scholarly journals Impact of Genetic Polymorphisms on the Metabolic Pathway of Vitamin D and Survival in Non-Small Cell Lung Cancer

Nutrients ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 3783
Author(s):  
Laura Elena Pineda Lancheros ◽  
Cristina Pérez Ramírez ◽  
Almudena Sánchez Martín ◽  
José María Gálvez Navas ◽  
Fernando Martínez Martínez ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Vitamin D ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Metabolic Pathway ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Resected Nsclc

Vitamin D has been associated with risk, development, and progression of cancer. However, the genes involved in its metabolism are highly polymorphic, compromising its activity. The aim of this study is to evaluate the association between the gene polymorphisms involved in the metabolic pathway of vitamin D and survival in patients with non-small-cell lung cancer (NSCLC). The study was designed as an observational cohort which included 194 Caucasians patients from southern Spain with NSCLC. Real-time polymerase chain reaction was used to analyze the following polymorphisms: CYP27B1 rs4646536, rs3782130, and rs10877012; CYP24A1 rs6068816 and rs4809957; GC rs7041; CYP2R1 rs10741657; VDR rs1544410 (BsmI), rs11568820 (Cdx-2), rs2228570 (FokI), rs7975232 (ApaI), and rs731236 (TaqI). Progression-free survival (PFS) and overall survival were assessed. Cox regression showed that rs4646536 was associated with PFS in the general population (p = 0.0233) and in the non-resected NSCLC subgroup (p = 0.0233). In the resected NSCLC subgroup, rs11568820 was associated with OS (p = 0.0129) and rs7041 with PFS (p = 0.0447). In the non-resected NSCLC subgroup, rs6068816 was associated with PFS (p = 0.0048) and OS (p = 0.0089) and rs731236 and rs7975232 were associated with OS (p = 0.0005) and PFS (p = 0.0002), respectively. The other polymorphisms showed no effect on the results. The rs4646536, rs6068816, rs7041, rs11568820, rs731236, and rs7975232 polymorphisms are associated with survival in NSCLC and may have a substantial role as prognostic markers of the disease.

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.

C/EBPα expression by immunohistochemistry lacks prognostic or predictive significance in primary resected non-small cell lung cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7202-7202
Author(s):  
D. B. Costa ◽  
P. Stephenson ◽  
O. Kocher ◽  
D. G. Tenen ◽  
R. H. Feins ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Molecular Mechanisms ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Resected Nsclc ◽  
Thoracic Radiation

7202 Background: The transcription factor CCAAT/enhancer binding protein alpha (C/EBPα) is down-regulated in a majority of lung cancers. We sought to determine if C/EBPα could be a prognostic or predictive factor in non-small-cell lung cancer (NSCLC). Methods: Our cohort originated from ECOG 3590/4592 (randomized trial of postoperative adjuvant therapy with thoracic radiation or cisplatin and etoposide plus thoracic radiation in patients with completely resected stages II and IIIA NSCLC; and its laboratorial study). 166 tumor samples contained material for immunohistochemical (IHC) analysis of C/EBPα expression. We used a scoring system comparing tumor staining to that of basal bronchial cells (3+). 0 or 1+ (weak) staining suggested lack of, while 2 or 3+ (strong) suggested C/EBPα expression. Our primary outcomes were differences in progression-free and overall survival between the groups with weak or strong staining. Results: Among the 166 patients analyzed for C/EBPα IHC, the median progression free and overall survival were 30.7 and 40.3 months, respectively; which do not differ from the complete E4592 cohort. 92 patient samples (55%) had 0 or 1+ staining, and the remaining 74 (45%) 2 or 3+. The median progression free survival for patients with weak and strong C/EBPα IHC expression was 31.5 and 30.2 months, respectively (p = 0.84). The median overall survival between the weak and strong groups was 47.5 and 38.3 months, respectively (p = 0.54). 10 years after enrollment, 27% (25/92) of patients were alive in the weak, and 24% (18/74) in the strong C/EBPα IHC group. No difference between our primary outcomes by C/EBPα expression was identified. There was no difference in outcome by treatment arm, tumor histology, stage, or patient’s characteristics. There was a trend towards loss of C/EBPα and less differentiated tumor samples (p = 0.07). Conclusions: C/EBPα is a novel tumor suppressor gene in lung cancer with loss of expression in over 50% of NSCLC. However, our data demonstrate that in a subset of patients with resected NSCLC, C/EBPα IHC status is neither a prognostic nor a predictive marker. Further studies are needed to establish the molecular mechanisms of C/EBPα inactivation in lung cancer and its possible role as a new therapeutic target. No significant financial relationships to disclose.

scholarly journals Avoiding Absolute Quantification Trap: A Novel Predictive Signature of Clinical Benefit to Anti-PD-1 Immunotherapy in Non-Small Cell Lung Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Chengming Liu ◽  
Sihui Wang ◽  
Sufei Zheng ◽  
Fei Xu ◽  
Zheng Cao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Practice ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Cox Regression ◽  
Unmet Need ◽  
Progression Free Survival ◽  
Absolute Quantification ◽  
Small Cell ◽  
Small Cell Lung

Immunotherapy has been focused on by many oncologists and researchers. While, due to technical biases of absolute quantification, few traditional biomarkers for anti-PD-1 immunotherapy have been applied in regular clinical practice of non-small cell lung cancer (NSCLC). Therefore, there is an urgent and unmet need for a feasible tool—immune to data source bias—for identifying patients who might benefit from ICIs in clinical practice. Using the strategy based on the relative ranking of gene expression levels, we herein proposed the novel BRGP index (BRGPI): four BRGPs significantly related with progression-free survival of NSCLC patients treated with anti-PD-1 immunotherapy in the multicohort analysis. Moreover, stratification and multivariate Cox regression analyses demonstrated that BRGPI was an independent prognostic factor. Notably, compared to PD-L1, BRGPI exerted the best predictive ability. Further analysis showed that the patients in the BRGPI-low and PD-L1-high subgroup derived more clinical benefits from anti-PD-1 immunotherapy. In conclusion, the prospect of applying the BRGPI to real clinical practice is promising owing to its powerful and reliable predictive value.

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

Overexpression of VEGF-C and -D may predict unfavorable outcome in resected non-small cell lung cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21114-21114
Author(s):  
Y. Ko ◽  
C. Jung ◽  
M. Lee ◽  
J. Kang ◽  
Y. Hong ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Prognostic Factors ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Cox Regression ◽  
Small Cell ◽  
Tissue Array ◽  
Vegf Receptor ◽  
Small Cell Lung ◽  
Resected Nsclc

21114 Background: Correlation of Vascular endothelial growth factor (VEGF)-C, VEGF-D and/or VEGF receptor 3 (VEGFR-3) with lymphatic spread, tissue invasion and poor clinical outcomes has been observed in various cancers. Nodal metastasis is known to one of poor prognostic factors in non-small cell lung cancer (NSCLC). We investigated the correlation of VEGF-C,-VEGF-D and VEGFR-3 with clinicopathologic parameters and patient survival in NSCLC. Methods: Using immunohistochemial staining, we analyzed the protein expressions of VEGF-C, VEGFD and VEGFR-3 on the tissue array specimens from 180 patients with completely resected NSCLC. A 0 to +1 immunohistochemical staining (IHCS) of the cancer cell was defined as negative, +2 to +3 IHCS was as positive. Results: The expressions of VEGF-C, VEGF-D and VEGFR-3 were observed in 28.9%, 32.8% and 30.6% of cases, respectively. In the Cox regression-based multivariate analysis, it was proved that VEGF-C and D proved to be an independent prognostic factors as well as known prognostic factors, such as tumor size and lymph node metastases (VEGF-C, p=0.001; VEGF-D, p=0.014). VEGF-C expression showed statistically significant correlation with the expression of VEGFR-3 (p=0.02). Conclusion: To be taken, the present study revealed that VEGF-C and D expression may predict poor prognosis in resected NSCLC patients. Therefore, these results seems to be worth developing promising targeting inhibitors on lymphangiogenesis which plays major role in locoregional recurrence for surgically NSCLC patinets. No significant financial relationships to disclose.

scholarly journals Selpercatinib in RET fusion-positive non-small-cell lung cancer (SIREN): a retrospective analysis of patients treated through an access program

2021 ◽  
Vol 13 ◽  
pp. 175883592110196
Author(s):  
Oliver Illini ◽  
Maximilian Johannes Hochmair ◽  
Hannah Fabikan ◽  
Christoph Weinlinger ◽  
Amanda Tufman ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Real World ◽  
Objective Response ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Real World Setting ◽  
Access Program

Introduction: Rearranged during transfection (RET) gene fusions are rare genetic drivers in non-small cell lung cancer (NSCLC). Selective RET-inhibitors such as selpercatinib have shown therapeutic activity in early clinical trials; however, their efficacy in the real-world setting is unknown. Methods: A retrospective efficacy and safety analysis was performed on data from RET fusion-positive NSCLC patients who participated in a selpercatinib access program (named patient protocol) between August 2019 and January 2021. Results: Data from 50 patients with RET fusion-positive advanced NSCLC treated with selpercatinib at 27 centers in 12 countries was analyzed. Most patients were Non-Asian (90%), female (60%), never-smokers (74%), with a median age of 65 years (range, 38–89). 32% of the patients had known brain metastasis at the time of selpercatinib treatment. Overall, 13 patients were treatment-naïve, while 37 were pretreated with a median of three lines of therapy (range, 1–8). The objective response rate (ORR) was 68% [95% confidence interval (CI), 53–81] in the overall population. The disease control rate was 92%. The median progression-free survival was 15.6 months (95% CI, 8.8–22.4) after a median follow-up of 9 months. In patients with measurable brain metastases ( n = 8) intracranial ORR reached 100%. In total, 88% of patients experienced treatment-related adverse events (TRAEs), a large majority of them being grade 1 or 2. The most common grade ⩾ 3 TRAEs were increased liver enzyme levels (in 10% of patients), prolonged QTc time (4%), abdominal pain (4%), hypertension (4%), and fatigue/asthenia (4%). None of patients discontinued selpercatinib treatment for safety reasons. No new safety concerns were observed, nor where there any treatment-related death. Conclusions: In this real-world setting, the selective RET-inhibitor selpercatinib demonstrated durable systemic and intracranial antitumor activity in RET fusion-positive NSCLC and was well tolerated.

scholarly journals SURG-05. IDEAL TREATMENT REGIMEN FOR PATIENTS WITH ≥1 BRAIN METASTASIS FROM PRIMARY NON-SMALL-CELL LUNG CANCER – A SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii204-ii204
Author(s):  
Karanbir Brar ◽  
Yosef Ellenbogen ◽  
Behnam Sadeghirad ◽  
Jiawen Deng ◽  
Winston Hou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Targeted Therapies ◽  
Meta Analysis ◽  
Performance Status ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
China National Knowledge Infrastructure

Abstract BACKGROUND Brain metastases (BM) are common in non-small cell lung cancer (NSCLC). The aim of this study was to assess the comparative effectiveness of treatments for BM from NSCLC. METHODS We searched MEDLINE, EMBASE, Web of Science, ClinicalTrials.gov, CENTRAL and references of key studies for randomized controlled trials (RCTs) published until October 2018. We also searched the Chinese databases Wanfang Data, Wanfang Med Online, China National Knowledge Infrastructure, and Chongqing VIP Information for RCTs published until September 2019. Trials including &gt; 10 patients were selected. The primary outcomes were overall survival (OS) and intracranial progression-free survival (PFS). We used a frequentist random-effects model for network meta-analysis and assessed the certainty of evidence using the GRADE approach. RESULTS Among 8798 abstracts, 106 RCTs (9452 patients) met inclusion criteria. Median sample size was 67 (range 25-554). All trials included adult patients with histologically proven NSCLC and &gt;1 BM proven on CT/MRI. Of trials that reported performance status (e.g. ECOG or KPS, n=67), 63/67 excluded patients with non-favorable performance status. Interventions assessed included surgery, WBRT, SRS, targeted therapies (i.e. EGFR/ALK inhibitors), and chemotherapy. Compared to WBRT alone, several interventions demonstrated a statistically significant increase in median OS, including non-targeted chemotherapy + surgery (MD: 415.3 days, 95% CI: 31.3-799.4), WBRT + EGFRi (MD: 200.2 days, 95% CI:146.3-254.1), and EGFRi alone (MD: 169.7 days, 95% CI: 49.7-289.7). Among all interventions, only WBRT + EGFRi showed a significant improvement in median PFS (MD: 108.0 days, 95%CI: 48.5-167.5). CONCLUSIONS Our preliminary analyses indicate an OS and PFS benefit on the addition of EGFR inhibitors to WBRT for the treatment of BMs from NSCLC. Further analyses of hazard ratios for OS/PFS are underway, and subgroup analyses are planned. These data support the growing role of targeted therapies in the treatment of BMs, particularly in susceptible mutant tumours.

scholarly journals The Gustave Roussy Immune (GRIm)-Score Variation Is an Early-on-Treatment Biomarker of Outcome in Advanced Non-Small Cell Lung Cancer (NSCLC) Patients Treated with First-Line Pembrolizumab

2021 ◽  
Vol 10 (5) ◽  
pp. 1005
Author(s):  
Edoardo Lenci ◽  
Luca Cantini ◽  
Federica Pecci ◽  
Valeria Cognigni ◽  
Veronica Agostinelli ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Serum Albumin ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Objective Response ◽  
Progression Free Survival ◽  
Small Cell ◽  
Albumin Concentration ◽  
Small Cell Lung ◽  
First Line

Background: The Gustave Roussy Immune (GRIm)-Score takes into account neutrophil-to-lymphocyte ratio (NLR), serum albumin concentration and lactate dehydrogenase (LDH) and its prognostic value has been investigated in patients treated with immune check-point inhibitors (ICIs). To further assess the prognostic and predictive value of baseline GRIm-Score (GRImT0) in advanced non-small cell lung cancer (aNSCLC) patients, we separately investigated two cohorts of patients treated with first-line pembrolizumab or chemotherapy. We also investigated whether GRIm-Score at 45 days since treatment initiation (GRImT1) and GRIm-Score difference between the two timepoints may better predict clinical outcomes (GRImΔ = GRImT0 − GRImT1). Methods: We retrospectively evaluated 222 aNSCLC patients: 135 treated with pembrolizumab and 87 treated with chemotherapy as the first-line regimen. NLR, serum albumin and LDH concentrations were assessed at T0 and at T1. According to the GRIm-Score, patients were assigned 1 point if they had NLR > 6, LDH > upper limit normal or albumin < 3.5 g/dL. Patients with a GRIm-Score < 2 were considered as having a low Score. Results: In both cohorts, no difference in terms of overall survival (OS) between patients with low and high GRImT0 was found. Otherwise, median OS and progression free survival (PFS) of the low GRImT1 group were significantly longer than those of the high GRImT1 group in pembrolizumab-treated patients, but not in the CHT cohort (pembrolizumab cohort: low vs. high; median OS not reached vs. 9.2 months, p = 0.004; median PFS 10.8 vs. 2.3 months, p = 0.002). Patients receiving pembrolizumab with stable/positive GRImΔ had better OS (median OS not reached vs. 12.0 months, p < 0.001), PFS (median PFS 20.6 vs. 2.6 months, p < 0.001) and objective response rate (58.2% vs. 7.6%, p = 0.003) compared to patients with negative GRImΔ. Conclusion: Our data shown that GRImT1 and GRImΔ are more reliable peripheral blood biomarkers of outcome compared to GRImT0 in aNSCLC patients treated with pembrolizumab and might represent useful biomarkers to drive clinical decisions in this setting.

scholarly journals Carboplatin and Paclitaxel in Combination With Either Vorinostat or Placebo for First-Line Therapy of Advanced Non–Small-Cell Lung Cancer

2010 ◽  
Vol 28 (1) ◽  
pp. 56-62 ◽  
Author(s):  
Suresh S. Ramalingam ◽  
Michael L. Maitland ◽  
Paul Frankel ◽  
Athanassios E. Argiris ◽  
Marianna Koczywas ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Response Rate ◽  
Area Under The Curve ◽  
Progression Free Survival ◽  
Small Cell ◽  
Controlled Study ◽  
Small Cell Lung ◽  
Anticancer Effects

Purpose Vorinostat, a histone deacetylase inhibitor, exerts anticancer effects by both histone and nonhistone–mediated mechanisms. It also enhances the anticancer effects of platinum compounds and taxanes in non–small-cell lung cancer (NSCLC) cell lines. This phase II randomized, double-blinded, placebo-controlled study evaluated the efficacy of vorinostat in combination with carboplatin and paclitaxel in patients with advanced-stage NSCLC. Patients and Methods Patients with previously untreated stage IIIB (ie, wet) or IV NSCLC were randomly assigned (2:1) to carboplatin (area under the curve, 6 mg/mL × min) and paclitaxel (200 mg/m2 day 3) with either vorinostat (400 mg by mouth daily) or placebo. Vorinostat or placebo was given on days 1 through 14 of each 3-week cycle to a maximum of six cycles. The primary end point was comparison of the response rate. Results Ninety-four patients initiated protocol therapy. Baseline patient characteristics were similar between the two arms. The median number of cycles was four for both treatment arms. The confirmed response rate was 34% with vorinostat versus 12.5% with placebo (P = .02). There was a trend toward improvement in median progression-free survival (6.0 months v 4.1 months; P = .48) and overall survival (13.0 months v 9.7 months; P = .17) in the vorinostat arm. Grade 4 platelet toxicity was more common with vorinostat (18% v 3%; P < .05). Nausea, emesis, fatigue, dehydration, and hyponatremia also were more frequent with vorinostat. Conclusion Vorinostat enhances the efficacy of carboplatin and paclitaxel in patients with advanced NSCLC. HDAC inhibition is a promising therapeutic strategy for treatment of NSCLC.

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