Neutrophil-lymphocyte radio (NLR) as a possible predictive factor in patients with advanced NSCLC WHO received immunotherapy.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21042-e21042
Author(s):  
Eduardo Richardet ◽  
Luciana Paola Acosta ◽  
Maria gimena Ferreira ◽  
Ignacio Magi ◽  
Rocio tello Alfonso ◽  
...  
Keyword(s):  
General Population ◽  
Predictive Factor ◽  
Statistical Power ◽  
Advanced Nsclc ◽  
Combined Treatment ◽  
Objective Response ◽  
Strong Relationship ◽  
Neutrophil Lymphocyte Ratio ◽  
Platinum Based Chemotherapy ◽  
Number Of Patients

e21042 Background: There exists a strong relationship between cancer and inflammation. For this reason, attempts have been made to identify different biomarkers of inflammation in recent years. The neutrophil - lymphocyte ratio (NLR) a marker of systemic inflammation, and the infiltranting lymphocytes of the tumor stroma (TILs) have been studied by our research team in different tumors, such as melanoma, breast cancer, colon cancer and NSCLC in patient who had recieved tratment with chemotherapy. We could observe that there was a significant relationship beteween DFS and a high NLR on the one hand, and DSF an intense TILs on the other. Our main objective is to evaluate the relationship between the objective response rate (ORR) and the pretreatment NLR in patients with advanced NSCLC who recieved immunotherapy. Our secondary objective is to analyzed the associated between PFS and RNL in patients with advanced NSCLC undergoing immunotherapy. Methods: Patients with diagnosis of advanced-stage NSCLC who recieved only immunotherapy, immunotherapy with another immunomodulator or in combination with platinum-based chemotherapy werw included. All patients had a follow-up of at least 6 months. The cutoff value > or < 3 for the NLR was use to reference. The laboratory control prior to the beginning of treatment was taken, and the ORR was determined using the Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Statistical analysis was performed using dispersion and position measurements, T-Test and Chi Square test. For PFS analysis Kaplan-Meyer was used. The level of significance for the variables was p < 0.05. Results: 41 patients with advanced NSCLC were analyzed. 43.9% (18 pts) recieved immunotherapy alone with nivolumab. 34.14% (14 pts) received a combined treatment (nivo / ipi) and 21.95% (9 pts.), immuno / QT combination (based on platinum). Regarding the histological presentation, 80.48% were adenocarcinoma. 54% (22 pts) had an NLR > 3 and 46% (19 pts) an NLR < 3. The ORR in the general population was 24%. in pts with an NLR < 3, the ORR that was observed was 42% vs. ORR of 9% in pts with NLR > 3 (p: 0.02). These differences were statistically significant. The median PFS was 11.27 months in the general population. As regards RNL, the median PFS were 20.74 vs 5.52 months in favor of pts with an NLR < 3 (p: 0.04). Conclusions: We could conclude that patients with NSCLC and pretreatment NLR < 3, who undergo immunotherapy, had better ORR compared to those with NLR > 3. These differences was statistically significant. Also, we could observe better PFS in patient with NLR < 3. These difference was estatically significant. We will keep working to obtain a greater number of patients. Then we could have a better analysis and statistical power. It is possible that NLR will be a highly useful and easy-to-acces predictive factor, and it could be used in patients with immunotherapy in our daily practice.

scholarly journals 363 Vactosertib and durvalumab as second or later line treatment for PD-L1 positive non-small cell lung cancer: interim result

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A388-A388
Author(s):  
Byoung Chul Cho ◽  
Ki Hyeong Lee ◽  
Ji-Youn Han ◽  
Byoung Yong Shim ◽  
Hye Ryun Kim ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Objective Response Rate ◽  
Immune Checkpoint Inhibitors ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Platinum Based Chemotherapy ◽  
Number Of Patients ◽  
Anti Tumor Activity

BackgroundTargeting transforming growth factor-β (TGF-β) is reported to augment the efficacy of immune checkpoint inhibitors (ICIs) through either enhanced anti-tumor immunity or the correction of tumor microenvironment (TME). Therefore, the combination of vactosertib, a highly selective TGF-β RI kinase inhibitor, and durvalumab is anticipated to improve anti-tumor activity of the ICI. A phase 1b/2a study was conducted to evaluate the combination of vactosertib and durvalumab in patients with advanced NSCLC who progressed after platinum-based chemotherapy.MethodsPatients were treated with vactosertib at a dose of 200 mg twice daily (five days on and two days off) and durvalumab at a dose of 1500 mg every four weeks. Eligible patients were ≥19 years old with good performance status (ECOG 0–1) and have no prior exposure to immune checkpoint inhibitors or other TGF- β R1 kinase inhibitors. The objectives of this analysis were to evaluate the safety, antitumor activity including objective response rate (ORR), duration of response (DOR), and time to response (TTR) as well as circulating pharmacodynamic biomarkers related to TGF-β signaling. Response was assessed per RECIST (v1.1).ResultsBy August 4 2020, twenty-six PD-L1 positive (SP263 assay) patients were analyzed. Median age was 61.5 years (range 48–83), 69.2% were male, median number of previous lines of chemotherapy was 1 (range 1–4), and all patients were PD-L1 positive (15 patients with PD-L1≥25% and 11 patients with PD-L1 1–24%). The most frequently reported treatment-related adverse events (TRAE) were itching (38.5%) and skin rash (34.6%), but no Gr≥3 itching and rash were observed. Each case of the following was reported as Grade 3 TRAEs: adrenal insufficiency, anemia, and pneumonitis; Grade 4 TRAE, CPK increase, was observed in one patient. Objective response rate was 30.8% and 40.0% in patients with PD-L1≥1% and ≥25% respectively. Circulating PAI-1 and CTGF evaluated in 15 patients decreased significantly on Cycle 1 day 5. Ongoing biomarker results will be presented.ConclusionsThe combination of vactosertib and durvalumab has demonstrated a manageable safety profile and encouraging anti-tumor activity as a potential therapeutic strategy in patients with advanced NSCLC. The efficacy outcomes of this combination in a larger number of patients with advanced NSCLC will be followed.Trial RegistrationNCT03732274Ethics ApprovalThe study was approved by Ethics Board of Severance Hospital (4-2018-0892), National Cancer Center (NCC2019-0057), St. Vincent’s Hospital (VC19MDDF0205), and Chungbuk National University Hospital (2019-08-015).

Phase II trial of weekly docetaxel and gemcitabine as first line therapy for patients with advanced non-small cell lung cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17076-17076 ◽  
Author(s):  
G. McNeill ◽  
S. Kalmadi ◽  
M. Davis ◽  
D. Peereboom ◽  
D. J. Adelstein ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Objective Response ◽  
Small Cell ◽  
Weekly Schedule ◽  
Small Cell Lung ◽  
Platinum Based Chemotherapy ◽  
Platinum Doublet

17076 Background: A platinum doublet has been the standard treatment for patients with advanced non-small cell lung cancer (NSCLC) and good performance status. This treatment results in almost a doubling of 1-year survival, along with an improvement in quality of life despite treatment related toxicities. However, platinum based treatment is associated with significant toxicity. Methods: In this trial, we prospectively evaluated a weekly regimen of docetaxel and gemcitabine for advanced NSCLC from December 2001 to January 2005. The endpoints of this study included objective response rate, survival and toxicity. Forty-two patients with previously untreated, advanced NSCLC with PS 0–1 were included. Patients received docetaxel (36 mg/m2) and gemcitabine (600 mg/m2) on days 1,8 and 15 of a 28-day cycle. Responses were assessed every two cycles. Results: The median age was 63 years; with 22 males and 20 females; 67% were >60 years old; and 38 patients had stage IV disease. In the intent-to-treat (ITT) analysis of response, 16 patients had a partial response (38%) and 15 patients had stable disease (36%). The 1-year survival was 48%; median survival for all patients was 11.3 months and the median progression-free survival was 5.1 months. Toxicities (> grade 3) included neutropenia (29%), asthenia (26%), thrombocytopenia (14%), diarrhea (14%), pneumonitis (7%), peripheral neuropathy (5%), peripheral edema (5%), nail changes (2%), and myositis (2%). Conclusions: This study demonstrated that this non-platinum doublet (docetaxel + gemcitabine) given on a weekly schedule for advanced NSCLC was well tolerated with efficacy comparable to platinum based chemotherapy regimens. [Table: see text]

CCTG BR.34: A randomized trial of durvalumab and tremelimumab +/- platinum-based chemotherapy in patients with metastatic (Stage IV) squamous or nonsquamous non-small cell lung cancer (NSCLC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9502-9502 ◽  
Author(s):  
Natasha B. Leighl ◽  
Scott Andrew Laurie ◽  
Glenwood D. Goss ◽  
Brett Gordon Maxwell Hughes ◽  
Martin R. Stockler ◽  
...  
Keyword(s):  
Adverse Events ◽  
Randomized Trial ◽  
Advanced Nsclc ◽  
Smoking Status ◽  
Objective Response ◽  
Stage Iv ◽  
First Line ◽  
Open Label ◽  
Platinum Based Chemotherapy ◽  
Significant Difference

9502 Background: First-line therapy for advanced NSCLC includes PD-1 checkpoint inhibitor (ICI) monotherapy, and in combination with chemotherapy. Combination ICI have also demonstrated better survival compared to chemotherapy (CM-227). In CCTG BR.34, we compared overall survival (OS) in patients with advanced NSCLC receiving first-line durvalumab plus tremelimumab (DT) with or without platinum doublet chemotherapy (CT). Methods: This international, open-label, randomized trial accrued 301 participants from Canada and Australia, with stage IV NSCLC, EGFR/ALK wildtype, ECOG PS 0/1. Patients were randomized to DT for 4 cycles or DT+CT (pemetrexed- or gemcitabine-platinum), with ongoing D or D + pemetrexed (non-squamous) maintenance until disease progression. Stratification factors included histology, stage IVA v. IVB and smoking status. The primary endpoint was OS; secondary endpoints included progression-free survival (PFS), objective response rate (ORR = CR + PR) and adverse events (AEs). Results: At a median follow up of 16.6 months, no significant difference in OS was seen between the two treatment arms, with a median OS of 16.6 months with DT+CT v. 14.1 months with DT, (estimated HR 0.88, 90% CI 0.67-1.16). PFS was significantly improved in the DT+CT arm (stratified HR 0.67, 95% CI 0.52-0.88; medians 7.7 v. 3.2 months). ORR was higher in the DT+CT arm, 28% v. 14%, (odds ratio 2.1, p=0.001). Preplanned subgroup analysis demonstrated no significant differences in treatment outcomes by plasma TMB (<20 v. ≥20 mut/Mb, Guardant OMNI), age, sex, or smoking status. There was a trend to improved OS with DT+CT in the subgroup with PD-L1 TPS≥50%, (HR 0.64, 95% CI 0.40-1.04, p=0.07). Plasma TMB<20 mut/Mb was associated with shorter survival in both treatment groups (HR 1.99, 95% 1.3-3.1). Toxicity was greater in the DT+CT arm, with grade≥3 adverse events in 82% v. 70%, (p=0.02), most commonly dyspnea, nausea and cough. The incidence of immune-related adverse events was similar between arms (colitis 11%, pneumonitis 6%, endocrinopathy 21%). Grade 5 events occurred in 2.7%, (5 with DT+CT, 3 with DT). Conclusions: The addition of CT to first-line DT did not improve OS in advanced NSCLC. CT+DT improved ORR and PFS, and was associated with greater toxicity. No differential effects were seen by PD-L1 TPS nor bTMB. These data suggest that adding chemotherapy to ICI may be beneficial in those with PD-L1 TPS >=50%, and warrant further analysis in independent datasets. Clinical trial information: NCT03057106 .

KRYSTAL-12: A randomized phase 3 study of adagrasib (MRTX849) versus docetaxel in patients (pts) with previously treated non-small-cell lung cancer (NSCLC) with KRASG12C mutation.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS9129-TPS9129
Author(s):  
Tony S. K. Mok ◽  
William E. Lawler ◽  
Merrill Kingman Shum ◽  
Shaker R. Dakhil ◽  
Alexander I. Spira ◽  
...  
Keyword(s):  
United States ◽  
Advanced Nsclc ◽  
Objective Response ◽  
Progression Free Survival ◽  
The United States ◽  
Mapk Signaling ◽  
Concurrent Administration ◽  
Phase 3 ◽  
Platinum Based Chemotherapy ◽  
Patient Reported

TPS9129 Background: Despite significant advances in chemotherapy and immunotherapy for advanced NSCLC, the majority of pts ultimately develop progressive disease associated with poor outcomes. KRAS is a key mediator of the RAS/MAPK signaling cascade that promotes cell growth and proliferation. KRASG12C mutations occur in 14% of NSCLC (adenocarcinoma), and mutations in KRAS are associated with a poor prognosis. Although KRAS has historically been undruggable, recent research into the development of agents that specifically bind mutant KRAS has led to the development of direct inhibitors of KRASG12C. Adagrasib, an investigational agent, is a potent, covalent inhibitor of KRASG12C that irreversibly and selectively binds to and locks KRASG12C in its inactive state. Adagrasib was optimized for favorable pharmacokinetic (PK) properties, including oral bioavailability, long half-life (̃24 h), and extensive tissue distribution. Initial results have demonstrated encouraging antitumor activity and tolerability of adagrasib monotherapy in pts with NSCLC harboring a KRASG12C mutation. Methods: KRYSTAL-12 is a multicenter, randomized Phase 3 study evaluating the efficacy of adagrasib (600 mg BID) vs docetaxel in pts with advanced NSCLC harboring a KRASG12C mutation who have progressed during or after treatment with a platinum-based regimen and an immune checkpoint inhibitor. The study is designed to demonstrate improvement in the dual primary endpoints of progression-free survival (PFS) and overall survival (OS). Secondary endpoints include safety, objective response rate (ORR) per RECIST 1.1, duration of response (DOR), plasma PK parameters of adagrasib, and patient-reported outcomes (PROs). The study will also explore correlations between gene alterations (at baseline and upon development of treatment resistance) and efficacy. Approximately 450 patients will be randomized in a 2:1 ratio to receive adagrasib or docetaxel and will be stratified by region (United States/Canada vs other countries) and sequential vs concurrent administration of prior platinum-based chemotherapy and anti–PD-1/PD-L1 antibody. The planned sample size is sufficiently powered for the hypothesized treatment effect of the endpoints. Pts will receive study treatment until disease progression, unacceptable adverse events, investigator decision to terminate treatment, or patient withdrawal. This study is currently enrolling and will be open at sites in the United States, Europe, and Asia. Clinical trial information: NCT04685135.

Relationship between neutrophils/lymphocytes and tumor infiltrating lymphocytes stroma in patients with invasive muscle bladder cancer and the response to treatment.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16513-e16513
Author(s):  
Martin Eduardo Richardet ◽  
Maria gimena Ferreira ◽  
Martin Paradelo ◽  
Luciana Paola Acosta ◽  
Matias Molina ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Predictive Factor ◽  
Objective Response ◽  
Neoadjuvant Treatment ◽  
High Body Mass Index ◽  
Response To Treatment ◽  
Number Of Patients ◽  
The Difference ◽  
Tract Infections ◽  
Infiltrating Lymphocytes

e16513 Background: The bladder cancer is a malignant disease. It has been related to tobacco consumption, fat diet, high body mass index (BMI) and urinary tract infections. As a result of the activation the pro-inflammatory pathways. Neutrophil to lymphocyte radio (NLR) and the infiltrating lymphocytes of the tumor stroma (TILs) have been shown to have a significant prognostic value in different tumors. The primary aim is to analyze the role of TILs and RNL as a predictive factor, in patients with MIBC and objective response rate (ORR). The secondary aim is to evaluate the relationship beteween BMI, tabaquism and ORR, in the same group of pts. Methods: A total of 35 pts with MIBC was included. All pts received neoadjuvant treatment, with cisplatin and gemcitabine. Also, TILs was determined as the percentage of mononuclear inflammatory cells in the total stromal area counted in 5 high-power fields (CGA, X 400), on the invasive front of the tumor. The NLR was obtained before treatment and value of cut-off was 2.6. the evaluation of ORR was calculated used the T-Test and Chi Square test. Results: Of the total of 35 patients. 15 patients obtained complete response (CR), 6 pts partial response (PR), 5 pts stable disease (SD) and 9 pts disease progression (DP). In 21 tumor sample was observed an intense TILS. These patients obtained a better ORR 42.6 % vs 21.7% with low TILs in his tumor samples. The difference was statistically significant (p: 0.001). Regarding NLR, only 9 pts presented response with NLR > 2,6 vs 12 pts with response and RNL < 2.6. The difference was not statistically significant. When analyzing the smoking and response. We could observe response of 69.6% in smoking pts vs Non- smoking the response was 41.7%. Regarding BMI, 21 pts with response of 27% and 14 patient without response 25.9%. But the differences were not significant in any groups. Conclusions: We conclude that the presence of TILS in tumor samples, in patients with MIBC, could be a predictive factor against the response to neoadjuvant treatment. With the other variables, smoking and BMI, we did not observed influence in ORR. We will keep working to obtain a greater number of patients. Then we could have a better analysis and statistical power.

A phase I/II study of TQ-B2450, a PD-L1 mAb, plus anlotinib in EGFR+ advanced NSCLC patients failed to prior EGFR TKI therapies.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21062-e21062
Author(s):  
Meiqi Shi ◽  
Li Wang ◽  
Shaorong Yu ◽  
Fei Yan ◽  
Wei Peng ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Overall Survival ◽  
Phase I ◽  
Phase Ii ◽  
Advanced Nsclc ◽  
Phase 1 ◽  
Objective Response ◽  
Platinum Based Chemotherapy ◽  
Egfr Tki ◽  
Clinical Trial Information

e21062 Background: Platinum-based chemotherapy is the standard therapy for the patients(pts) with EGFR-mutation–positive advanced NSCLC failed to prior EGFR TKI therapies. However, the IMpower150 study subgroup analyses showed Atezolizumab (PD-L1) plus bevacizumab and chemotherapy improved overall survival in EGFR TKI treated NSCLC. This ongoing phase I/II study designed to assess the benefit of the chemo-free combination of TQ-B2450, a humanized PD-L1 mAb, plus anlotinib in EGFR+ advanced NSCLC pts failed to prior EGFR TKI therapies. Methods: Pts with EGFR+ advanced NSCLC who failed to prior EGFR TKI therapies were eligible. Pts with previous received platinum-based chemotherapy were excluded. Anlotinib was given orally at dose of 8mg to 12mg for 2 weeks of a 21-day cycle (days 1-14), with TQ-B2450 given at 1200mg every 3 weeks on day 1. Phase I determined RP2D. In the phase II part, pts were assessed for efficacy and tolerability. The primary endpoint for the phase II part is the progression free survival (PFS). Secondary endpoints were objective response rate (ORR) disease control rate (DCR), overall survival (OS), and safety. Assuming an expected the median PFS of 9 months (5 months in chemotherapy), and a loss to follow-up of 10%, a total of 54 pts were required to have 90% power at a two-tailed alpha of 0.05 at the phase II part. Results: As of 12 Jan 2021, 22 pts were enrolled (9 in phase 1, 14 in phase 2). 18 pts were included in efficacy and safety analysis. The median age was 64.5 years with 61% male. 50% pts harbored EGFR exon19 deletion, 44% pts had exon21 L858R mutation. While 39% pts had T790M mutation who progressed after osimertinib treatment. The dose escalation cohort included 9 pts, no dose limiting toxicity occurred. 13 pts in the phase II part were administered with dose of 12 mg for anolitinib and 1200mg for TQ-B2450. Of the evaluable pts(n = 18), ORR was 11.1%, DCR was 77.8%, median PFS was 8.0 months (95% CI 4.9 to 11.1). Most frequent TRAE included hypertension (27.8%), hand and foot skin reaction (22.2%) and proteinuria (16.7%). Grade 3 TRAE occurred in 16.7% pts(3/18 pts), all were hypertension, and no Grade 4/5 TRAE were observed. Dose delay due to TRAE occurred in 22.2% patients while no one discontinued treatment due to TRAE. Conclusions: The chemo-free combination of TQ-B2450, a PD-L1 mAb, plus anlotinib has shown a promising anti-tumor efficacy with a more favorable safety profile for pts with EGFR+ advanced NSCLC who failed to prior EGFR TKI therapies. Pts will be continuously monitored for safety and efficacy readouts (PFS, DOR and OS). Clinical trial information: ChiCTR1900026273. Clinical trial information: ChiCTR1900026273.

Phase II study of amrubicin (AMR) in patients (pts) with non-small cell lung cancer (NSCLC) previously treated with platinum-based chemotherapy: WJTOG0401

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8059-8059
Author(s):  
H. Hayashi ◽  
H. Kaneda ◽  
I. Okamoto ◽  
M. Miyazaki ◽  
S. Kudoh ◽  
...  
Keyword(s):  
Stable Disease ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Objective Response ◽  
Activity Level ◽  
Clinical Activity ◽  
Significant Activity ◽  
Platinum Based Chemotherapy ◽  
Previously Treated ◽  
Grade 3

8059 Background: AMR is a totally synthetic 9-aminoanthracycline and a novel topoisomerase II inhibitor. AMR has shown promising clinical activity for advanced NSCLC as well as SCLC. This trial was conducted to evaluate the efficacy and safety of AMR for pts with NSCLC previously treated with platinum-based chemotherapy. Methods: Eligible pts had a performance status 0 to 1, previous treatment with one platinum-based chemotherapy for advanced NSCLC, and adequate organ function. Pts received AMR 40 mg/m2 intravenously on days 1–3 every 3 weeks. The primary endpoint was the objective response rate, which determined the sample size based on an optimal two-stage design. With the target activity level of 18% and the lowest response rate of interest set at 5%, 60 eligible patients were required with a 90% power to accept the hypothesis and a 5% significance level to reject the hypothesis. Results: Sixty-one pts (median age, 63 years; range 51–74 years) were enrolled. The median treatment cycles were 2 (range, 1–15). No complete responses and 7 partial responses were observed, giving an overall response rate of 11.5% (95% CI, 4.7–22.2%). Twenty patients (32.8%) had stable disease and 34 patients (55.7%) had progressive disease as the best response. The overall disease control rate (complete response + partial response + stable disease) was thus 44.3% (95% CI, 31.5–57.6%). The median overall survival and 1-year survival rate were 8.5 months and 32.0%, respectively. Grade 3/4 hematological toxicities were neutropenia (82%), anemia (27.9%) and thrombocytopenia (24.6%). Grade 3/4 non-hematological toxicities were anorexia (9.8%), febrile neutropenia (29.5%) and pneumonitis (1.6%). No treatment-related death and cardiac toxicity were observed. Conclusions: AMR exhibits significant activity with manageable toxicities as second-line therapy for advanced NSCLC. [Table: see text]

scholarly journals Predicting the Role of DNA Polymerase β Alone or with KRAS Mutations in Advanced NSCLC Patients Receiving Platinum-Based Chemotherapy

2020 ◽  
Vol 9 (8) ◽  
pp. 2438
Author(s):  
Maria Francesca Alvisi ◽  
Monica Ganzinelli ◽  
Helena Linardou ◽  
Elisa Caiola ◽  
Giuseppe Lo Russo ◽  
...  
Keyword(s):  
Dna Polymerase ◽  
Advanced Nsclc ◽  
Objective Response ◽  
Progression Free Survival ◽  
Dna Polymerase Β ◽  
Kras Mutations ◽  
Platinum Based Chemotherapy ◽  
Negative Role ◽  
Poor Outcomes ◽  
Nsclc Patients

Clinical data suggest that only a subgroup of non-small cell lung cancer (NSCLC) patients has long-term benefits after front-line platinum-based therapy. We prospectively investigate whether KRAS status and DNA polymerase β expression could help identify patients responding to platinum compounds. Prospectively enrolled, advanced NSCLC patients treated with a first-line regimen containing platinum were genotyped for KRAS and centrally evaluated for DNA polymerase β expression. Overall survival (OS), progression-free survival (PFS), and the objective response rate (ORR) were recorded. Patients with KRAS mutations had worse OS (hazard ratio (HR): 1.37, 95% confidence interval (95% CI): 0.70–2.27). Negative DNA polymerase β staining identified a subgroup with worse OS than patients expressing the protein (HR: 1.43, 95% CI: 0.57–3.57). The addition of KRAS to the analyses further worsened the prognosis of patients with negative DNA polymerase β staining (HR: 1.67, 95% CI: 0.52–5.56). DNA polymerase β did not influence PFS and ORR. KRAS may have a negative role in platinum-based therapy responses in NSCLC, but its impact is limited. DNA polymerase β, when not expressed, might indicate a group of patients with poor outcomes. KRAS mutations in tumors not expressing DNA polymerase β further worsens survival. Therefore, these two biomarkers together might well identify patients for whom alternatives to platinum-based chemotherapy should be used.

EFFECTIVENESS OF ENDOBRONCHIAL PHOTODYNAMIC THERAPY IN COMBINATION WITH CHEMOTHERAPY IN NON-SMALL CELL LUNG CANCER

2017 ◽  
Vol 63 (6) ◽  
pp. 882-885
Author(s):  
Andrey Akopov ◽  
Anatoliy Rusanov ◽  
Margarita Urtenova ◽  
Nikita Kazakov ◽  
A. Cheremnykh ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Photodynamic Therapy ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Combined Treatment ◽  
Small Cell ◽  
Small Cell Lung ◽  
Results Of Treatment ◽  
Number Of Patients

Aim. To evaluate safety and effectiveness of combined treatment of non-small cell lung cancer (NSCLC) including chemotherapy and endobronchial PDT. Methods. Results of treatment for two groups of patients with central advanced NSCLC were compared, 75 patients in each. In arm A first line chemotherapy with endobronchial photodynamic therapy (PDT) was done, in arm B - chemotherapy only. PDT was performed with the use of chlorine based photosensitizers in the dose of 1 mg/kg body weight. Results. Investigated groups were comparable. No serious PDT complications were observed. The number of patients progression (p=0,05) was significantly different in favour of arm A. Remission in arm A was noted in 90% of patients, in arm B - in 76% (p=0,02). One-year survival was 60% and 41% for groups A and B, respectively (р=0,03). Conclusion. Combination of endobronchial PDT and chemotherapy is safe and effective, makes possible to improve results of treatment and survival in central advanced NSCLC.

Diagnostic and prognostic significance of circulating endothelial cell in advanced non-small cell lung cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18116-e18116
Author(s):  
Dongmei Yuan ◽  
Yanling Lv ◽  
Xingqun Ma ◽  
Hongbing Liu ◽  
Yi Shi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Objective Response ◽  
Prognostic Significance ◽  
Small Cell ◽  
Small Cell Lung ◽  
Platinum Based Chemotherapy ◽  
Nsclc Patients

e18116 Background: The aim of this study was to evaluate the diagnostic and prognostic value of circulating endothelial cells (CECs) during first-line therapy in patients with advanced non-small cell lung cancer (NSCLC). Methods: 102 newly diagnosed advanced NSCLC patients were enrolled in this study. The amount of CECs (CD45- CD31+ CD146+) was enumerated by flow cytometry at baseline and after two cycles of treatment. We correlated CEC counts and the reduction of CECs with objective response rate (ORR) and progression-free survival (PFS). Results: The CECs level was significantly higher in advanced NSCLC patients, ranging from 57 to 1300 cells/105 cells (n=102, mean±SD=299±221 cells/105 cells), than patients with benign lesions (n=35, 205±97 cells/105 cells), and healthy volunteers (n=34, 117±33 cells/105 cells). When the cut off value of CEC counts was 210 cells/105 cells, there was no significant association between CEC counts and OR/PFS of the enrolled patients. However, patients with CECs response after chemotherapy has more chances to achieve OR (P<0.001), and such patients showed longer PFS than those without CECs response (P = 0.041). In the multivariate analysis, the independent prognostic roles of performance status (HR: 3.245, 95% CI: 1.189-8.854), brain metastasis (HR: 3.673, 95% CI: 1.062-12.704), and CECs response (HR: 0.046, 95% CI: 0.188-0.984) were found. Conclusions: The CEC counts could be considered as the diagnostic biomarker for advanced NSCLC patients. And the reduction of CECs after treatment might be more ideal than the CEC counts as a predictive or prognostic factor in patients treated with platinum-based chemotherapy.

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