scholarly journals PCN56 - TREATMENT EFFECT MODIFICATION (EM) OF ANTICANCER THERAPIES IN FIRST-LINE ADVANCED NON-SMALL CELL LUNG CANCER (ANSCLC): A SYSTEMATIC ASSESSMENT OF TRIAL DATA

2018 ◽  
Vol 21 ◽  
pp. S23
Author(s):  
S. Wang ◽  
N. Varol ◽  
N. Waser ◽  
J.C. Thompson ◽  
J.R. Penrod ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Treatment Effect ◽  
Effect Modification ◽  
Small Cell ◽  
Trial Data ◽  
Small Cell Lung ◽  
First Line ◽  
Systematic Assessment

scholarly journals Consideration of Surrogate Endpoints for Overall Survival Associated With First-Line Immunotherapy in Extensive-Stage Small Cell Lung Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Shuang Zhang ◽  
Shuang Li ◽  
Yanan Cui ◽  
Peiyan Zhao ◽  
Xiaodan Sun ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Treatment Effect ◽  
Small Cell ◽  
Surrogate Endpoints ◽  
Small Cell Lung ◽  
First Line ◽  
Extensive Stage

BackgroundThe combination of immune checkpoint inhibitors (ICIs) and chemotherapy is known to improve overall survival (OS) in patients with extensive-stage small cell lung cancer (ES-SCLC). ICIs have different response patterns and survival kinetics characteristics from those of the traditional chemotherapy. In first-line treatment for ES-SCLC, there is an urgent need for surrogate endpoints for the early and accurate prediction of OS. This study aimed to assess progression-free survival (PFS), milestone OS rate, milestone restricted mean survival time (RMST), overall response rate (ORR), and disease control rate (DCR) as proposed surrogate endpoints for OS in ES-SCLC for first-line immunotherapy trials.MethodsBetween January 1, 2013, and December 2020, published articles on randomized clinical trials of ICIs plus chemotherapy in patients with ES-SCLC as first-line therapy were searched in PubMed. Abstracts from the ESMO, ASCO, and WCLC, reported from 2018 onwards, were also searched. A weighted regression analysis based on the weighted least squares method was performed on log-transformed estimates of treatment effect, and the determination coefficient (R2) was calculated to evaluate the association between treatment effect on the surrogate endpoint and OS.ResultsSeven trials, representing 3,009 patients, were included to make up a total of 16 analyzed arms. The ratio of the 12-month OS milestone rate (r = −0.790, P = 0.011, R2 = 0.717) and 12-month OS milestone RMST (r = 0.798, P = 0.010, R2 = 0.702) was strongly correlated with the hazard ratio (HR) for OS. The strongest association was observed between the ratio of the 24-month OS milestone RMST and the HR for OS (r = 0.922, P = 0.001, R2 = 0.825). No associations were observed between the HR for OS and PFS and the RR for ORR and DCR.ConclusionsThe results suggested a strong correlation among the ratio of OS milestone rates at 12 months, ratios of OS milestone RMSTs at 12 and 24 months, and HR for OS. The results indicate that OS milestone rates and OS milestone RMSTs could be considered surrogate endpoints of OS in future first-line immunotherapy trials for ES-SCLC.

scholarly journals Biomarkers and Gene Signatures to Predict Durable Response to Pembrolizumab in Non-Small Cell Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3828
Author(s):  
Anello Marcello Poma ◽  
Rossella Bruno ◽  
Iacopo Pietrini ◽  
Greta Alì ◽  
Giulia Pasquini ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Cell ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Durable Response ◽  
Nsclc Patients

Pembrolizumab has been approved as first-line treatment for advanced Non-small cell lung cancer (NSCLC) patients with tumors expressing PD-L1 and in the absence of other targetable alterations. However, not all patients that meet these criteria have a durable benefit. In this monocentric study, we aimed at refining the selection of patients based on the expression of immune genes. Forty-six consecutive advanced NSCLC patients treated with pembrolizumab in first-line setting were enrolled. The expression levels of 770 genes involved in the regulation of the immune system was analysed by the nanoString system. PD-L1 expression was evaluated by immunohistochemistry. Patients with durable clinical benefit had a greater infiltration of cytotoxic cells, exhausted CD8, B-cells, CD45, T-cells, CD8 T-cells and NK cells. Immune cell scores such as CD8 T-cell and NK cell were good predictors of durable response with an AUC of 0.82. Among the immune cell markers, XCL1/2 showed the better performance in predicting durable benefit to pembrolizumab, with an AUC of 0.85. Additionally, CD8A, CD8B and EOMES showed a high specificity (>0.86) in identifying patients with a good response to treatment. In the same series, PD-L1 expression levels had an AUC of 0.61. The characterization of tumor microenvironment, even with the use of single markers, can improve patients’ selection for pembrolizumab treatment.

scholarly journals Chemo-immunotherapy as first-line treatment for small-cell lung cancer

2020 ◽  
Vol 12 ◽  
pp. 175883592098036
Author(s):  
Saira Farid ◽  
Stephen V. Liu
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Predictive Biomarkers ◽  
High Response Rate ◽  
Small Cell ◽  
Standards Of Care ◽  
Small Cell Lung ◽  
First Line ◽  
Line Chemotherapy

Small-cell lung cancer (SCLC) is a highly lethal subtype of lung cancer. Despite concerted efforts over the past several decades, there have been limited therapeutic advances. Traditional chemotherapy offers a high response rate and rapid symptomatic improvement, but its benefit is fleeting, and relapse is quick and unforgiving. Immunotherapy has delivered improved outcomes for patients with many cancers and there was compelling rationale for development in SCLC. While initial efforts with cytotoxic T-lymphocyte protein-4 inhibitors failed to improve upon chemotherapy alone, the addition of programmed death ligand-1 (PD-L1) inhibitors to first-line chemotherapy finally provided long-awaited gains in survival. Atezolizumab, when added to carboplatin and etoposide, improved both progression-free survival and overall survival. Durvalumab, when added to platinum plus etoposide, similarly improved OS. Biomarker development has stalled as PD-L1 expression and tumor mutational burden have not been useful predictive biomarkers. However, based on the significant survival improvements, both atezolizumab and durvalumab were approved by the US Food and Drug Administration to be given with first-line chemotherapy, and these regimens represent the new standards of care for SCLC.

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