scholarly journals P1.04-71 Tumor Burden Is Not Associated with Efficacy of Immune Checkpoint Inhibitors in Advanced Lung Cancer

2019 ◽  
Vol 14 (10) ◽  
pp. S469
Author(s):  
D. Gerber ◽  
V. Popat ◽  
R. Lu ◽  
J. Saltarski ◽  
Y. Gloria-Mccutchen ◽  
...  
2020 ◽  
Vol 25 (6) ◽  
pp. 515-522 ◽  
Author(s):  
Vinita Popat ◽  
Rong Lu ◽  
Murtaza Ahmed ◽  
Jason Y. Park ◽  
Yang Xie ◽  
...  

2020 ◽  
Author(s):  
Xiaorong Zhou ◽  
Chenchen Li ◽  
Zhao Zhang ◽  
Daniel Y. Li ◽  
Jinwei Du ◽  
...  

AbstractBackgroundTyrosine Kinases Inhibitors (TKIs), VEGF/VEGF receptor inhibitors (VEGFIs, bevacizumab) and immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced cancer including non-small-cell lung cancer (NSCLC). Cell-free DNA (cfDNA) has been adapted as a convenient liquid biopsy that reflects characteristics of the status of both the primary and metastatic tumors, assisting in personalized medicine. This study aims to evaluate the utility of cfDNA as a prognostic biomarker and efficacy predictor of chemotherapy with or without these precision therapies in NSCLC patients.MethodsPeripheral cfDNA levels were quantified in 154 patients with NSCLC before (baseline) and after (post-chemotherapy) the first target cycle of chemotherapy. These patients were divided into four subgroups receiving chemotherapy only, chemotherapy plus TKIs, chemotherapy plus VEGFIs, and chemotherapy plus immune checkpoint inhibitors (ICIs), respectively. The correlations of cfDNA with tumor burden, clinical characteristics, progression-free survival (PFS), objective response ratio (ORR), and therapy regimens were analyzed.ResultsBaseline cfDNA, but not post-chemotherapy, positively correlates with tumor burden. cfDNA Ratio (post-chemotherapy/baseline) well distinguished responsive individuals (CR/PR) from non-responsive patients (PD/SD). Additionally, cfDNA Ratio was found to be negatively correlated with PFS in lung adenocarcinoma (LUAD), but not in lung squamous-cell carcinoma (LUSC). LUAD patients with low cfDNA Ratio benefit significantly including prolonged PFS and improved ORR, compared with those with high cfDNA Ratio. When stratified by therapy regimen, the predictive value of cfDNA Ratio is significant in patients with chemotherapy plus VEGFIs.ConclusionThe kinetics of plasma cfDNA during the chemotherapy may function as a prognostic biomarker and efficacy predictor for NSCLC patients.


2020 ◽  
Vol 40 (5) ◽  
Author(s):  
Jun Shao ◽  
Chengdi Wang ◽  
Pengwei Ren ◽  
Yuting Jiang ◽  
Panwen Tian ◽  
...  

Abstract Background: Immune checkpoint inhibitors (ICIs) emerged as the preferred therapy in advanced lung cancer, understanding the treatment- and immune-related adverse events of these drugs is of great significance for clinical practice. Materials and methods: PubMed, Embase, Cochrane library and major conference proceedings were systematically searched for all randomized controlled trials (RCTs) in lung cancer using PD-1/PD-L1/CTLA-4 inhibitors. The outcomes included treatment-related adverse events (TRAEs) and several organ specific immune-related adverse events (IRAEs). Results: 24 RCTs involving 14,256 patients were included. There was a significant difference for ICI therapy in the incidence of any grade of TRAEs (RR: 0.90; 95%CI: 0.84–0.95; P=0.001) and a lower frequency of grade 3-5 of TRAEs (RR: 0.65; 95%CI: 0.51–0.82; P<0.001). Patients treated with ICI therapy in non–small-cell lung cancer (NSCLC) were less reported TRAEs than in small cell lung cancer (SCLC). A lower risk of TRAEs was favored by anti-PD-1 inhibitors over anti-PD-L1 antibodies and anti-CTLA-4 drugs. The most common organ specific IRAE was hypothyroidism that occurred 8.7%. The incidence of pneumonitis and hepatitis reached 4.5% and 4.0% respectively. Compared with patients treated in control arms, those treated with ICI drugs were at higher risk for each organ specific adverse event including colitis, hepatitis, pneumonitis, hypothyroidism and hypophysitis. Conclusions: ICI therapy was safer than chemotherapy, especially ICI monotherapy such as anti-PD-1 antibodies in NSCLC. Compared with standard treatments, ICI drugs increased the risk of organ-specific IRAEs, although the overall incidence remained low.


2021 ◽  
Vol 12 ◽  
Author(s):  
Yi-Dan Yan ◽  
Jiu-Jie Cui ◽  
Jie Fu ◽  
Ying-Jie Su ◽  
Xiao-Yu Chen ◽  
...  

BackgroundImmune checkpoint inhibitors (ICIs) have become one of the standard treatment options for advanced lung cancer. However, adverse events (AEs), particularly immune–related AEs (irAEs), caused by these drugs have aroused public attention. The current network meta-analysis (NMA) aimed to compare the risk of AEs across different ICI–based regimens in patients with advanced lung cancer.MethodsWe systematically searched the PubMed, EMBASE, and Cochrane Library databases (from inception to 19 April 2021) for relevant randomized controlled trials (RCTs) that compared two or more treatments, with at least one ICI administered to patients with advanced lung cancer. The primary outcomes were treatment–related AEs and irAEs, including grade 1–5 and grade 3–5. The secondary outcomes were grade 1–5 and grade 3–5 irAEs in specific organs. Both pairwise and network meta-analyses were conducted for chemotherapy, ICI monotherapy, ICI monotherapy + chemotherapy, dual ICIs therapy, and dual ICIs + chemotherapy for all safety outcomes. Node–splitting analyses were performed to test inconsistencies in network. Sensitivity analyses were adopted by restricting phase III RCTs and studies that enrolled patients with non–small cell lung cancer.ResultsOverall, 38 RCTs involving 22,178 patients with advanced lung cancer were enrolled. Both pooled incidence and NMA indicated that treatments containing chemotherapy increased the risk of treatment–related AEs when compared with ICI-based regimens without chemotherapy. As for grade 1–5 irAEs, dual ICIs + chemotherapy was associated with the highest risk of irAEs (probability in ranking first: 50.5%), followed by dual-ICI therapy (probability in ranking second: 47.2%), ICI monotherapy (probability in ranking third: 80.0%), ICI monotherapy + chemotherapy (probability in ranking fourth: 98.0%), and finally chemotherapy (probability in ranking fifth: 100.0%). In grade 3–5 irAEs, subtle differences were observed; when ranked from least safe to safest, the trend was dual ICIs therapy (60.4%), dual ICIs + chemotherapy (42.5%), ICI monotherapy (76.3%), ICI monotherapy + chemotherapy (95.0%), and chemotherapy (100.0%). Furthermore, detailed comparisons between ICI–based options provided irAE profiles based on specific organ/system and severity.ConclusionsIn consideration of overall immune–related safety profiles, ICI monotherapy + chemotherapy might be a better choice among ICI–based treatments for advanced lung cancer. The safety profiles of ICI–based treatments are various by specific irAEs and their severity.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero, identifier CRD42021268650


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15058-e15058
Author(s):  
Nune Karapetyan ◽  
Davit Zohrabyan ◽  
Jemma Arakelyan ◽  
Lilit Harutyunyan ◽  
Samvel Bardakhchyan ◽  
...  

e15058 Background: Over the past few years PD-1/PD-L1 pathway blockade through immune checkpoint inhibitors appeared to be an effective treatment approach in advanced lung cancer. The current study aims to investigate the utilization of immunotherapy for lung cancer management purposes in Armenia. Methods: For this retrospective, hospital-based cohort study census sampling method was approached. Data was collected on all the patients who were diagnosed with stage III and IV lung cancer and passed treatment in the departments of Adult Solid Tumors in Hematology Center after prof. Yeolyan and Institute of Surgery after Mikaelyan from 01.05.2019 till 12.01.2020. The time period was selected based on the initiation of PD-L1 testing in Armenia. The prevalence of non-small cell (NSCLC) and small cell (SCLC) lung cancer was calculated. The patients’ PD-L1 testing performance, subsequent immunotherapy utilization, and developed adverse effects were evaluated. Results: According to the hospital-based data, during the mentioned time period 60 patients diagnosed with stage III and IV lung cancer received treatment in the two units. In the cohort, the patients’ median age was 65,5 years (range 46 – 88). The male-to-female ratio was 5.6. The prevalence of NSCLC and SCLC was 61.7% and 28.3% respectively. At the time of follow-up on 10.02.2020, 74.4% of NSCLC patients and 64.7% of SCLC patients were alive. Of the 43 NSCLC subjects, only 11 were checked for the PD-L1 status. Among them, 7 were determined to be PD-L1 positive and 5 of them received immunotherapy. For SCLC patients PD-L1 status wasn’t checked. Of 17 SCLC patients, only one has received immunotherapy. Overall only one case of immunotherapy related adverse effect was observed (severe rash and pruritus). At the time of follow-up, one of the six patients who underwent immunotherapy was dead. Conclusions: The presented data demonstrate a lack of PD-L1 test performance and underutilization of immunotherapy treatment. In the future, it is recommended to perform a nationwide study on the current topic to assess the immune checkpoint inhibitors impact on the survival rates of advanced lung cancer patients.


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