The depth of response was associated with the progression-free survival in advanced non-small cell lung cancer patients treated with EGFR-TKI.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20509-e20509
Author(s):  
Yutao Liu ◽  
Kai Zhang ◽  
Chengcheng Li ◽  
Xingsheng Hu ◽  
Jun Jiang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival ◽  
Depth Of Response ◽  
Egfr Tki

e20509 Background: Response Evaluation Criteria in Solid Tumors (RECIST) has been widely utilized to evaluate the new therapeutic strategies in cancer, however, RECIST fails to differentiate the heterogeneity of response in highly active therapies. Depth of response (DepOR), defined as maximum percent change in tumor size compared with baseline, may provide a new strategy to evaluate disease response. In the present study, we studied the association between DepOR and progression-free survival (PFS) in patients with advanced non-small cell lung cancer (NSCLC) treated with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). Methods: Advanced NSCLC patients harboring EGFR driver mutation (L858R or 19del) treated with EGFR-TKI from August 2014 to July 2017 in two sites were retrospetively collected for analysis. Patients were divided into four groups by maximal tumor shrinkage (Q1 = 1-25%, Q2 = 26-50%, Q3 = 51-75%, Q4 = 76-100%). Kaplan-Meier curves were plotted for PFS by DepOR and the hazard ratio (HR) was determined through univariable and multivariable Cox regression models. Results: In total, 265 patients were included for analysis. The number for Group Q1-Q4 was 91, 73, 65 and 36, respectively. The greater DepOR was significantly associated with a longer PFS (Log-rank P for trend < 0.0001). The DepOR vs PFS analyses HR were 0.58 (0.42-0.80) for Q2, 0.49 (0.35-0.69) for Q3 and 0.33 (0.22-0.50) for Q4 compared with Q1. In the multivariable cox regression model, abnormal LDH, brain metastasis and male were also found to be associated with poorer PFS (P < 0.05). Conclusions: Greater DepOR was significantly associated with a longer PFS in advanced NSCLC treated with EGFR-TKI, suggesting that it may be a useful clinical outcome to more efficiently evaluate the response of targeted therapy.

scholarly journals Depth of Response was Associated with Progression-Free Survival in Patients with Advanced Non-small Cell Lung Cancer treated with EGFR-TKI

2019 ◽  
Vol 10 (21) ◽  
pp. 5108-5113
Author(s):  
Yu-Tao Liu ◽  
Kai Zhang ◽  
Cheng-Cheng Li ◽  
Xing-Sheng Hu ◽  
Jun Jiang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival ◽  
Depth Of Response ◽  
Egfr Tki

scholarly journals A Large Real-World Study on the Effectiveness of the Combined Inhibition of EGFR and MET in EGFR-Mutant Non-Small-Cell Lung Cancer After Development of EGFR-TKI Resistance

2021 ◽  
Vol 11 ◽  
Author(s):  
Li Liu ◽  
Jingjing Qu ◽  
Jianfu Heng ◽  
Chunhua Zhou ◽  
Yi Xiong ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Real World ◽  
Acquired Resistance ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival ◽  
Tki Resistance ◽  
Egfr Tki

BackgroundMET proto-oncogene amplification (amp) is an important mechanism underlying acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, the optimal treatment strategy after acquiring MET-amp-mediated EGFR-TKI resistance remains controversial. Our study compared three treatment strategies for patients with EGFR-mutant non-small-cell lung cancer (NSCLC) who were detected with MET-amp at EGFR-TKI progression using next-generation sequencing.MethodsOf the 70 patients included in the study, 38 received EGFR-TKI + crizotinib, 10 received crizotinib monotherapy, and 22 received chemotherapy. Clinical outcomes and molecular profiles were analyzed.ResultsThe objective response rate was 48.6% for EGFR-TKI + crizotinib group, 40.0% for crizotinib monotherapy group, and 18.2% for chemotherapy group. Patients who received EGFR-TKI + crizotinib had significantly longer progression-free survival than those who received crizotinib or chemotherapy (5.0 vs. 2.3 vs. 2.9 months, p = 0.010), but overall survival was comparable (10.0 vs. 4.1 vs. 8.5 months, p = 0.088). TP53 mutation (58.5%) and EGFR-amp (42.9%) were frequent concurrent mutations of the cohort. Progression-free survival was significantly longer for patients with either concurrent TP53 mutation (n = 17) (6.0 vs. 2.3 vs. 2.9 months, p = 0.009) or EGFR-amp (n = 13) (5.0 vs. 1.2 vs. 2.4 months, p = 0.016) in the EGFR-TKI + crizotinib group than the other two regimen. Potential acquired resistance mechanisms to EGFR-TKI + crizotinib included EGFR-T790M (n = 2), EGFR-L718Q (n = 1), EGFR-S645C (n = 1), MET-D1228H (n = 1), BRAF-V600E (n = 1), NRAS-Q61H (n = 1), KRAS-amp (n = 1), ERBB2-amp (n = 1), CDK4-amp (n = 1), and MYC-amp (n = 1).ConclusionOur study provides real-world clinical evidence from a large cohort that simultaneous inhibition of EGFR and MET could be a more effective therapeutic strategy for patients with MET-amp acquired from EGFR-TKI therapy.

scholarly journals Associations of cytosine deaminase gene polymorphisms with effectiveness of gemcitabine/cisplatin chemotherapy in patients of Xinjiang Uyghur and Han nationality with non-small cell lung cancer

2019 ◽  
Vol 34 (4) ◽  
pp. 389-397
Author(s):  
Jing Li ◽  
Dan Xu ◽  
Jian Huang ◽  
Yan-Na Wang ◽  
Xiao-Ping Ma ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Cox Regression ◽  
Cytidine Deaminase ◽  
Direct Sequencing ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival

Background: Cytidine deaminase (CDA) polymorphisms may affect the response to gemcitabine/cisplatin chemotherapy in patients with non-small cell lung cancer (NSCLC). This study is designed to investigate the associations of CDA-79A>C and 208G>A polymorphisms and gemcitabine/cisplatin chemotherapy effectiveness in Xinjiang Uyghur and Han patients. Methods: This prospective cohort study enrolled consecutive patients with stage IIIb/IV NSCLC administered gemcitabine/cisplatin chemotherapy at the First Affiliated Hospital, Medical College of Shihezi University and the First People’s Hospital, Kashgar Region. CDA-A79C and CDA-G208A polymorphisms were detected by direct sequencing. Progression-free survival was analyzed by the Kaplan-Meier method. Associations of A79C and G208A polymorphisms with treatment effectiveness and progression-free survival were analyzed using logistic regression and multivariate Cox regression analyses. Subgroup analyses based on ethnicity were performed. Results: The study enrolled 120 patients. A79C and G208A polymorphisms followed the Hardy-Weinberg equilibrium. The frequencies of the AA, AC, and CC genotypes and the A and C alleles of A79C were 52.2%, 29.9%, 17.9%, 67.2%, and 32.8%, respectively, in Han patients and 75.4%, 18.9%, 5.7%, 84.9%, and 5.1%, respectively, in Uyghur patients. Uyghur patients had lower frequencies of A79C-AC/CC genotypes, A79C-C allele, G208A-GA genotype, and G208A-A allele ( P<0.05). Compared with A79C-AA, the odds of ineffective chemotherapy were increased for A79C-AC (odds ratio [OR] 2.818; 95% confidence interval [95% CI] 1.031, 7.705; P=0.043) and A79C-CC (OR 9.864; 95% CI 1.232, 78.966; P=0.031). G208A polymorphisms did not influence chemotherapy effectiveness. Chemotherapy was more effective in Han patients than in Uyghur patients for A79C-AC and G208A-GG. Progression-free survival was longer for A79C-AA versus A79C-AC/CC (10 vs. 7 months, P=0.004) and G208A-GA/AA vs. G208A-AA (12 vs. 8 months, P=0.010). Polymorphisms of A79C (hazard ratio [HR] 1.617; 95% CI 1.009, 2.592; P=0.046) and G208A (HR 2.193; 95% CI 1.055, 4.557; P=0.035) were associated with progression-free survival. Conclusion: For Uyghur and Han ethnic groups, A79C and G208A polymorphisms can be used as a promising biomarker for the chemotherapy efficacy and prognosis of NSCLC.

scholarly journals Serum Metabolite Biomarkers Predictive of Response to PD-1 Blockade Therapy in Non-Small Cell Lung Cancer

2021 ◽  
Vol 8 ◽  
Author(s):  
Xiaoqun Nie ◽  
Liliang Xia ◽  
Fang Gao ◽  
Lixia Liu ◽  
Yi Yang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Validation Cohort ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Discovery Cohort ◽  
Free Survival ◽  
Metabolomic Profiling

Background: Despite remarkable success of immunotherapies with checkpoint blockade antibodies targeting programmed cell death protein 1 (PD-1), the majority of patients with non-small-cell lung cancer (NSCLC) have yet to receive durable benefits. We used the metabolomic profiling of early on-treatment serum to explore predictors of clinical outcomes of anti-PD-1 treatment in patients with advanced NSCLC.Methods: We recruited 74 Chinese patients who had stage IIIB/IV NSCLC-proven tumor progression and were treated with PD-1 inhibitor. The study was comprised of a discovery cohort of patients treated with nivolumab and two validation cohorts of patients receiving tislelizumab or nivolumab. Serum samples were collected 2–3 weeks after the first infusion of PD-1 inhibitor. Metabolomic profiling of serum was performed using ultrahigh performance lipid chromatograph-mass spectrometry. The serum metabolite biomarkers were identified using an integral workflow of nontargeted metabolomic data analysis.Results: A serum metabolite panel consisting of hypoxanthine and histidine was identified and validated as a predictor of response to PD-1 blockade treatment in patients with advanced NSCLC. High levels of both hypoxanthine and histidine in early on-treatment serum were associated with improved progression-free survival [hazard ratio (HR) = 0.078, 95% confidence interval (CI), 0.027–0.221, p &lt; 0.001] and overall survival (HR = 0.124, 95% CI, 0.039–0.397, p &lt; 0.001) in the discovery cohort. The serum metabolite panel showed a high sensitivity and specificity in distinguishing responders and non-responders in the validation cohorts 1 and 2, with an area under the receiver-operating characteristic curve of 0.933 and 1.000, respectively. High levels of serum hypoxanthine and histidine were correlated with improved progression-free survival in the validation cohort 1 (HR = 0.137, 95% CI, 0.040–0.467, p = 0.001) and in the validation cohort 2 (HR = 0.084, 95% CI, 0.009–0.762, p = 0.028).Conclusion: Our results revealed that hypoxanthine and histidine in early on-treatment serum are predictive biomarkers of response to PD-1 blockade therapy in patients with advanced NSCLC. The serum biomarker panel would enable early identification of NSCLC patients who may benefit from PD-1 blockade therapy.

Neutrophil to lymphocyte ratio as predictive of prolonged progression free survival (PFS) and overall survival (OS) in patients with metastatic non-small cell lung cancer (NSCLC) treated with second-line PD-1 immune checkpoint inhibitors.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e14530-e14530 ◽  
Author(s):  
Stephanie Labomascus ◽  
Ibtihaj Fughhi ◽  
Philip Bonomi ◽  
Mary J. Fidler ◽  
Jeffrey Allen Borgia ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Tumor Microenvironment ◽  
Small Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Progression Free Survival ◽  
Small Cell ◽  
Second Line ◽  
Small Cell Lung ◽  
Free Survival

e14530 Background: Baselinehigh neutrophil to lymphocyte ratio (NLR) has been associated with inferior overall survival in patients with stage III/IV NSCLC. Inflammation and neutrophilic infiltrates in the tumor microenvironment appear to inhibit anti-tumor immune response. We suspect that NLR might reflect the level of inflammation in tumor microenvironment. The objectives of this study were to evaluate potential relationships between pretreatment NLR and and PFS and OS in advanced NSCLC patients treated with second-line nivolumab or pembrolizumab. Methods: Patients with stage IV NSCLC who received at least one cycle of nivolumab or pembrolizumab after first-line treatment with a platinum doublet between January 2015 and December 2016 were included. Patient demographics including NLR at baseline, date of starting immunotherapy, and date of progression were recorded. The association between NLR and duration of response was assessed using a Mann-Whitney-Wilcoxon test. A cutoff of NLR of 3.5 and 5.0 based on published data (ref) were analyzed for differences in median overall survival and progression free survival. Results: 113 patients were analyzed: median age 68, male/female 38.9%/61.1%, 15% never smoked. The median PFS for patients with NLR < 5 was 4.14 months vs. 2.27 months in those with NLR > 5 (p = 0.031). Overall survival was also impacted by NLR. There were a total of 29 deaths in the cohort, 24 of these occurred in patients with NLR > 3.5 and 5 were in patients with NLR < 3.5. A lower NLR at baseline was significantly associated with improved overall survival (p = 0.036). Conclusions: A low baseline NLR is associated with superior progression free survival and overall survival in metastatic non-small cell lung cancer patients treated with nivolumab or pembrolizumab. These findings suggest that evaluating mediators of inflammation might help to identify potential therapeutic targets which could enhance effectiveness of PD-1 immune check point inhibitors in advanced NSCLC.

Hypofractionated Radiotherapy for Locally or Systemically Advanced Non-small Cell Lung Cancer

2021 ◽  
Author(s):  
Jiajia Zhang ◽  
Zi'ning Qi ◽  
Dong Han ◽  
Siying Chen ◽  
Jifeng Sun ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Progression Free Survival ◽  
Small Cell ◽  
Hypofractionated Radiotherapy ◽  
Small Cell Lung ◽  
Free Survival ◽  
Local Progression

Abstract Background: Palliative thoracic radiotherapy (RT) can improve local control and survival in patients with unresectable locally or systemically advanced non-small cell lung cancer (NSCLC), but the optimal RT dose has not been well-defined. We investigated the survival outcomes of patients with NSCLC who underwent hypofractionated radiotherapy (HFRT).Methods: We retrospectively investigated survival and adverse effects among 74 patients with locally or systemically advanced NSCLC who received HFRT (45 Gy/15 fractions) at our institution.Results: The median overall survival (OS) was 18.7 months, with 1- and 2-year OS rates of 65.9% and 33.9%, respectively. The median local progression-free survival (LPFS) was 7.2 months, with 1- and 2-year LPFS rates of 27.9% and 9.4%, respectively. Sixteen patients (21.6%) developed grade ≤2 pneumonitis and 14 (19%) developed grade ≤2 esophagitis; no grades ≥3 pneumonitis or esophagitis occurred.Conclusions: HFRT is safe, tolerable, and effective for patients with unresectable locally or systemically advanced NSCLC exhibiting poor prognostic factors.

scholarly journals Perbandingan Rejimen Kemoterapi Cisplatin Etoposide dengan Cisplatin-Docetaxel dalam Hal Kesintasan 2 Tahun dan Progression-Free Survival Pasien Kanker Paru Stadium Lanjut Jenis Non-Small Cell

2017 ◽  
Vol 3 (2) ◽  
pp. 67
Author(s):  
Salman Paris Harahap ◽  
Noorwati Sutandyo ◽  
Cleopas Martin Rumende ◽  
Hamzah Shatri
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Median Time ◽  
Cell Lung Cancer ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival ◽  
Cox Regression Analysis

Pendahuluan. Salah satu terapi dari kanker paru jenis Non-Small Cell Lung Cancer (NSCLC) stadium lanjut adalah kemoterapi. Jenis kemoterapi yang sering digunakan di Indonesia adalah cisplatin- toposide dan cisplatin-docexatel. Tolak ukur keberhasilan pengobatan adalah kesintasan dan Progression Free Survival (PFS). Keberhasilan kemoterapi dipengaruhi oleh banyak faktor, seperti resistensi terhadap sitostatika, dosis, intensitas pemberian, jenis kemoterapi, jenis histologi, stadium, perfoma status, komorbiditas dan sosial ekonomi. Di Indonesia, pendanaan dan jenis rejimen kemoterapi masih merupakan masalah terhadap keberhasilan terapi.Metode. Penelitian menggunakan desain kohort retrospektif dengan analisis kesintasan. Pasien yang dimasukkan dalam penelitian ini adalah pasien kanker paru jenis NSC stadium lanjut (minimal stadium IIIa), yang datang ke Rumah Sakit Kanker Dharmais (RSKD) dan Rumah Sakit dr. Cipto Mangunkusumo (RSCM) Jakarta pada Januari 2006–Desember 2010 yang baru pertama kali dikemoterapi sampai selesai, sebanyak 6 kali dan dilakukan pengamatan 2 tahun. Data dianalisis dengan program SPSS 16.0 dan dilakukan analisis cox regression yang ditampilkan dalam kurva Kaplan Meier.Hasil. Didapatkan sebanyak 55 pasien menggunakan cisplatin-etoposide (EC) dan 55 pasien menggunakan cisplatindocexatel (DC). Terdapat perbedaan kesintasan 1 tahun EC sebesar 30,9% dan DC sebesar 47,3% dengan nilai p= 0,030. Sementara itu, pada kesintasan 2 tahun, juga terdapat perbedaan EC sebesar 0% dan DC sebesar 5,5%, dengan nilai p= 0,003, demikian juga median time survival antara EC selama 27 minggu dengan DC selama 38 minggu (p <0,016). Dibandingkan DC, kemoterapi EC dapat meningkatkan risiko kematian dengan HR 1,684 (IK95% 1,010-2,810). Selain itu,terdapat perbedaan PFS 24 minggu antara kemoterapi EC (54,5%) dan DC (32,7%) dengan nilai p= 0,022.Simpulan. Kesintasan cisplatin-docexatel lebih baik bila dibandingkan dengan cisplatin-etoposide, demikian juga dengan progression free survival.Kata Kunci: cisplatin-docexatel, cisplatin-etoposide, kesintasan, NSCLC, PFS Comparison of Chemotherapy Regiments between Cisplatin Etoposide and Cisplatin-Docetaxel on 2-Year and Progression-Free Survival in Late-Stage Non-Small Cell Lung Cancer PatientsIntroduction. Chemotherapy is one of therapy choices for the advanced Non-Small Cell Lung Cancer (NSCLC). The success in therapy is measured with the 1-year survival, 2-year survival and the Progression Free Survival (PFS). The success is influenced by many factors: resistant to the citostatic, dosage, administer intensity, chemotherapy regiment, type histology, stage, performance status, comorbidity and social economic. In Indonesia, funding and chemotherapy regiment become the challenge for the success of therapy.Methods. The study used the Retrospective Cohort study with survival analysis. The Patients included in this study were the advanced NSC Lung Cancer (At least Stadium IIIa) who came to RSKD and RSCM during Jan 2006 – December 2010 for their first chemotherapy until finished the cycle (6 times) and had monitored for 2 years. Data was analyzed using cox regression analysis SPSS 16.0, and featured on the Kaplan Meier Curve. Results. Fifty five patients used EC and the other 55 patients used DC. There’s difference on survival where 1 year survival EC is 30,9% and DC is 47,3%, with p 0.030. Two year survival CE is 0% and for DC is 5.5%, with p 0.003. Also with the Median time survival between EC for 27 weeks and DC for 38 weeks with p < 0.016. Compared to DC, EC chemotherapy can increase the death risk by HR 1,684 (CI 95% 1,010-2,810), twenty four weeks PFS with EC is 54.5%, DC is 32.7% with p= 0.022. Conclusions. The survival with cisplatin-docexatel is better compared to cisplatin-etoposide, this applies to PFS as well. Keywords: cisplatin docetaxel, cisplatin etoposide, NSCLC, PFS, Survival

A randomized discontinuation phase II trial of ridaforolimus in non-small cell lung cancer (NSCLC) patients with KRAS mutations.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7531-7531 ◽  
Author(s):  
Gregory J. Riely ◽  
Julie R. Brahmer ◽  
David Planchard ◽  
Lucio Crinò ◽  
Robert Charles Doebele ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Stable Disease ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Kras Mutations ◽  
Free Survival

7531 Background: Mutations in KRAS are present in ~25% of patients with advanced NSCLC. Preclinical data support the role of mammalian target of rapamycin (mTOR) in KRAS mediated oncogenesis. Ridaforolimus is an inhibitor of mTOR which has been shown to have efficacy in advanced endometrial cancer and soft tissue sarcoma. Everolimus, another mTOR inhibitor was previously evaluated in unselected patients with advanced NSCLC and found to have a response rate <5%. We hypothesized that by enrichment for patients with NSCLC and KRAS mutations, treatment with ridaforolimus would be associated with prolonged stable disease relative to available standard treatments for NSCLC. Methods: Patients with stage IIIB/IV non-small cell lung cancer with KRAS mutation who had received prior chemotherapy for NSCLC began treatment with oral ridaforolimus 40 mg once daily on a 5 day/week schedule. After 8 weeks, patients with >30% tumor shrinkage remained on ridaforolimus and patients with >20% tumor growth discontinued treatment. Patients with stable disease were randomized 1:1 to placebo or ridaforolimus. The primary endpoint of the study was progression-free survival (PFS) after randomization. Results: 79 patients were enrolled (40 women, median age 58 [range 28-85]). The overall response rate (CR+PR) at 8 weeks was 1/79 (1%, 95% CI 0-7%).  28 patients with stable disease at 8 weeks were randomized to ridaforolimus or placebo.  Median PFS based on investigator assessment from randomization was significantly longer with ridaforolimus (4 months) than placebo (2 months, p=0.013, HR 0.36).  Median OS from randomization was 18 months in the ridaforolimus treated arm and 5 months in the placebo treated group, (HR 0.46, p=0.09).  The most common grade ≥3 adverse events were fatigue (10%), mucositis/stomatitis (10%), pneumonia (10%), dyspnea (9%), diarrhea (6%), and hyperglycemia (6%). Conclusions: In patients with KRAS mutant NSCLC who had stable disease after 8 weeks of ridaforolimus, ridaforolimus was associated with prolonged progression-free survival.  Further evaluation of ridaforolimus in this patient population is warranted. 

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