scholarly journals Anti-PD-1/PD-L1 Therapy for Non-Small-Cell Lung Cancer: Toward Personalized Medicine and Combination Strategies

2018 ◽  
Vol 2018 ◽  
pp. 1-17 ◽  
Author(s):  
Hongshu Sui ◽  
Ningxia Ma ◽  
Ying Wang ◽  
Hui Li ◽  
Xiaoming Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Targeted Therapy ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Diagnostic Assays ◽  
Programmed Death ◽  
Companion Diagnostic ◽  
Nsclc Patients

Lung cancer remains a leading cause of cancer-related mortality worldwide with the poor prognosis. Encouragingly, immune checkpoint blockade targeting programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) has dramatically changed the landscape for treatments in patients with non-small-cell lung cancer (NSCLC). However, only a small proportion of NSCLC patients responded to monotherapy of anti-PD-1/PDL1 agents; together, the development of resistance to anti-PD-1/PD-L1 therapy that leads to failure of anti-PD-1/PD-L1 therapy has significantly limited a broad applicability of the findings in clinical practices. Nowadays, several companion diagnostic assays for PDL1 expression have been introduced for identifying patients who may benefit the immunotherapy. In addition, results from clinical trials explored combinatory therapeutic strategies with conventional and/or targeted therapy reported a higher efficacy with an acceptable safety profile in NSCLC treatments, as compared to the monotherapy of these agents alone. In this review article, we summarized several anti-PD-1/PD-L1 agents licensed for NSCLC treatment, with a focus on predictive biomarkers and companion diagnostic assays for identification of NSCLC patients for immunotherapy anti-PD-1/PDL1 antibodies. Of a great interest, potentials of the combinatory therapy of anti-PD-1/PDL1 therapy with a conventional or targeted therapy, or other immunotherapy such as CAR-T cell therapy were emphasized in the article.

Updated outcomes of previously irradiated non-small-cell lung cancer (NSCLC) patients (pts) receiving programmed death 1 (PD-1) inhibitors.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. e15158-e15158
Author(s):  
Maria Bassanelli ◽  
Diana Giannarelli ◽  
Biagio Ricciuti ◽  
Valentina Magri ◽  
Fabiana Letizia Cecere ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Nsclc Patients

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.

scholarly journals Evaluation of the Lung Immune Prognostic Index in Non-Small Cell Lung Cancer Patients Treated With Systemic Therapy: A Retrospective Study and Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Litang Huang ◽  
Hedong Han ◽  
Li Zhou ◽  
Xi Chen ◽  
Qiuli Xu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Targeted Therapy ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Systemic Therapy ◽  
Meta Analysis ◽  
Prognostic Index ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

The lung immune prognostic index (LIPI) has been shown to be an important prognostic marker for various tumors. However, the prognostic value of LIPI among non-small cell lung cancer (NSCLC) patients treated with systemic therapy remains controversial. We aimed to evaluate survival status according to LIPI among NSCLC patients receiving different forms of systemic therapy at our institution. We also performed a meta-analysis of articles from PubMed and Embase to illustrate this question. For our cohort, we found that good LIPI was associated with better overall survival (OS) among 91 patients on immunotherapy, 329 patients on targeted therapy, and 570 patients on chemotherapy. For the meta-analysis, a total of eight studies with 8,721 patients were included. Pooled results showed that a higher LIPI (those with 1 or 2 factors) was associated with poor overall progression-free survival (PFS) (hazard ratio [HR], 1.57; 95% confidence interval [CI], 1.45−1.71) and OS (HR, 2.01; 95% CI, 1.75−2.31). Subgroup analyses showed that a higher LIPI was related to poor survival among patients prescribed different systemic therapies: immunotherapy (OS HR, 2.50; 95% CI, 1.99–3.13; PFS HR, 1.77; 95% CI, 1.56–2.01), chemotherapy (OS HR, 1.58; 95% CI, 1.34–1.86; PFS HR, 1.38; 95% CI, 1.23–1.55), and targeted therapy (OS HR; 2.15, 95% CI, 1.57–2.96; PFS HR, 1.60; 95% CI, 1.25–2.06). The study shows that the LIPI is a clinically significant prognostic factor for NSCLC patients receiving systemic therapy.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD420209009.

Pneumonitis in non-small cell lung cancer (NSCLC) patients treated with programmed death 1 (PD1) axis inhibitors.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. 9030-9030 ◽  
Author(s):  
Scott N. Gettinger ◽  
Xuchen Zhang ◽  
Robert Homer ◽  
Jennifer Possick ◽  
Anna Wurtz ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Nsclc Patients

scholarly journals TARGETED THERAPY OF NON-SMALL-CELL LUNG CANCER PATIENTS: MOST COMMON ADVERSE EVENTS AND METHODS OF THEIR CORRECTIONS

2017 ◽  
Vol 22 (6) ◽  
pp. 300-306
Author(s):  
Elena V. Reutova ◽  
K. P Laktionov ◽  
M. S Ardzinba
Keyword(s):  
Lung Cancer ◽  
Targeted Therapy ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Serious Adverse Events ◽  
Long Term Treatment ◽  
Nsclc Patients

Major advances in the treatment of non-small-cell lung cancer (NSCLC) patients are associated with the targeted therapy. It is both highly effective in the presence of activating mutations in the tumor and generally well-tolerated. Serious adverse events are recorded much less than with chemotherapy. There are significant differences in the toxicity profile. Both early detection and proper and timely correction of complications of targeted therapies are necessary for the successful long-term treatment of metastatic NSCLC patients.

scholarly journals PD-L1 Polymorphism Can Predict Clinical Outcome of Brazilian Non-Small Cell Lung Cancer Patients After Postoperative Adjuvant Treatment

2020 ◽  
Author(s):  
Juliana Machado-Rugolo ◽  
Tabatha Gutierrez Prieto ◽  
Alexandre Todorovic Fabro ◽  
Edwin Roger Parras Cuentas ◽  
Vanessa Karen Sá ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Outcome ◽  
Small Cell Lung Cancer ◽  
Cell Carcinoma ◽  
Cell Lung Cancer ◽  
Adjuvant Treatment ◽  
Small Cell ◽  
Small Cell Lung ◽  
Programmed Death ◽  
Nsclc Patients

Abstract BackgroundAlthough the incidence and mortality of non-small cell lung cancer (NSCLC) remains high with poor prognosis, programmed death‐1 (PD‐1) and programmed death‐ligand 1 (PD‐L1) pathway are promising prognostic and predictive biomarker of NSCLC. The polymorphisms on PD‐L1 gene may be associated with their protein expressions and affect the adjuvant treatment and outcome of NSCLC patients. The goal of this study was to evaluate the clinicopathologic values of PD-L1 expression and single-nucleotide polymorphisms (SNPs) in the PD-L1 gene in lung adenocarcinoma (ADC), squamous cell carcinoma (SqCC), and large cell carcinoma (LCC). MethodsThe 70 NSCLC samples consisted of 33 samples of ADC, 24 of SqCC and 13 of LCC. All tissue microarray paraffin blocks were used for PD-L1 multiplex immunofluorescence assays with Cell Signaling E1L3N clone. Fifteen polymorphisms in the PD-L1 gene were investigated by deep targeted sequencing.ResultsThe PD-L1 expression was higher in ADC than in SqCC and LCC. Three polymorphisms rs4742098, rs4143815, and rs7041009 were significantly associated with tumor recurrence (P=0.01; P=0.05; P=0.02, respectively). According to the recurrence of the disease, carriers of the G allele were less likely to relapse (P=0.01) compared to the homozygous AA genotype for rs4742098. As in rs4143815, individuals with the C allele were also less likely to relapse (P=0.05). As for rs7041009, individuals with AG or GG genotypes were more likely to relapse. The G allele of rs7041009 also showed a significant correlation with age, younger patients, 16 (41.0%) and status, among 11 (39.3%) compared to carriers of the A allele (P=0.02 and P<0.01, respectively). The rs7041009 AG genotype was inversely associated with E1L3N clone PD-L1 labeling in NSCLCs but did not reach statistical significance. Kaplan-Meier survival curves showed that the prognosis of patients with NSCLC was strongly dependent on the alternative allele G (genotype AG or GG) of rs4742098, alternative allele C (genotype CG or CC) of rs4143815 and individuals with GG genotype of rs7041009 (P=0.02; P=0.05 and P<0.01, respectively). Multivariate analysis by the Cox Regression model showed genotype GG of rs7041009 independently associated with cancer recurrence and patients without adjuvant radiotherapy (hazard ratio [HR] = 7.59, 95% confidence interval [CI] = 1.06-54.03, and HR = 9.24, CI = 1.13-75.16).ConclusionsPD-L1 rs7041009 GG polymorphisms may be useful for the prediction of clinical outcome of radiotherapy in NSCLC. Further studies are needed to confirm our findings and to understand the role of PD-L1 in the radiotherapy outcome of NSCLC patients.

scholarly journals Pretreatment platelet/lymphocyte ratio (PLR) is a significant predictive marker for EGFR targeted therapy in patients with non-small-cell lung cancer

2019 ◽  
Author(s):  
Kejun Liu ◽  
Weiwei Zhang ◽  
Qinquan Tan ◽  
Guanming Jiang ◽  
Jun Jia
Keyword(s):  
Lung Cancer ◽  
Targeted Therapy ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Lymphocyte Ratio ◽  
Platelet Lymphocyte Ratio ◽  
Nsclc Patients ◽  
Egfr Tkis

Abstract Non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) gene mutation is benefited from targeted therapy. There is no other superior predictive factor for targeted therapy except EGFR in the clinical. In this study, we analyzed the effect of pretreatment platelet/lymphocyte ratio (PLR) in NSCLC patients. In the present study, a total of 96 patients with EGFR mutations were included in this study. All patients received EGFR targeted therapy, until disease progression, unacceptable toxicity or other factors. The following evaluation was conducted about 3 days before initial treatment: detailed clinical history, physical examination, radiographic results, pathological diagnosis and laboratory parameters including complete blood cell counts and albumin levels. We found that pretreatment PLR is significantly associated to the PFS of NSCLC patients with EGFR targeted therapy. Patients in the PLR ≥190 group had shorter PFS than those in the PLR <190 group (P= 0.009). Furthermore, the 1-year PFS rate in the PLR ≥190 group were inferior to the low value group (P= 0.016). Multivariate analysis confirmed the role of PLR on predicting the efficacy of targeted therapy for advanced NSCLC. In addition, we found that PLR was also an predictive biomarker for grade 3/4 adverse events of diarrhea. In conclusion, high pretreatment PLR was an independent indicator for predicting a poor PFS for NSCLC patients receiving EGFR-TKIs treatment. Further studies are needed to identify the impact of PLR on results of EGFR-TKIs treatment.

Effects of a mucosal coating spray in non-small cell lung cancer patients with nasal mucositis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21160-e21160
Author(s):  
Fang Wang ◽  
Hui Liu ◽  
Zhen Zeng ◽  
Shasha Wang ◽  
Haifeng Qin
Keyword(s):  
Lung Cancer ◽  
Targeted Therapy ◽  
Small Cell Lung Cancer ◽  
Oral Mucositis ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Oral Liquid ◽  
Nsclc Patients

e21160 Background: Targeted therapy opens a new era in the treatment of non-small cell lung cancer (NSCLC). At the same time, it also faces a serious problem, that is, the adverse events brought by new drugs, which not only affect the quality of patients’ life, but may even endanger their lives. Nasal mucositis (NM) may cause significant discomfort for the patients, and even result in the interruption of treatment. Episil (mucosal coating spray) oral liquid is a preservative-free oral liquid gel that can be used for the management of pain associated with oral lesions of various etiologies. Our study prospectively assessed effects of mucosal coating spray oral liquid in NSCLC patients with NM. There is no similar studies at home and abroad. Methods: Our study enrolled 15 patients who experience nasal mucositis after targeted therapy (Table). We designed a specific questionnaire according to Oral Mucositis Daily QuestionnaireOMDQ), Oral Mucositis Assessment Scale (OMAS), and the Patient-Reported Oral Mucositis Symptom (PROMS) to evaluate the change of life quality in NSCLC patients. All the patients needed to complete the questionnaire included in the statistical analysis. Evaluations were made before and after 5 treatment days. Results: All the patients were evaluated. Among patients, 87% suffered from NM grade 2 and 33% were with bleeding at study start, quality of life scores improved significantly after 5 treatment days with mucosal coating spray. Only 1 patient’s pain score reduced not that well because of nonstandard medication. No drug-related adverse reactions were found. Conclusions: Mucosal coating spray can effectively improve the nasal mucositis caused by targeted therapy in NSCLC patients. It may provide a new and effective therapy strategy for them, but large sample and additional clinical trials are also needed, especially for bevacizumab as one agent of combination protocol.

scholarly journals Development of a Companion Diagnostic for Pembrolizumab in Non–Small Cell Lung Cancer Using Immunohistochemistry for Programmed Death Ligand-1

2016 ◽  
Vol 140 (11) ◽  
pp. 1243-1249 ◽  
Author(s):  
Marisa Dolled-Filhart ◽  
Charlotte Roach ◽  
Grant Toland ◽  
Dave Stanforth ◽  
Malinka Jansson ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Cutoff Score ◽  
Small Cell Lung ◽  
Programmed Death Ligand 1 ◽  
Immunohistochemical Assay ◽  
Programmed Death ◽  
Companion Diagnostic

Context.— Programmed death ligand-1 (PD-L1) expression by tumors may enable them to avoid immunosurveillance. Objective.— To develop a PD-L1 immunohistochemical assay using the 22C3 anti–PD-L1 murine monoclonal antibody on the Dako platform as a possible companion diagnostic for pembrolizumab in patients with non–small cell lung cancer. Design.— Tumor samples from 146 patients with non–small cell lung cancer treated with pembrolizumab in KEYNOTE-001 and for whom response data were available were scored according to their staining intensity by a single pathologist using 4 methods: percentage of tumor cells staining at any intensity (PS1), moderate/strong intensity (PS2), strong intensity (PS3), and H-score (PS1 + PS2 + PS3). The cutoff score for predicting response to pembrolizumab was determined using receiver operating characteristic analysis. Progression-free and overall survival were assessed in patients with measurable disease per Response Evaluation Criteria in Solid Tumors, version 1.1 (n = 146). Results.— The 4 scoring methods assessed performed similarly; PS1 with a 50% cutoff score is the simplest and easiest method to implement in practice. Response to pembrolizumab was observed in 19 of 44 patients (43%) with a PS1 score of 50% or higher and 8 of 102 patients (8%) with PS1 lower than 50% (odds ratio, 8.93). Median progression-free and overall survival was 4.0 months and not yet reached, respectively, for patients with a PS1 of 50% or higher, and 2.1 and 6.1 months, respectively, for those with PS1 lower than 50%. Conclusion.— The PD-L1 immunohistochemical assay shows the potential for enrichment of trial populations and as a companion diagnostic tool in non–small cell lung cancer.

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