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.

scholarly journals Clinical Characteristics of Osimertinib Responder in Non-Small Cell Lung Cancer Patients with EGFR-T790M Mutation

Cancers ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 365 ◽  
Author(s):  
Akihiro Yoshimura ◽  
Tadaaki Yamada ◽  
Naoko Okura ◽  
Takayuki Takeda ◽  
Kazuki Hirose ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Small Cell ◽  
Small Cell Lung ◽  
T790m Mutation ◽  
Nsclc Patients ◽  
Egfr T790m ◽  
Egfr Tkis

Osimertinib is a mutant-selective EGFR inhibitor that is effective against non-small cell lung cancer (NSCLC) in patients with the EGFR-T790M mutation, who are resistant to EGFR-tyrosine kinase inhibitors (EGFR-TKIs). However, the factors affecting response to osimertinib treatment are unknown. In this retrospective study, 27 NSCLC patients with the EGFR-T790M mutation were enrolled at five institutions in Japan. Among several parameters tested, the progression-free survival (PFS) associated with the initial EGFR-TKIs was positively correlated with the PFS after osimertinib treatment (p = 0.021). The median PFS following osimertinib treatment and the overall survival (OS) were longer in patients who responded to osimertinib than in those who did not (17.7 months versus 3.5 months, p = 0.009 and 24.2 months versus 13.5 months, p = 0.021, respectively). A multivariate analysis demonstrated that the PFS with initial EGFR-TKIs was significantly related to the PFS with osimertinib treatment (p = 0.035), whereas osimertinib response was significantly related to the PFS and OS with osimertinib treatment (p = 0.016 and p = 0.006, respectively). Our retrospective observations indicate that PFS following the initial EGFR-TKI treatment and the response rate to osimertinib might be promising predictors for effective osimertinib treatment in NSCLC patients with the EGFR-T790M mutation.

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.

Surrogates of response to treatment of non-small cell lung cancer with immunotherapy: Toxicity and leukocyte ratios—Experience of a center.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21052-e21052
Author(s):  
Alba Moratiel Pellitero ◽  
Ines Ruiz Moreno ◽  
Mara Cruellas ◽  
Natalia Alonso Marin ◽  
Maitane Ocáriz ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Immune System ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Neutrophil To Lymphocyte Ratio ◽  
Small Cell Lung ◽  
Lymphocyte Ratio ◽  
Nsclc Patients ◽  
Worse Prognosis

e21052 Background: Immunotherapy is proposed as a therapeutic novelty in metastatic non-small cell lung cancer (NSCLC), in many cases already in front line. It presents different adverse effects than traditional schemes, due to the stimulation of the immune system. There is a possible relationship between toxicity and response. Neutrophil-to-lymphocyte ratio (NLR) as a possible predictive factor of response. Objectives: Evaluating the response according to the toxicity degree in NSCLC patients in real clinical practice. Analyze whether pretreatment NLR high patients have a worse prognosis. Methods: Observational, retrospective, analytical, single-center study. HCULB stage IV NSCLC patients with inmunotherapy treatment during 2016-2018. Descriptive and multivariate analysis. Toxicity grade: CTCAE version 4.0. Response assessment: RECIST 2.0 and immunorelated criteria. Toxicity degree and response (global and individualized results according to treatment and histology). Neutrophil-to-lymphocyte ratio and response. Results: N = 43 patients (35 men, 8 women). Average age 64 years. Response: 3 complete response (CR) (toxicity ≥2), 13 partial response (PR) (toxicity ≥1), 13 stable disease (SD), 12 progression (P) (only 4 toxicity and ≤2), 2 not evaluated. Hypothyroidism as the most common irAE. Relationship between toxicity and response: the absence of irAEs conditions worse prognosis p < 0.05. Histology: 25 adenocarcinoma [18 with irAES (1 CR, 7 PR, 8 SD,) and 7 without (1 SD, 5 P, 1 no ev.)]; 17 squamous [13 with irAES (1 CR, 6 PR, 4 SD) and 4 without (3 P, 1 no ev.)]; 1 adenosquamous with irAES and CR. Drug: Atezolizumab N = 8 [6 with irAES (2 PR, 3 SD, 1 P) and 2 without (both P)], Nivolumab N = 16 [9 with irAES (1 CR, 3 PR, 3 SD, 2 P) and 7 without (1 SD, 4 P, 2 no ev.)], Pembrolizumab N = 19 [17 with irAEs (2 CR, 8 PR, 6 SD, 1 P) and 2 without (both P)]. Significant positive correlation between toxicity and response (p < 0.001) R = 0.067, (CI 99% 0.378-0.837), regardless of histology and drug. It is observed a better response in those patients who presented a NRL close to 3 or less at the beginning of treatment. On the contrary, it is observed that subjects with NRL greater than 4 obtained worse results when they were treated with immunotherapy. Conclusions: The appearance of irAES like a response indicator of immune system, seem to conditione better evolution. In contrast, the absence of toxicity predicts a worse prognosis. Further studies with a larger sample are needed to confirm our findings about the predictive value of NLR and optimize therapeutic regimens if necessary.

scholarly journals Predictive molecular markers for EGFR-TKI in non-small cell lung cancer patients: new insights and critical aspects

2010 ◽  
Vol 1 (1) ◽  
pp. 10 ◽  
Author(s):  
Paola Ulivi ◽  
Daniele Calistri ◽  
Wainer Zoli ◽  
Dino Amadori
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Objective Response ◽  
Small Cell ◽  
Correct Selection ◽  
Small Cell Lung ◽  
Nsclc Patients ◽  
Egfr Tkis

In recent years, a number of novel agents have been investigated that target specific molecular pathways in non-small cell lung cancer (NSCLC). A great deal of effort has been focused on identifying specific markers that predict treatment response, given that a tailored approach would maximize both the therapeutic index and the cost-effectiveness. The epidermal growth factor receptor (EGFR) pathway has emerged as a key regulator of cancer cell proliferation and invasion, and several specific EGFR inhibitors have been examined. Gefitinib and erlotinib are selective EGFR tyrosine kinase inhibitors (EGFR-TKIs), demonstrating good results in selected cases both in terms of objective response rate and of overall survival. At present, EGFR gene mutations are the best positive predictive factors for TKI therapy, and a number of other potential biomarkers are being investigated as additional positive or negative predictors of response. The correct selection of patients that could benefit from these innovative therapies, based on an accurate molecular characterization, is mandatory to provide the best clinical management. Currently, the main factor limiting the characterization of metastatic NSCLC patients is the small quantity of tumor cells available for molecular analysis. In this paper we provide an overview of the most important molecular predictive markers for EGFR-TKIs therapy in NSCLC patients, and focus attention on biological samples suitable for analysis and alternative sampling approaches such as plasma- or serum-derived DNA.

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