-line chemotherapy. A PubMed search was performed for articles from January 2012 to May 2015 using the keywords NSCLC, antiangiogenic, immunotherapy, second-line, novel therapies and English language articles only. Relevant papers were reviewed; papers outside that period were considered on a case-by-case basis. A search of oncology congresses was performed to identify relevant abstracts over this period. In recent years, antiangiogenic agents and immune checkpoint inhibitors have been added to our armamentarium to treat patients with advanced NSCLC who have progressed on first-line chemotherapy. These include nintedanib, a triple angiokinase inhibitor; ramucirumab, a vascular endothelial growth factor receptor-2 antibody; and nivolumab, pembrolizumab and atezolizumab, just three of a growing list of antibodies targeting the programmed death receptor-1 (PD-1)/PD ligand-1 pathway. Predictive and prognostic factors in NSCLC treatment will help to optimise treatment with these novel agents. The approval of new treatments for patients with NSCLC after the failure of first-line chemotherapy has increased options after a decade of few advances, and holds promise for future evolution of the management of NSCLC.
| S-EPMC5729303 | biostudies-literature
Project description:ObjectiveOur previous economic assessment found that nivolumab was not cost-effective for Chinese patients with advanced non-small cell lung cancer (NSCLC) and without EGFR mutations or ALK translocations, when compared with the standard second-line drug docetaxel. However, a greater survival benefit with nivolumab was observed for patients with 1% or greater tumor programmed death ligand 1 (PD-L1) expression. In view of this, we designed the present analysis to explore whether it is cost-effective to use the PD-L1 test to guide second-line nivolumab treatment in China.Material and methodsA Markov model was established to project the lifetime costs and quality-adjusted life-years (QALYs) of three second-line treatment strategies: nivolumab and docetaxel (strategies without a PD-L1 test) and PD-L1 test-based strategy. Deterministic and probabilistic sensitivity analyses were performed to examine the robustness of our results. Additional price reduction and willingness-to-pay (WTP) threshold scenario analyses were performed to explore the impact of economic and health policies with Chinese characteristics on our results.ResultsThe PD-L1 test-based strategy costs approximately CNY 194,607 (USD 28,210) or more and yielded an additional 0.27 QALYs compared to the docetaxel strategy without a PD-L1 test, equating an incremental cost-effectiveness ratio (ICER) of CNY 731,089 (USD 105,978)/QALY. Deterministic sensitivity analyses showed that the price of nivolumab was the strongest source of variation in the ICERs. Probability sensitivity analysis showed that the probability for the PD-L1 test-based strategy being cost-effective increases with the increase of WTP thresholds.ConclusionFrom the perspective of the Chinese healthcare system, using a PD-L1 test to guide second-line nivolumab treatment was not cost-effective. The National Healthcare Security Administration negotiation on the price reduction of nivolumab was found to be the most effective action to improve its cost-effectiveness in China.
| S-EPMC8710478 | biostudies-literature
Project description:Background: Adenosquamous carcinoma of the lung (ASC) is a rare non-small-cell lung cancer (NSCLC) subtype combining components of squamous cell carcinoma (SCC) and adenocarcinoma (AC). Data on ASC, particularly in Caucasian populations, are limited. Methods: We reviewed clinicopathological and radiological characteristics of ASC patients diagnosed between 1996 and 2023. Patients were classified into AC-predominant ASC (AC-ASC) and SCC-predominant ASC (SCC-ASC) groups for analysis. Results: Among the 66 patients included, the median overall survival was 41.7 (95% CI, 25.0-54.4), while it was 48.1 (95% CI, 27.3-88.0) in patients treated with curative surgery (n = 44) and 15.3 (95% CI, 6.5-42.6) months for palliative patients (n = 22). The five-year survival rates were 39% and 26%, respectively. Recurrence occurred in 43% of stage I patients and was associated with worse survival (HR 3.303 (95% CI, 1.10-9.89) p = 0.033). AC-ASCs (n = 17) more frequently showed air-bronchogram (p = 0.002) and pleural effusions (p = 0.054) compared to SCC-ASCs (n = 26). SCC-ASCs exhibited more vascular invasion (p = 0.006) and PD-L1 values between 1 and 49% (TPS) (p = 0.032). The subtype did not influence survival. EGFR and ALK alterations were found in 17% and 2% of patients, respectively. Conclusions: Despite early-stage disease, ASC patients had a high recurrence rate, associated with worse survival. Clinicopathologic differences between AC-ASCs and SCC-ASCs did not influence survival.
| S-EPMC11476650 | biostudies-literature
Project description:Exosomal miRNAs involved in response to anti-PD-1/PD-L1 monotherapy in advanced NSCLC patients were successfully identified through the microoarray analysis.
2023-01-12 | GSE189045 | GEO
Project description:Background and aimThe objective of this retrospective, observational, noninterventional cohort study was to investigate prognostic factors of overall survival (OS) in patients with advanced non-small cell lung cancer (aNSCLC) and to develop a novel prognostic model.MethodsA total of 4049 patients with aNSCLC diagnosed between January 2011 and February 2020 who received atezolizumab, nivolumab, or pembrolizumab as second-line monotherapy were selected from a real-world deidentified database to build the cohort. Patients could not have received first-line treatment with clinical study drug(s) nor immune checkpoint inhibitors including anti-programmed cell death 1 (PD-1)/programmed death-ligand 1 (PD-L1), and anti-cytotoxic T-lymphocyte-associated protein 4 therapies.ResultsPatients had a median age of 69 years; 45% were female, 75% White, 70% had stage IV at initial diagnosis, and 70% had nonsquamous histology. A Cox proportional hazards model with lasso regularization was used to build a prognostic model for OS using 18 baseline demographic and clinical factors based on the real-world data cohort. The risk-increasing prognostic factors were abnormally low albumin and chloride levels, Eastern Cooperative Oncology Group performance status score ≥ 2, and abnormally high levels of alkaline phosphatase and white blood cells. The risk-decreasing prognostic factors were PD-L1 positivity, longer time from advanced diagnosis to start of first-line therapy, and higher systolic blood pressure. The performance of the model was validated using data from the OAK trial, and the c-index for the OAK trial validation cohort was 0.65 and 0.67 for the real-world data cohort.ConclusionsBased on baseline demographic and clinical factors from a real-world setting, this prognostic model was developed to discriminate the risk of death in patients with aNSCLC treated with checkpoint inhibitors as second-line monotherapy, and it performed well in the real-world data and clinical trial cohorts.
| S-EPMC9575492 | biostudies-literature
Project description:Although information on the PD-L1 expression and EGFR mutations in non-small cell lung cancer (NSCLC) is important for therapeutic strategies, the effect of these factors on postoperative recurrence and the association between each factor have remained unclear. We retrospectively assessed the PD-L1 expression and EGFR mutations in 280 NSCLC patients, and analyzed the associations by multivariate analyses. The hazard ratio (HR) of postoperative recurrence in cases with high (≥ 50%) PD-L1 expression regarding negative expression was 4.83 (95% confidence interval [CI] 1.51-15.5). The HR for the PD-L1 expression, considered a continuous variable, was 1.016 (95% CI 1.01-1.03). The HRs in cases with EGFR major and minor mutations were 0.42 (95% CI 0.14-1.25) and 0.63 (95% CI 0.18-2.15), respectively. The high PD-L1 (≥ 50%) expression was significantly associated with exon 21 L858R mutation (Ex21) of EGFR (odds ratio, 0.10; 95% CI 0.01-0.87). The risk of postoperative recurrence increased 1.016-fold for every 1% increase in the PD-L1 expression, and a marked increase in risk was observed for expression levels of ≥ 50%. Whereas EGFR mutations were not an independent risk factor. The high PD-L1 (≥ 50%) expression was negatively associated with Ex21. These findings may help identify NSCLC patients with an increased risk of postoperative recurrence.
| S-EPMC8410871 | biostudies-literature
Project description:Our aim was to evaluate real-world time on treatment (rwToT), overall and by KRAS mutation status, with first-line pembrolizumab monotherapy for advanced non-small cell lung cancer (NSCLC) in real-world oncology practice in the US. rwToT is a readily available, intermediate-range endpoint that is moderately to highly correlated with overall survival in clinical trials and real-world data. Using deidentified electronic medical record data, we studied patients with ECOG performance status (PS) of 0-2 who initiated pembrolizumab (1 November 2016 to 31 March 2020) for advanced NSCLC with programmed death-ligand 1 (PD-L1) expression ≥ 50% and without EGFR/ALK/ROS1 genomic alterations. The data cutoff was 31 March 2021, and the median study follow-up was 34 months. The Kaplan-Meier median rwToT with first-line pembrolizumab monotherapy was 7.4 months (95% CI, 6.3-8.1) for 807 patients with PS 0-1, which was consistent with the median treatment duration in the KEYNOTE-024 trial (7.9 months). The median rwToT for 237 patients with PS 2 was 2.1 months (95% CI, 1.4-2.8). For those with KRAS-mutated and KRAS wild-type nonsquamous NSCLC and PS 0-1, the median rwToT was 7.6 months and 7.0 months, respectively. Our findings suggest long-term benefit of first-line pembrolizumab monotherapy for advanced NSCLC with PD-L1 expression ≥ 50% in real-world settings in the US, particularly for patients with good performance status at the start of therapy, irrespective of KRAS status.
| S-EPMC8870405 | biostudies-literature
Project description:Although many studies have addressed the prognostic value of programmed cell death-ligand 1 (PD-L1) expression in lung cancer, the results remain controversial. A systematic search of the PubMed, EMBASE, and Cochrane Library databases was performed to identify the correlation between PD-L1 expression and driver mutations and overall survival (OS). This meta-analysis enrolled a total of 11,444 patients for 47 studies, and the pooled results showed that increased PD-L1 expression was associated with poor prognosis (HR = 1.40, 95% CI: 1.19-1.65, P < 0.001). In subgroup analysis stratified according to histology types, the pooled results demonstrated that increased PD-L1 expression was an unfavorable prognostic factor for non-small cell lung cancer (NSCLC) (HR = 1.26, 95% CI: 1.05-1.52, P = 0.01) and pulmonary lymphoepithelioma-like carcinoma (LELC) (HR = 3.04, 95% CI: 1.19-7.77, P = 0.02), rather than small cell lung cancer (SCLC) (HR = 0.62, 95% CI: 0.27-1.39, P = 0.24). The pooled ORs indicated that PD-L1 expression was associated with gender, smoking status, histology, differentiation, tumour size, lymph nodal metastasis, TNM stage and EGFR mutation. However, PD-L1 expression was not correlated with ALK rearrangement and KRAS mutations.
| S-EPMC5578960 | biostudies-literature