scholarly journals 466 Use of a 27-gene immuno-oncology (IO) assay to associate response to single-agent immune checkpoint inhibitor (ICI) therapy in advanced-stage NSCLC patients from a large Canadian cohort

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A495-A495
Author(s):  
David Saltman ◽  
Nicole Croteau ◽  
Heather Lockyer ◽  
Rob Seitz ◽  
Frank McMahon ◽  
...  

BackgroundLung cancer is the leading cause of cancer-related deaths worldwide. The advent of ICIs specifically targeting programmed cell death protein-1 (PD-1), or its ligand (PD-L1) represents a major therapeutic advance that is now included in standard of care regimens for non-small-cell-lung cancer (NSCLC). PD-L1 expression measured by immunohistochemistry (IHC) staining is the current gold standard predictive biomarker for immune checkpoint inhibitor (ICI) therapy in NSCLC, however many factors beyond PD-L1 expression alone affect the outcome of ICI therapy. Evaluation of other factors to better inform clinical practice will reduce both the potential for adverse immune-related toxicities and expenditure on ineffective costly therapies while potentially identifying patients otherwise missed by PD-L1 staining. The 27-gene IO assay is a RT-qPCR based gene expression panel1 that was developed to classify the tumor immune microenvironment (TIME). It has been shown to be associated with response to ICI therapy in multiple tumor types including triple negative breast cancer, metastatic urothelial carcinoma, and NSCLC where the association was independent of PD-L1 status in patients treated either with monotherapy or combination therapy.2 Currently, BC Cancer measures PD-L1 status by IHC using the PD-L1 22C3 PharmDx assay and reports the tumor proportional score (TPS) to inform clinical decision. Patients with a TPS ≥ 50% may be eligible for first-line treatment with ICI monotherapy and those with < 50% TPS are eligible for second line or later ICI monotherapy. We established this retrospective study of ICI monotherapy treated NSCLC patients to assess the 27-gene IO assay as an informative biomarker for NSCLC ICI treatment decisions.MethodsThis retrospective study is utilizing the BC Cancer Study Database to select approximately 150 patients with stage IIIB or IV NSCLC treated with single-agent ICI therapy across four BC Cancer centers from 2017 forward (figure 1). Patients are selected based on availability of adequate biopsy specimens (FFPE with at least 20% tumor content), availability of PD-L1 IHC results or sufficient tissue to conduct staining, and for whom outcome data is available via chart review. RNA from patient samples is isolated from FFPE biopsies (either primary or metastatic sites) and those that yield ≥50ng RNA will be analyzed by the 27-gene IO assay 1 to derive IO scores (IO positive or IO negative) based on previously defined thresholds.3 The association between patient outcomes on ICI monotherapy and IO scores and PD-L1 IHC will be reported and compared.Abstract 466 Figure 1Schematic representation of patient workflow forReferencesSaltman, A, et al. Prostate cancer biomarkers and multiparametric MRI: is there a role for both in prostate cancer management? Ther Adv Urol 2021;13: 1756287221997186.Ranganath HJA, Smith JR, et al. One-year progression-free survival in lung cancer patients treated with immune checkpoint inhibitors is significantly associated with a novel immunomodulatory signature but not PD-L1 staining. in SITC. Journal Immunotherapy Cancer. 2019.Nielsen, TJ, et al. A novel immuno-oncology algorithm measuring tumor microenvironment to predict response to immunotherapies. Heliyon 2021;7(3):e06438.Ethics ApprovalThe University of British Columba BC Cancer Research Ethics Board Chair, Vice-Chair or second Vice-Chair, has reviewed the above described research project, including associated documentation, and finds the research project acceptable on ethical grounds for research involving human subjects. All participants have provided informed consent before taking part in the study. REB Number H20-02635.

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Jeong Yun Jang ◽  
Su Ssan Kim ◽  
Si Yeol Song ◽  
Yeon Joo Kim ◽  
Sung-woo Kim ◽  
...  

Abstract Background Immunotherapy has been administered to many patients with non-small-cell lung cancer (NSCLC). However, only few studies have examined toxicity in patients receiving an immune checkpoint inhibitor (ICI) after concurrent chemoradiotherapy (CCRT). Therefore, we performed a retrospective study to determine factors that predict radiation pneumonitis (RP) in these patients. Methods We evaluated the size of the planning target volume, mean lung dose (MLD), and the lung volume receiving more than a threshold radiation dose (VD) in 106 patients. The primary endpoint was RP ≥ grade 2, and toxicity was evaluated. Results After CCRT, 51/106 patients were treated with ICI. The median follow-up period was 11.5 months (range, 3.0–28.2), and RP ≥ grade 2 occurred in 47 (44.3%) patients: 27 and 20 in the ICI and non-ICI groups, respectively. Among the clinical factors, only the use of ICI was associated with RP (p = 0.043). Four dosimetric variables (MLD, V20, V30, and V40) had prognostic significance in univariate analysis for occurrence of pneumonitis (hazard ratio, p-value; MLD: 2.3, 0.009; V20: 2.9, 0.007; V30: 2.3, 0.004; V40: 2.5, 0.001). Only V20 was a significant risk factor in the non-ICI group, and MLD, V30, and V40 were significant risk factors in the ICI group. The survival and local control rates were superior in the ICI group than in the non-ICI group, but no significance was observed. Conclusions Patients receiving ICI after definitive CCRT were more likely to develop RP, which may be related to the lung volume receiving high-dose radiation. Therefore, several factors should be carefully considered for patients with NSCLC.


Author(s):  
Misty Dawn Shields ◽  
Julian A. Marin-Acevedo ◽  
Bruna Pellini

The treatment paradigm for patients with advanced non–small cell lung cancer has substantially changed with the discovery of immunotherapy. The incorporation of immunotherapy into treatment algorithms has resulted in better outcomes for patients, with fewer side effects compared with classic chemotherapeutic agents. Multiple treatment options are now available for patients with advanced non–small cell lung cancer, ranging from single-agent immunotherapy to quadruple therapy, which involves dual immune checkpoint inhibitor plus chemotherapy or immune checkpoint inhibitor plus chemotherapy plus anti–vascular endothelial growth factor drugs. This article will review landmark studies that have led to U.S. Food and Drug Administration approval of immunotherapy agents alone or in combination with chemotherapy or other immunotherapy drugs to treat advanced non–small cell lung cancer.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Osamu Nishiyama ◽  
Shigeki Shimizu ◽  
Koji Haratani ◽  
Kosuke Isomoto ◽  
Junko Tanizaki ◽  
...  

Abstract Background The utility of bronchoscopy for patients with suspected immune checkpoint inhibitor (ICI)-related pneumonitis is currently debatable. The purpose of this study was to examine the findings of bronchoalveolar lavage (BAL) analysis and transbronchial lung biopsy (TBLB) in non-small cell lung cancer (NSCLC) patients with ICI-related pneumonitis, and to elucidate the clinical significance of bronchoscopy for this health condition. Patients and methods Consecutive NSCLC patients treated with ICIs, diagnosed with ICI-related pneumonitis after undergoing bronchoscopy between October 2015 and March 2019 were retrospectively screened. Findings of BAL fluid analysis and/or TBLB specimen histology were reviewed. Results Twelve patients underwent bronchoscopy for the diagnosis of ICI-related pneumonitis, ten of whom underwent BAL. An increase in the proportion of lymphocytes higher than 20% was observed in all ten patients. An increase in the proportion of neutrophils (> 10%) and eosinophils (> 10%) was observed in two and one patient, respectively. TBLB specimens were analyzed for eight patients. Major histologic findings included alveolitis in seven (87.5%) and organizing pneumonia (OP) in five (62.5%) patients. Other findings included acute lung injury and fibrosis. All twelve patients demonstrated favorable outcomes. Conclusion A major characteristic of BAL analysis in ICI-related pneumonitis with NSCLC was an increased proportion of lymphocytes. The histologic features of lung tissue included alveolitis and/or OP. Acute lung injury and fibrosis were observed. Although the necessity of bronchoscopy should be determined on a case-by-case basis, it is necessary to assess these parameters when proper differential diagnosis is needed.


2021 ◽  
Author(s):  
Jeong Yun Jang ◽  
Su Ssan Kim ◽  
Si Yeol Song ◽  
Yeon Joo Kim ◽  
Sung-woo Kim ◽  
...  

Abstract Background: Immunotherapy has been administered to many patients with non-small-cell lung cancer (NSCLC). However, only few studies have examined toxicity in patients receiving an immune checkpoint inhibitor (ICI) after concurrent chemoradiotherapy (CCRT). Therefore, we performed a retrospective study to determine factors that predict radiation pneumonitis (RP) in these patients.Methods: We evaluated the size of the planning target volume, mean lung dose (MLD), and the lung volume receiving more than a threshold radiation dose (VD) in 106 patients. The primary endpoint was RP ≥ grade 2, and toxicity was evaluated. Results: After CCRT, 51/106 patients were treated with ICI. The median follow-up period was 11.5 months (range, 3.0–28.2), and RP ≥ grade 2 occurred in 47 (44.3%) patients: 27 and 20 in the ICI and non-ICI groups, respectively. None of the examined clinical factors were associated with RP. Four dosimetric variables (MLD, V20, V30, and V40) had prognostic significance in univariate analysis for occurrence of pneumonitis (odds ratio, p-value; MLD: 3.0, 0.026; V20: 4.1, 0.001; V30: 3.1, 0.006; V40: 3.7, 0.002). Only V20 was a significant risk factor in the non-ICI group, and V30 and V40 were significant risk factors in the ICI group. The survival and local control rates were superior in the ICI group than in the non-ICI group, but no significance was observed.Conclusions: Patients receiving ICI after definitive CCRT were more likely to develop RP, which may be related to the lung volume receiving high-dose radiation. Therefore, several factors should be carefully considered for patients with NSCLC.


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