Dataset Information

The efficacy of anti-PD-1/PD-L1 therapy and its comparison with EGFR-TKIs for advanced non-small-cell lung cancer.

ABSTRACT: To better understand the efficacy and safety of anti-PD-1/PD-L1 therapy (atezolizumab, pembrolizumab, nivolumab) in patients with previously treated advanced non-small-cell lung cancer (NSCLC).The Cochrane Controlled Trial Register, Embase, Medline, and the Science Citation Index were searched for prospective published reports of atezolizumab, pembrolizumab, nivolumab in previously treated patients with advanced NSCLC.Finally, we identified 14 prospective published reports including four trials of atezolizumab covering 542 subjects, three trials of pembrolizumab covering 1566 subjects, seven trials of nivolumab covering 1678 subjects. When compared to docetaxel, anti-PD-1/PD-L1 therapy could significantly improve overall survival (hazard ratio [HR] 0.67, P<0.001) and progression-free survival (HR 0.83, P=0.002) for previously treated patients with advanced NSCLC. Anti-PD-1/PD-L1 therapy produced an overall response rate of 19% in the 2374 evaluable patients. When using docetaxel as the common comparator, indirect comparison of anti-PD-1/PD-L1 therapy versus EGFR-TKIs showed progression-free survival benefit (HR 0.62, P<0.001) and overall survival benefit (HR 0.60, P<0.001) for those patients with EGFR wild-type. Meanwhile, for those EGFR mutant patients, indirect comparison indicated that anti-PD-1/PD-L1 therapy was inferior to EGFR-TKIs therapy in terms of progression-free survival (HR 3.20, P<0.001), but no survival difference (HR 1.30, P=0.18).Anti-PD-1/PD-L1 therapy could produce progression-free survival and overall survival improvement over docetaxel for patients with previously treated NSCLC. For EGFR wild-type patients, anti-PD-1/PD-L1 therapy seemed to prolong progression-free survival and overall survival when compared to EGFR-TKIs. Meanwhile, for these EGFR mutant patients, anti-PD-1/PD-L1 therapy was inferior to EGFR-TKIs therapy in terms of progression-free survival.

SUBMITTER: Sheng Z

PROVIDER: S-EPMC5593686 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The efficacy of anti-PD-1/PD-L1 therapy and its comparison with EGFR-TKIs for advanced non-small-cell lung cancer.

Sheng Zhixin Z Zhu Xu X Sun Yanhua Y Zhang Yanxia Y

Oncotarget 20170608 34

<h4>Purpose</h4>To better understand the efficacy and safety of anti-PD-1/PD-L1 therapy (atezolizumab, pembrolizumab, nivolumab) in patients with previously treated advanced non-small-cell lung cancer (NSCLC).<h4>Methods</h4>The Cochrane Controlled Trial Register, Embase, Medline, and the Science Citation Index were searched for prospective published reports of atezolizumab, pembrolizumab, nivolumab in previously treated patients with advanced NSCLC.<h4>Results</h4>Finally, we identified 14 pros ...[more]

PMID: 28915714

Similar Datasets

Project description:IntroductionThe epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in combination with anti-vascular endothelial growth factor receptor (VEGFR) agents have shown improved survival outcomes in recent studies. However, its efficacy related to survival outcomes as a first- or second-line agent and based on generations remains to be explored. This study estimated the survival outcomes of EGFR-TKIs plus anti-VEGFR in combination in defined populations of advanced non-small cell lung cancer (NSCLC) patients overall, as a first- or second line of treatment, with different generations of EGFR-TKIs and EGFR-TKIs plus bevacizumab combination as a subgroup.MethodsA literature search was conducted using PubMed, SCOPUS, Cochrane Library, and ClinicalTrials.gov databases through June 2023 to identify primary research reporting the survival outcomes of EGFR-TKIs in combination with anti-VEGFR agents in patients with advanced NSCLC. Studies that were single-arm, published in non-English languages, and had missing data on survival outcomes were excluded. A meta-analysis was conducted to generate pooled hazard ratios (HRs) with 95% confidence intervals (CI) for overall survival (OS) and progression-free survival (PFS). Methodological quality and risk of bias in studies were assessed using the Cochrane Handbook for Systematic Reviews of Interventions risk of bias tool.ResultsA total of 20 randomized controlled trials were included in the qualitative synthesis, and 11 (2182 participants) were included in the meta-analysis. Patients' median age ranged from 58 to 68 years; 36% to 70% of patients were female; most of them had IIIa/b to IV stage cancer. In meta-analyses, the EGFR-TKIs plus anti-VEGFR combination resulted in improved PFS (HR, 0.73; 95% CI: 0.61, 0.86; p < 0.00001) in patients with advanced NSCLC but had no impact on OS (HR, 0.93; 95% CI: 0.79, 1.10; p = 0.41). The first line of treatment and first-generation EGFR-TKIs with the combination also improved the PFS (HR, 0.64; 95% CI: 0.57, 0.71; p < 0.00001; HR, 0.63; 95% CI: 0.56, 0.71; p < 0.00001) respectively, however, had no impact on OS.ConclusionsOur meta-analysis indicated EGFR-TKIs with anti-VEGFR in combination not only improved overall PFS but also showed similar results to a first line and first-generation agent compared to EGFR-TKI alone.

Project description:BackgroundDespite disappointing outcomes from immuno-monotherapy, studies reported that NSCLC patients with EGFR mutation may possibly benefit from combined immunotherapy. Whether the response to prior EGFR-TKI has association with the outcomes of subsequent immunotherapy remains unclear.Patients and methodsAdvanced NSCLC patients with resistance to EGFR-TKIs and received ICI treatment from January 2016 to June 2019 were retrospectively analyzed. Single cell sequencing and flow cytometry were conducted to explore the difference of cell components in tumor microenvironments (TME). A 1:3 matched case-control study was conducted to compare the clinical effects of combined immunotherapy with standard chemotherapy as second-line treatment.ResultsFifty-eight patients treated with anti-PD-1/PD-L1 based immunotherapy behind EGFR-TKI treatment were enrolled. Correlation analysis showed TKI-PFS had a significantly negative association with corresponding IO-PFS (r = -0.35, p = 0.006). TKI-PFS cutoff 10 months had the most significant predictive function for posterior immunotherapy and was validated to be an independent predictor by uni- and multivariate analyses. Kaplan-Meier analysis showed that patients with TKI-PFS less than 10 months had significantly prolonged IO-PFS and higher ORR than those with long (median PFS, 15.1 vs 3.8 months; HR, 0.26, p = 0.0002; ORR, 31.8 versus 10%, p = 0.04). Single cell RNA-seq revealed that the cell components were varied among patients after treatment with EGFR-TKI. Patients with short TKI-PFS demonstrated a relatively higher proportion of CD8 effector cells and lower ratio of M2 like macrophage to M1 like macrophages, which was validated by flow cytometry. Case-control study demonstrated that combined immunotherapy achieved significantly longer PFS (HR, 0.51, 95% CI: 0.31-0.85, p = 0.02), longer OS (HR, 0.48, 95% CI: 0.26-0.89, p = 0.05) and higher ORR (33.3 vs 10.0%, p = 0.02) than traditional chemotherapy for patients with short TKI-PFS.ConclusionPatients with short TKI-PFS conferred better response to immunotherapy than those with long. The status of TME were different among those two populations. Combined ICI treatment could promisingly be a better choice than classical chemotherapy in second-line setting for patients with short TKI-PFS and no T790M mutation. Underlying mechanisms need to be further explored.

Project description:BackgroundThe present study aimed to investigate the determinant factors of survival in patients with pretreated advanced stage non-small cell lung cancer (NSCLC) who received anti-PD-1/PD-L1 therapy.MethodsIn this observational retrospective study, the clinical profiles and laboratory parameters of patients with NSCLC treated with anti-PD-1/PD-L1 therapy were consecutively collected. Lung Immune Prognostic Index (LIPI) was calculated based on the derived neutrophil-to-lymphocyte ratio (dNLR) and lactate dehydrogenase level (LDH). Modified Glasgow Prognostic Score (mGPS) was calculated based on serum C reactive protein and albumin, and tumor mutation burden (TMB) was calculated using a targeted next-generation sequencing panel based on 422 cancer-relevant genes. The primary and secondary end points were overall survival (OS) and progression-free survival (PFS), respectively. The Cox regression model was used to identify the potential determinant factors of survival benefit. Trained oncologists at Sun Yat-sen University Cancer Center followed all of the participants through visits to doctors' offices or via telephone calls to determine their clinical status.ResultsSeventy-three patients were included in our study. With a median follow up time of 637 days, there was a significant difference in PFS between patients with high TMB compared to those with low TMB (3.7 vs. 2.1 months; P=0.004), while no significant difference was found in OS (14.0 vs. 16.4 months; P=0.972). Patients with a good LIPI score had a significantly longer OS compared to patients with a poor LIPI score (19.2 vs. 12.6 months; P=0.010). The median OS in patients with a good and a poor mGPS was 16.8 and 4.3 months, respectively (P=0.029). In multivariate analysis, TMB was found to be significantly associated with PFS (HR, 0.38; 95% CI: 0.21-0.69; P=0.002), while LIPI score was found to be significantly associated with OS (HR, 0.50; 95% CI: 0.28-0.89; P=0.012).ConclusionsIn the present study, LIPI score was a significant determinant of OS in patients with advanced NSCLC who received ICIs; however, TMB was only associated with PFS and not associated with OS.

Dataset Information

The efficacy of anti-PD-1/PD-L1 therapy and its comparison with EGFR-TKIs for advanced non-small-cell lung cancer.

Publications

The efficacy of anti-PD-1/PD-L1 therapy and its comparison with EGFR-TKIs for advanced non-small-cell lung cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets