scholarly journals Association of immune-related pneumonitis with the efficacy of PD-1/PD-L1 inhibitors in non-small cell lung cancer

2020 ◽  
Vol 12 ◽  
pp. 175883592092203
Author(s):  
Pengfei Cui ◽  
Di Huang ◽  
Zhaozhen Wu ◽  
Haitao Tao ◽  
Sujie Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Checkpoint Inhibitor ◽  
Small Cell ◽  
Rank Test ◽  
Small Cell Lung ◽  
Cryptogenic Organizing Pneumonia ◽  
Nsclc Patients

Background: Cutaneous adverse events (AEs) have been positively associated with immune checkpoint inhibitor (ICI) efficacy in patients with melanoma, but little is known regarding the association between checkpoint inhibitor pneumonitis (CIP) and programmed cell death protein 1/programmed death ligand 1 (PD-1/PD-L1) inhibitor efficacy in non-small cell lung cancer (NSCLC). Methods: A single-institution, retrospective medical record review of patients with advanced or recurrent NSCLC who were treated with PD-1/PD-L1 inhibitors between 1 September 2015 and 1 June 2019 was conducted. A total of 276 NSCLC patients with or without immune-related pneumonitis who received at least one dose of ICIs and had at least one follow-up visit were identified. Kaplan–Meier curves of the progression-free survival (PFS) of patients stratified according to immune-related pneumonitis development were evaluated with the log-rank test as a preplanned primary objective. Multivariate analysis of PFS was performed with Cox proportional hazard regression models. Results: In the cohort of 276 patients, 42 patients developed CIP attributed to PD-1/PD-L1 inhibitors. Survival analysis showed that the overall response rate was significantly higher in patients with CIP than in those without CIP (61.90% versus 29.91%, respectively, p < 0.01), and that CIP development was significantly associated with increased PFS (45.80 weeks versus 21.15 weeks, respectively, p < 0.01). Additionally, 16-week landmark analysis produced the same results. Similarly, subgroup analysis of PD-1 inhibitor-treated, nivolumab-treated, and pembrolizumab-treated groups also revealed that CIP increased survival in NSCLC patients. Additionally, grade 1–2 pneumonitis showed an association with increased ICI efficacy in NSCLC; however, grade 3–4 pneumonitis did not. In addition, only two of the four pneumonitis radiological subtypes showed associations with increased ICI efficacy in NSCLC. Conclusion: CIP is associated with enhanced PD-1/PD-L1 inhibitor efficacy in NSCLC patients. Grade 1–2 pneumonitis and the radiological features of hypersensitivity and cryptogenic organizing pneumonia (COP) may be signs of enhanced ICI efficacy. However, further studies with larger numbers of patients and longer follow-up times are needed to validate our findings.

scholarly journals MicroRNA-154 Expression is Associated With The Prognosis in Non-Small Cell Lung Cancer.

2020 ◽  
Author(s):  
Yue Zhao ◽  
Xiangjun Kong ◽  
Hongbing Wang
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Prognostic Indicator ◽  
Small Cell ◽  
Rank Test ◽  
Small Cell Lung ◽  
Lower Survival Rate ◽  
Nsclc Patients ◽  
Low Expression

Abstract Background: MicroRNAs are noncoding RNAs that regulate cellular processes during the progression of tumors. Among various microRNAs, MicroRNA-154 (miR-154) has been reported to be involved in many critical processes of human malignancies. This study aimed to evaluate the significance and prognostic value of miR-154 in human non-small cell lung cancer (NSCLC).Methods: A total of 144 NSCLC tissues samples and matched non-tumor adjacent tissues specimens were obtained from NSCLC patients and the quantitative real-time PCR (qRT-PCR) was performed to investigate expression levels of miR-154. The correlation between miR-154 expression and survival outcomes of NSCLC patients was performed by Kaplan-Meier analysis, univariate and multivariate analysis.Results: MiR-154 expression was significantly decreased in NSCLC tissues compared with that in matched non-tumor adjacent tissues (P<0.001). In addition, low expression of miR-154 was demonstrated to be associated with tumors size, TNM stages and distant metastasis of NSCLC patients Survival analysis revealed that patients with low expression of miR-154 showed significantly lower survival rate for OS, DFS and RFS, respectively (all, log rank test, P<0.001) and miR-154 could be an independent prognostic indicator for NSCLC patients.Conclusion: The results suggest that miR-154 has the clinical significance in the progression of NSCLC and could be a potential prognostic biomarker for NSCLC patients.

Follow up analysis by exosomal miRNAs in EGFR mutated non-small cell lung cancer (NSCLC) patients during osimertinib (AZD9291) treatment: A potential prognostic biomarker tool.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. e23035-e23035 ◽  
Author(s):  
Marco Giallombardo ◽  
Jorge Jorge Chacartegui ◽  
Pablo Reclusa ◽  
Jan P. Van Meerbeeck ◽  
Riccardo Alessandro ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Prognostic Biomarker ◽  
Small Cell ◽  
Small Cell Lung ◽  
Exosomal Mirnas ◽  
Nsclc Patients ◽  
Egfr Mutated

scholarly journals Evaluation of nutritional status in non-small-cell lung cancer: screening, assessment and correlation with treatment outcome

ESMO Open ◽  
2020 ◽  
Vol 5 (3) ◽  
pp. e000689 ◽  
Author(s):  
Ilaria Trestini ◽  
Isabella Sperduti ◽  
Marco Sposito ◽  
Dzenete Kadrija ◽  
Alessandro Drudi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Nutritional Status ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Nutritional Risk ◽  
Rank Test ◽  
Small Cell Lung ◽  
Nrs 2002 ◽  
Nsclc Patients

BackgroundNutritional derangements are common hallmarks of non-small-cell lung cancer (NSCLC). Nevertheless, their early detection is overlooked in clinical routine. This study aimed to evaluate nutritional status and its correlation with outcome in NSCLC patients.MethodsData regarding NSCLC patients undergoing nutritional evaluation were prospectively collected (May 2016–October 2018). Nutritional risk was assessed by Nutritional Risk Screening 2002 (NRS-2002). Bilateral psoas major muscles were measured at L3 vertebrae level with routine staging-computed tomography and changes were evaluated using Wilcoxon signed-rank test. Clinico-pathological and nutritional data were correlated to progression-free/overall survival (PFS/OS) and response rate (ORR) using a Cox and logistic regression model. Kaplan–Meier curves were compared with log-rank test.ResultsThirty-eight patients were included. The majority (65.8%) of them were at nutritional risk (NRS-2002 ≥3). At multivariate analysis for patients with advanced disease, age (HR 2.44, p=0.05), performance status (HR 2.48, p=0.043) and NRS-2002 (HR 1.74, p=0.001) were significant independent predictors for PFS and weight loss (HR 1.07, p=0.008) for OS. Patients with baseline NRS-2002 <3 had significantly longer 1-year PFS (85.7% vs 19.4%, p=0.02) and higher ORR (66.7% vs 21.4%) than those with NRS-2002 ≥3. An explorative evaluation demonstrated that NRS-2002 score significantly decreased after nutritional intervention (p=0.001) for 3 months.ConclusionBaseline nutritional risk represents a prognostic factor in NSCLC. Nutritional counselling should be applied as a fundamental tool to improve nutritional risk in a short period, ameliorating patients’ outcome.

Biomarker utilization in non-small cell lung cancer, are we treating after testing?

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9609-9609
Author(s):  
Elias Makhoul ◽  
Jong Taek Kim ◽  
Wenjuan Zhang ◽  
Jean Raphael Lopategui ◽  
Ani Sarkis Balmanoukian ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Targeted Therapy ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Targeted Therapies ◽  
Small Cell ◽  
Molecular Testing ◽  
Small Cell Lung ◽  
Nsclc Patients

9609 Background: Targeted therapy in EGFR and ALK mutated non-small cell lung cancer (NSCLC) has been the standard of care for nearly a decade with subsequent FDA approvals for ROS1 and BRAF V600 mutated NSCLC occurring in 2016 and 2017. However, recent studies have shown suboptimal utilization of genomic profiling results in these patients. In 1 recent study of community oncologists, ~70% of EGFR/ALK+ patients received appropriate targeted therapy, while patients with other gene mutations (including BRAF and ROS1) only received targeted therapy ~30% of the time. Left unanswered was what patients were receiving instead and why. Additionally, it is unknown if this finding is generalizable to the academic setting. We aimed to investigate whether in our patient population, NSCLC patients with actionable mutations received associated FDA approved therapies and if not why. Methods: The pathology database was queried for all NSCLC with molecular testing (including qPCR, FISH and NGS) from 2009 to 2019. Patients with sensitizing EGFR, ALK, ROS1 or BRAF mutations that were detected after the first FDA approval for their respective targeted therapies were included for analysis with those lost to follow up subsequently excluded. Basic demographic and clinical variables were collected as well as treatment records. Results: 2160 NSCLC patients were evaluated (2160 EGFR, 1417 ALK, 810 ROS1, 589 BRAF). 468 patients were identified with targetable mutations (411 EGFR, 46 ALK, 5 ROS1, 6 BRAF). No patient had more than 1 targetable mutation. Of those patients, 248 were at an advanced stage and had clinical follow up (202 EGFR, 37 ALK, 4 ROS1, 5 BRAF). Of those patients 197/202 (97.5%), 33/37 (89.2%), 3/4 (75%) and 1/5 (20%) received EGFR, ALK, ROS1 or BRAF targeted therapy respectively. Across biomarkers 14/248 patients (5.6%) did not receive subsequent targeted therapy. 10 patients (5 EGFR, 3 ALK, 1 ROS1 and 1 BRAF) passed away before targeted therapy could be initiated. Physician choice and missed findings accounted for the remaining four cases. Conclusions: The vast majority of advanced NSCLC patients analyzed in this study received appropriate targeted therapy matched to genomic findings. The main reason (~4% of total cases) that patients did not receive therapy was due to rapidly progressive disease and death before it could be initiated. These findings are at odds with those published from the community setting. This may be due to multiple factors, including clinician education, ease of access to targeted therapies across patient populations and incomplete data in the previous study populations.

Neutrophil-to-lymphocyte ratio and subsequent recurrence of non-small cell lung cancer patients in remission.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 8533-8533
Author(s):  
Abigail Sy Chan ◽  
Søren Bentzen ◽  
Michael L Adashek ◽  
Joseph Friedberg ◽  
Melissa Culligan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Multivariable Analysis ◽  
Small Cell ◽  
Small Cell Lung ◽  
Lymphocyte Ratio ◽  
Treatment Type ◽  
Nsclc Patients

8533 Background: Baseline neutrophil-lymphocyte ratio (NLR), a surrogate marker for systemic inflammation and immunosuppression, is a well-established prognostic marker in non-small cell lung cancer (NSCLC). This study tests if interim NLR is prognostic in NSCLC patients in remission. Methods: This single-center, retrospective cohort study analyzed 131 NSCLC patients treated from 2010-2015 who achieved complete remission. Patient data included demographics, histologic subtypes, stage, and treatment type. NLR was calculated at baseline and from the first available blood sample during remission. Kaplan-Meier estimates of overall survival (OS) and time to recurrence were compared using the log-rank test for trend. Multivariable analysis was conducted using the Cox proportional hazards model. Results: Of 131 cases, 63 had subsequently recurred at the last follow up. Mean age was 64 ± 10 years. Histology: adenocarcinoma (60%), squamous cell (33%), and unspecified (7%). Ninety percent were smokers. Thirty-five percent had stage I, 24% had stage II, and 41% had stage III disease. Treatment modalities varied from surgery (28%), chemotherapy (2%), or radiation therapy (10%) alone, or combined (50%). The time from end of treatment, median (range), to the interim NLR was 9.2 months (2.2, 66.7). The baseline and interim median NLR were 2.6 (0.6, 34.0) and 3.1 (0.5, 20.5), respectively. The median follow-up duration was 44 months (5.9, 101). For the univariate analysis interim NLR was binned into tertiles. In multivariable analysis remission NLR remained strongly prognostic for OS (P<0.001) as did patient’s age (P=0.002), but not stage, race, sex, and baseline NLR. Conclusions: Our study found that interim NLR, obtained in remission, was strongly prognostic for OS and recurrence. The results may indicate that even subclinical disease promotes immunosuppression or alternatively that immunosuppression increases recurrence risk. NLR during remission may help identify NSCLC patients at high risk of recurrence and may thus be of value in surveillance of lung cancer survivors. [Table: see text]

Soluble biomarker signature to predict outcome of patients with non-small-cell lung cancer (NSCLC) treated with anti-PD1/PDL1 monoclonal antibodies.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20685-e20685
Author(s):  
Javier Garde-Noguera ◽  
Eloisa Jantus-Lewintre ◽  
Sandra Gallach ◽  
Jose Vidal-Martinez ◽  
Ana Blasco ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Monoclonal Antibodies ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Response Rate ◽  
Small Cell ◽  
Rank Test ◽  
Second Line ◽  
Small Cell Lung ◽  
Nsclc Patients

e20685 Background: Immunotherapy with anti-PD1/PDL1 monoclonal antibodies has become the second line standard treatment for most patients diagnosed of advanced Non-Small-Cell lung cancer (NSCLC). The aim of this study is to assess the utility of circulating biomarkers such as sPDL1, sPDL2, sCD137, sIDO, sTIM3, sCD28, sCD27, sCTLA4, sHVEM, sLAG3, sCD80 and sGITR for predicting efficacy of immunotherapy with anti-PD1/PDL1 therapies. Methods: Blood samples were collected before treatment from 50 NSCLC patients who received anti PD1/PDL1 therapies (second line). Plasma biomarkers´ levels were measured by Multiplex bead-based assays. Continuous variables were categorized using the median as a cut-off. Non parametric test were used for correlations between analytical variables and clinical-pathological parameters and response rate analysis. For survival analysis (progression free survival-PFS and overall survival-OS) Kaplan Meier curves and long-rank test were performed. Results: 50 patients met inclusion criteria. Biomarkers associated with better outcome in terms of Response Rate or PFS were sPDL1, sIDO, sCD137 and sGITR. Median plasma levels of sPDL1, sCD137, sIDO and sGITR were 80.5, 168.7, 64.92s and 114.43 ng/ml respectively. ORR was higher in patients with high levels of CD137 (75 vs 25%, p = 0.28), GITR (83.3 vs 16.7%, p = 0.009) and sPDL1 (66.7 vs 33.3%, p = 0.07). Median PFS was significantly higher for patients with high sPDL1 levels (NR vs 3 months, p = 0.017), and there was a favourable trend for patients with higher serum levels of CD137 (NR vs 5.07, p = 0.11), sIDO (NR vs 5.57 months, p = 0.08); and sGITR (14.33 vs 5.57 months, p = 0.16). Combination of these biomarkers allowed the identification of three groups: group1 (0-1 positive biomarker), group2 (2 positive biomarkers) and group 3 (3 or 4 positive biomarkers), with significant differences in ORR (8.3 vs 25 vs 66.7%, p = 0.01), PFS (median 3.2, 1.1 and NR months, p = 0.01) and OS (median 2.3, 5.0 and NR months, p = 0.02). Conclusions: Circulating immune markers can be reliable detected in plasma of advanced NSCLC patients. In patients treated with anti-PD1 antibodies. sCD137, sIDO, sGITR and sPDL1 seem to be related to the degree of response or PFS. Combination of these biomarkers might be helpful to predict efficacy of immunotherapy treatment.

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