Challenging the recalcitrant disease—developing molecularly driven treatments for small cell lung cancer

Mak, Daisy Wing-san; Su, Li; Minchom, Anna

doi:10.1016/j.ejca.2019.04.037

Cited by 22 publications

(17 citation statements)

References 168 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Albeit the magnitude of the effect may be deemed relative if compared to other settings and other diseases (namely NSCLC), the OS survival rates at 12-, 18-, and 24-months (50.2%, 32.0%, 22.3%, respectively) sustain the introduction of these regimens in the standard of care of ES SCLC patients. Further steps in the comprehension of SCLC biology will hopefully shed light on which patients derive the largest benefits from chemo-immunotherapy combinations [42]. After decades, these latter represent the novel standard of care for the treatment of ES SCLC and should be considered the benchmark for the development of even better treatment strategies.…”

Section: Discussionmentioning

confidence: 99%

Adding PD-1/PD-L1 Inhibitors to Chemotherapy for the First-Line Treatment of Extensive Stage Small Cell Lung Cancer (SCLC): A Meta-Analysis of Randomized Trials

Facchinetti

Maïo

Tiseo

2020

Cancers

View full text Add to dashboard Cite

Survival outcomes in extensive-stage small cell lung cancer (ES SCLC) are dismal, with median overall survival (OS) less than 12 months. The combination of PD-1/PD-L1 immune checkpoint inhibitors (ICIs) with first-line platinum-etoposide chemotherapy has been recently evaluated in randomized clinical trials. We performed a systematic literature review through PubMed and conference proceedings. Randomized trials evaluating chemotherapy +/− PD-1/PD-L1 ICIs were included in the meta-analysis. Efficacy (OS), activity [progression-free survival (PFS) and objective response rate (ORR)] outcomes and toxicities were analyzed. For selected endpoints, we focused on patients’ subgroups (OS) and on landmark analyses (OS, PFS). Four randomized trials were identified; globally, 1553 patients were randomized to receive chemotherapy +/− PD-1/PD-L1 ICIs. Adding a PD-1/PD-L1 ICI to chemotherapy led to a significant benefit in OS [hazard ratio (HR) 0.76, 95% confidence interval (CI) 0.68–0.85, p < 0.00001), PFS [HR 0.75, 95% CI 0.68–0.84, p < 0.00001] and ORR [odds ratio 1.28, 95% CI 1.04–1.57, p = 0.02]. No unexpected toxicity emerged. At 12, 18, 24 months for OS, and at 12, 18 months for PFS, experimental arms retained significant improvement in event-free rates, with absolute gain of approximately 10% compared with standard treatment. Albeit the magnitude of the benefit is less impacting compared to other settings of immunotherapy, the addition of PD-1/PD-L1 ICIs to chemotherapy in ES SCLC provided significant improvements in survival outcomes with the known toxicity profile. Biomarkers predicting which patients are suitable to derive long-term benefits are eagerly awaited.

show abstract

Section: Discussionmentioning

confidence: 99%

Adding PD-1/PD-L1 Inhibitors to Chemotherapy for the First-Line Treatment of Extensive Stage Small Cell Lung Cancer (SCLC): A Meta-Analysis of Randomized Trials

Facchinetti

Maïo

Tiseo

2020

Cancers

View full text Add to dashboard Cite

show abstract

“…Currently, immunotherapy by immune checkpoint inhibitor (ICI) has emerged as a crucial therapeutic option for improving the prognosis of various cancers [3][4][5][6][7][8]. This has demonstrated promising efficacy of treatment over conventional chemotherapy for different malignant tumors [9][10][11][12][13][14], including HCC [15,16], by triggering the antitumor immune response of T cells instead of directly targeting the tumor itself [17]. However, the rates of objective response to immune checkpoint inhibitors vary from person to person.…”

Section: Introductionmentioning

confidence: 99%

Assessing PD-L1 Expression Level via Preoperative MRI in HCC Based on Integrating Deep Learning and Radiomics Features

et al. 2021

View full text Add to dashboard Cite

To assess if quantitative integrated deep learning and radiomics features can predict the PD-L1 expression level in preoperative MRI of hepatocellular carcinoma (HCC) patients. The data in this study consist of 103 hepatocellular carcinoma patients who received immunotherapy in a single center. These patients were divided into a high PD-L1 expression group (30 patients) and a low PD-L1 expression group (73 patients). Both radiomics and deep learning features were extracted from their MRI sequence of T2-WI, which were merged into an integrative feature space for machine learning for the prediction of PD-L1 expression. The five-fold cross-validation was adopted to validate the performance of the model, while the AUC was used to assess the predictive ability of the model. Based on the five-fold cross-validation, the integrated model achieved the best prediction performance, with an AUC score of 0.897 ± 0.084, followed by the deep learning-based model with an AUC of 0.852 ± 0.043 then the radiomics-based model with AUC of 0.794 ± 0.035. The feature set integrating radiomics and deep learning features is more effective in predicting PD-L1 expression level than only one feature type. The integrated model can achieve fast and accurate prediction of PD-L1 expression status in preoperative MRI of HCC patients.

show abstract

“…Small cell lung cancer (SCLC) has been identified as a “recalcitrant” disease for its dismal prognosis and limited treatment options 1 . Most SCLC cases have metastatic diseases at diagnosis, with a 5‐year overall survival (OS) rate of less than 10% 1,2 . Even with a high response rate of approximately 70% to first‐line etoposide and platinum‐based chemotherapy, most patients relapse within 6 months, resulting in a median OS of within 1 year 3 …”

Section: Introductionmentioning

confidence: 99%

The combination of pretreatment prognostic nutritional index and neuron‐specific enolase enhances prognosis predicting value of small cell lung cancer

Wang

Shi

et al. 2020

Clinical Respiratory J

View full text Add to dashboard Cite

Introduction Tumor and immune‐inflammatory biomarkers have been demonstrated to be closely associated with cancer prognosis. Objective The present study aims to assess the prognostic value of pretreatment prognostic nutritional index (PNI), carcinoembryonic antigen (CEA), and neuron‐specific enolase (NSE) in small cell lung cancer (SCLC). Methods A retrospective analysis of 301 SCLC patients treated with platinum‐based chemotherapy was performed. Overall survival (OS) was assessed by Kaplan–Meier and multivariate Cox hazard analyses. Results The median OS for total cases was 15.0 months. On univariate analysis, tumor stage (P < 0.001), pretreatment PNI (P < 0.001), CEA (P = 0.039), NSE (P = 0.010), distant metastasis numbers (P < 0.001), and thoracic radiotherapy (P < 0.001) were found to be the predictors of OS. Multivariate analysis showed limited stage, high PNI, NSE < 15 μg/L, and chemoradiotherapy were positive independent prognostic factors (P < 0.05). Low PNI and NSE ≥ 15 μg/L were closely correlated with a high tumor burden status. Three cohorts of SCLC with significant different survival outcomes were divided based on variable PNI and NSE levels. Patients with high PNI and NSE < 15 μg/L showed the best OS of 24.5 months, while patients with low PNI and NSE ≥ 15 μg/L had the worst survival outcome of 10.0 months. Patients with low PNI and NSE < 15 μg/L or high PNI and NSE ≥ 15 μg/L had the similar outcome of 16.5 and 17.0 months, respectively. Conclusions Pretreatment PNI and NSE were independent prognostic factors of SCLC. The combination of PNI and NSE enhanced the OS predicting ability, and patients with high PNI and NSE < 15 μg/L had the best survival outcome.

show abstract

Challenging the recalcitrant disease—developing molecularly driven treatments for small cell lung cancer

Cited by 22 publications

References 168 publications

Adding PD-1/PD-L1 Inhibitors to Chemotherapy for the First-Line Treatment of Extensive Stage Small Cell Lung Cancer (SCLC): A Meta-Analysis of Randomized Trials

Adding PD-1/PD-L1 Inhibitors to Chemotherapy for the First-Line Treatment of Extensive Stage Small Cell Lung Cancer (SCLC): A Meta-Analysis of Randomized Trials

Assessing PD-L1 Expression Level via Preoperative MRI in HCC Based on Integrating Deep Learning and Radiomics Features

The combination of pretreatment prognostic nutritional index and neuron‐specific enolase enhances prognosis predicting value of small cell lung cancer

Contact Info

Product

Resources

About