Predictors of Response, Progression Free Survival, and Overall Survival in Lung Cancer Patients Treated with Immune Checkpoint Inhibitors

2021 ◽  
Author(s):  
Regan M. Memmott ◽  
Adam R. Wolfe ◽  
David P. Carbone ◽  
Terence M. Williams
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Free Survival ◽  
Lung Cancer Patients ◽  
Predictors Of Response

scholarly journals The Effectiveness and Safety of Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer Patients With Stage III/IV: A Multicenter Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Jason C. Hsu ◽  
Phung-Anh Nguyen ◽  
Yen-Tzu Chen ◽  
Szu-Chun Yang ◽  
Chien-Chung Lin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Adverse Drug Events ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Small Cell Lung ◽  
Lung Cancer Patients

Immune checkpoint inhibitors (ICIs) have been approved to treat patients with various cancer types, including lung cancer, in many countries. This study aims to investigate the effectiveness and safety of ICIs under different treatment conditions of non-small cell lung cancer patients. A population-based retrospective cohort study was conducted using the electronic health records of three medical centers in Taiwan. From January 01, 2016, to November 30, 2018, a total of 91 ICIs and 300 traditional chemotherapy users who had undergone stage III and IV lung cancer treatment were included in the study. We performed the randomized matched pair design by selecting a Chemotherapy subject for each ICI patient in the sample population. All subjects were monitored from the date of taking ICIs or chemotherapy drugs until the event of death, loss to follow-up, or were occurred with any defined adverse events. Kaplan-Meier estimators and cox proportional hazard regression models were used to compute the overall survival, efficacy, and safety of the ICIs group. The median overall survival (OS) in the ICI and Chemo groups after matching was 11.2 months and 10.5 months, respectively. However, the results showed no significant OS differences between ICIs and chemo groups for both before and after matching (HR,1.30; 95%CI, 0.68-2.46; p=0.428 before matching and HR,0.96; 95CI%, 0.64-1.44; p=0.838 after matching). We observed that with the higher amount of PD-L1, the length of the patients’ overall survival was (positive vs. negative PD-L1, HR,0.21; 95%CI, 0.05-0.80; p=0.022). The incidences of serious adverse drug events above grade 3 in the ICIs and traditional chemo groups were 12.7% and 21.5%, respectively. We also found that the number of AEs was less in ICIs than in the Chemo group, and the AEs that occurred after treatments were observed earlier in the ICIs compared to the Chemo group. ICIs drugs were observed to be safer than traditional chemotherapy as they had a lower risk of serious adverse drug events. It is necessary to pay attention to immune-related side effects and provide appropriate treatment. Furthermore, the patient’s physical status and PD-L1 test can be used to evaluate the clinical effectiveness of ICIs.

Dynamic levels of extracellular vesicle PD-L1 and complementary radiomics for the prediction of the response to immune checkpoint inhibitors in lung cancer patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21144-e21144
Author(s):  
Christian Diego Rolfo ◽  
Diego de Miguel Perez ◽  
Alessandro Russo ◽  
Murat AK ◽  
Muthukumar Gunasekaran ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Immune Response ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Circulating Biomarkers ◽  
Current Standard ◽  
Lung Cancer Patients

e21144 Background: Immune-checkpoint inhibitors (ICIs) have revolutionized the therapeutic landscape of lung cancer patients. However, its low treatment efficacy is still an issue and the current standard of care tissue PD-L1 presents high variability. Liquid biopsy is a promising tool in the discovery of biomarkers in body fluids. In particular, extracellular vesicles (EVs) can present PD-L1 in their membranes, playing a role in the inhibition of the anti-tumor immune response. Likewise, TGF-β is crucial in the immune response found in the circulation and into EVs. On the other hand, radiomics analysis of conventional imaging provides information about tumor heterogeneity and immune response. Hence, we aimed to evaluate the predictive role of circulating biomarkers in lung cancer patients undergoing ICIs and the additional value of radiomics data. Methods: This is a retrospective analysis of 30 advanced/metastatic non-small lung cancer patients treated with ICIs. Plasma samples were collected at baseline and at 8 weeks during treatment, matching the first response evaluation. Patients with complete, partial response, or stable disease were classified as responders and those with progressive disease as non-responders following RECIST v1.1. EVs were isolated from plasma by ultracentrifugation and PD-L1 expression was revealed by immunoblot. Circulating and EV levels of TGF-β were analyzed by ELISA. Additionally, 400 radiomics features from target and non-target lesions were analyzed to evaluate response in 24 patients according to RECIST v1.1 and irRECIST. Robustness of predictive models was validated by ridge penalty and leave-one-out cross-validation. Results: The analysis of the dynamics of EV PD-L1 during treatment identified increased levels in non-responders in comparison to responders ( p= 0.012), while tissue PD-L1 levels were not associated to the response ( p= 0.585). The predictive model for EV PD-L1 reported a high accuracy with an area under the curve (AUC) = 77%, 91.7% sensitivity, and 61.1% specificity. The combination with radiomics, improved the accuracy and reported an AUC = 83%, 82% sensitivity, and 77% specificity. Additionally, the analysis of the association of the circulating biomarkers with the outcome revealed that increasing dynamics of EV PD-L1 and high baseline EV TGF-β were associated with shorter progression-free survival and overall survival, outperforming the circulating levels of TGF-β. Conclusions: This pilot study demonstrated that EV PD-L1 could serve as better predictive factor than tissue PD-L1 for the stratification of lung cancer patients undergoing ICIs and that it could be complemented with radiomics. Moreover, EV levels of PD-L1 and TGF-β have potential for the stratification and prognosis of patients treated with ICIs and their novel combinations with TGF-β blockade.

scholarly journals Immune-Related Adverse Events Predict the Efficacy of Immune Checkpoint Inhibitors in Lung Cancer Patients: A Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Donghui Wang ◽  
Cen Chen ◽  
Yanli Gu ◽  
Wanjun Lu ◽  
Ping Zhan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Lung Cancer Patients

BackgroundImmune-related adverse events (irAEs) have been reported to be associated with the efficacy of immunotherapy. Herein, we conducted a meta-analysis to demonstrate that irAEs could predict the efficacy of immune checkpoint inhibitors (ICIs) in lung cancer patients.MethodsLiterature on the correlation between irAEs and the efficacy of immunotherapy in lung cancer patients were searched to collect the data on objective response rate (ORR), overall survival (OS), or progression-free survival (PFS) of the patients. These data were incorporated into the meta-analysis.ResultsA total of 34 records encompassing 8,115 patients were examined in this study. The irAEs occurrence was significantly associated with higher ORR {risk ratio (RR): 2.43, 95% confidence interval (CI) [2.06–2.88], p < 0.00001} and improved OS {hazard ratio (HR): 0.51, 95% CI [0.43–0.61], p < 0.00001}, and PFS (HR: 0.50, 95% CI [0.44–0.57], p < 0.00001) in lung cancer patients undergoing ICIs. Subgroup analysis revealed that OS was significantly longer in patients who developed dermatological (OS: HR: 0.53, 95%CI [0.42–0.65], p < 0.00001), endocrine (OS: HR: 0.55, 95%CI [0.45–0.67], p < 0.00001), and gastrointestinal irAEs (OS: HR: 0.58, 95%CI [0.42–0.80], p = 0.0009) than in those who did not. However, hepatobiliary, pulmonary, and high-grade (≥3) irAEs were not correlated with increased OS and PFS.ConclusionThe occurrence of irAEs in lung cancer patients, particularly dermatological, endocrine, and gastrointestinal irAEs, is a predictor of enhanced ICIs efficacy.

scholarly journals Higher CD4/CD8 ratio of pleural effusion predicts better survival for lung cancer patients receiving immune checkpoint inhibitors

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Po-Hsin Lee ◽  
Tsung-Ying Yang ◽  
Kun-Chieh Chen ◽  
Yen-Hsiang Huang ◽  
Jeng-Sen Tseng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Pleural Effusion ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Lung Cancer Patients ◽  
Predicting Factor ◽  
Type 3

AbstractPleural effusion is a rare immune-related adverse event for lung cancer patients receiving immune checkpoint inhibitors (ICIs). We enrolled 281 lung cancer patients treated with ICIs and 17 were analyzed. We categorized the formation of pleural effusion into 3 patterns: type 1, rapid and massive; type 2, slow and indolent; and type 3, with disease progression. CD4/CD8 ratio of 1.93 was selected as the cutoff threshold to predict survival. Most patients of types 1 and 2 effusions possessed pleural effusion with CD4/CD8 ratios ≥ 1.93. The median OS time in type 1, 2, and 3 patients were not reached, 24.8, and 2.6 months, respectively. The median PFS time in type 1, 2, and 3 patients were 35.5, 30.2, and 1.4 months, respectively. The median OS for the group with pleural effusion CD4/CD8 ≥ 1.93 and < 1.93 were not reached and 2.6 months. The median PFS of those with pleural effusion CD4/CD8 ≥ 1.93 and < 1.93 were 18.4 and 1.2 months. In conclusion, patients with type 1 and 2 effusion patterns had better survival than those with type 3. Type 1 might be interpreted as pseudoprogression of malignant pleural effusion. CD4/CD8 ratio ≥ 1.93 in pleural effusion is a good predicting factor for PFS.

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