scholarly journals Pulmonary Sarcoidosis Activation following Neoadjuvant Pembrolizumab plus Chemotherapy Combination Therapy in a Patient with Non-Small Cell Lung Cancer: A Case Report

2017 ◽  
Vol 10 (3) ◽  
pp. 1070-1075 ◽  
Author(s):  
Ghina Fakhri ◽  
Reem Akel ◽  
Ziad Salem ◽  
Ayman Tawil ◽  
Arafat Tfayli
Keyword(s):  
Lung Cancer ◽  
Combination Therapy ◽  
Lymph Nodes ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Checkpoint Inhibitors ◽  
Pulmonary Sarcoidosis ◽  
Small Cell ◽  
Small Cell Lung ◽  
Immune Mediated

Background: Pembrolizumab is a humanized monoclonal antibody which serves to enhance the antitumor immune response by targeting programmed cell death 1 receptor. The use of pembrolizumab plus carboplatin/pemetrexed combination therapy results in improvement in overall survival and progression-free survival rates for non-small cell lung cancer (NSCLC) patients as compared to chemotherapy alone. However, numerous immune-mediated toxicities of pembrolizumab have been reported. Case Presentation: We report the case of a 74-year-old male patient diagnosed with stage IIIA programmed death-ligand 1-positive non-small cell lung adenocarcinoma treated with 4 cycles of carboplatin/pemetrexed plus pembrolizumab combination therapy followed by 2 cycles of pembrolizumab treatment. Follow-up PET-CT scanning showed a very good response at the level of the tumor but new-onset activity in bilateral hilar and mediastinal lymph nodes. Biopsy of these lymph nodes revealed a benign pathology with noncaseating granulomas consistent with immune-mediated sarcoidosis. Conclusion: The pathogenesis of immunotherapy-induced sarcoidosis is not yet known but has been reported in different cancers and using different checkpoint inhibitors. To our knowledge, this case is the first in the literature displaying pulmonary sarcoidosis in a patient with NSCLC 4 months after having initiated chemotherapy plus pembrolizumab combination therapy.

Exploring Novel Immune-Related Toxicities and Endpoints with Immune-Checkpoint Inhibitors in Non-Small Cell Lung Cancer

2013 ◽  
pp. e280-e285 ◽  
Author(s):  
Laura QM Chow
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Small Cell Lung ◽  
Immune Mediated ◽  
Programmed Death

Because of dramatic tumor regressions reported with the anti-programmed death-1 (PD-1) and anti-programmed death ligand-1 (PDL-1) antibodies inhibiting the PD-1 immune checkpoint, non-small cell lung cancer (NSCLC) is now recognized as an immune-modifiable disease. As responses were observed in smaller numbers in phase I trials, the immunologic profiles and unique toxicities of these agents have not been fully established in NSCLC. Moreover, PD-1 checkpoint inhibitors in development by different companies may demonstrate diverse spectrums of activity and toxicity. Although the cytotoxic T-lymphocyte antigen-4 (CTLA-4) checkpoint inhibitors in earlier phase studies appeared to have less impressive responses in NSCLC, their safety profile has been more broadly defined. The anti-CTLA-4 antibody, ipilimumab, has the best characterized immune-related toxicities (predominantly skin, gastrointestinal, hepatic, and endocrine) and management strategies in melanoma. Despite the lack of studies directly comparing these agents, toxicities from PD-1 inhibition seem milder than those of CTLA-4 inhibition, with distinct toxicities of pneumonitis infrequently observed with the BMS-936558 anti-PD-1 antibody, nivolumamb, and frequent mild infusion reactions reported with the BMS-936559 anti-PDL-1 antibody. As lungs are critical organs often already compromised in NSCLC patients, immune-mediated pneumonitis can cause worrisome morbidity and mortality. Even though immune checkpoint inhibitors are being rapidly developed in a multitude of trials, optimal immune-mediated toxicity management has not been determined, is evolving, and will be further explored. Early diagnosis and symptom management with corticosteroids form the basis of treatment. Assessment of new immune-response criteria and use of primary endpoints of overall survival (OS) will be important in the development of these immunotherapies in NSCLC.

scholarly journals Combination of Immune Checkpoint Inhibitors and Anti-Angiogenic Agents in Brain Metastases From Non-Small Cell Lung Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Likui Fang ◽  
Wuchen Zhao ◽  
Bo Ye ◽  
Da Chen
Keyword(s):  
Lung Cancer ◽  
Combination Therapy ◽  
Brain Metastases ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Small Cell Lung

Brain metastases remain a critical issue in the management of non-small cell lung cancer (NSCLC) because of the high frequency and poor prognosis, with survival rates often measured in just months. The local treatment approach remains the current standard of care, but management of multiple asymptomatic brain metastases always involves systemic therapy. Given that anti-angiogenic agents and immune checkpoint inhibitors (ICIs) both target the tumor microenvironment (TME), this combination therapy has become a promising strategy in clinical practice. Increasing number of preclinical and clinical studies have shown remarkable anti-tumor activity of the combination therapy, but the efficacy in brain metastases is unclear due to the strict selection criteria adopted in most clinical trials. This review briefly summarizes the potential synergistic anti-tumor effect and clinical development of the combination of anti-angiogenic agents and ICIs in NSCLC brain metastases, and discusses the existing challenges and problems.

scholarly journals The Effect of Asymptomatic and/or Treated Brain Metastases on Efficacy of Immune Checkpoint Inhibitors in Metastatic Non–Small Cell Lung Cancer: A Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Sihan Li ◽  
Hongwei Zhang ◽  
Tingting Liu ◽  
Jun Chen ◽  
Jun Dang
Keyword(s):  
Lung Cancer ◽  
Combination Therapy ◽  
Brain Metastases ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Small Cell Lung

BackgroundTo assess the effect of asymptomatic and/or treated brain metastases (BMs) on the efficacy of immune checkpoint inhibitors (ICIs) in metastatic non-small cell lung cancer (NSCLC).Patients and MethodsPubMed, Embase, Cochrane Library, Web of Science, and recent meetings were searched for randomized controlled trials (RCTs). The primary outcomes of interest were overall survival (OS) and progression-free survival (PFS).ResultsSeventeen articles reporting 15 RCTs with 10,358 patients (1,199 with and 9,159 without BMs) were eligible. ICIs were associated with longer OS and PFS than those in chemotherapy either in patients with (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.51–0.82 and HR, 0.60; 95% CI, 0.45–0.79) or without BMs (HR, 0.74; 95% CI, 0.70–0.78 and HR, 0.70; 95% CI, 0.57–0.86); no significant difference in the pooled HRs for OS (Pinteraction = 0.29) and PFS (Pinteraction = 0.37) was observed between the two patient populations. Subgroup analyses revealed that either ICI monotherapy or combination therapy significantly improved OS and PFS compared with those in chemotherapy both for patients with and without BMs. Superior OS benefit from ICI combination therapy than that in monotherapy was observed in patients with BMs (HR, 0.49 vs. 0.81, Pinteraction = 0.005) but not in patients without BMs (HR, 0.71 vs. 0.76, Pinteraction = 0.27).ConclusionThere was no compelling statistical evidence that the efficacy of ICIs in metastatic NSCLC was modified by the presence of asymptomatic and/or treated BMs. Patients with BMs were likely to obtain more OS benefit from ICI combination therapy than that from monotherapy.

Immune-related endocrine toxicities in non-small cell lung cancer: predictors of outcome to checkpoint inhibitors?

2019 ◽  
Author(s):  
Roberta Poli ◽  
Clement Dumont ◽  
Lisa Pietrogiovanna ◽  
Vincent Servois ◽  
Sophie Beaucaire-Danel ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Predictors Of Outcome ◽  
Small Cell Lung

scholarly journals P09.25 Role of Immune Checkpoint Inhibitors (ICPi) in KRAS-Mutated Non-Small Cell Lung Cancer (NSCLC)

2021 ◽  
Vol 16 (3) ◽  
pp. S300-S301
Author(s):  
M. Peravali ◽  
C. Gomes-Lima ◽  
E. Tefera ◽  
M. Baker ◽  
M. Sherchan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Small Cell Lung
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