scholarly journals Randomized Phase II Study of Docetaxel plus Personalized Peptide Vaccination versus Docetaxel plus Placebo for Patients with Previously Treated Advanced Wild Type EGFR Non-Small-Cell Lung Cancer

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Koichi Takayama ◽  
Shunichi Sugawara ◽  
Yasuo Saijo ◽  
Makoto Maemondo ◽  
Atsushi Sato ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Clinical Investigation ◽  
Small Cell ◽  
Rank Test ◽  
Peptide Vaccination ◽  
Small Cell Lung ◽  
Significant Difference ◽  
Previously Treated

Objectives. To evaluate the efficacy and safety of personalized peptide vaccination (PPV) combined with chemotherapy for patients with previously treated advanced non-small-cell lung cancer (NSCLC).Patients and Methods. Previously treated PS0-1 patients with IIIB/IV EGFR (epidermal growth factor receptor) wild genotype NSCLC were randomly assigned to docetaxel (60 mg/m2on Day 1) plus PPV based on preexisting host immunity or docetaxel plus placebo. Docetaxel administration was repeated every 3 weeks until disease progression. Personalized peptides or placebo was injected subcutaneously weekly in the first 8 weeks and biweekly in subsequent 16 weeks. The primary efficacy endpoint was progression-free survival (PFS).Results. PPV related toxicity was grade 2 or less skin reaction. The median PFS for placebo arm and PPV arm was 52 days and 59 days, respectively. There was no significant difference between two arms by log-rank test (p=0.42). Interestingly, PFS and overall survival (OS) in humoral immunological responder were significantly longer than those in nonresponder.Conclusion. PPV did not improve the survival in combination with docetaxel for previously treated advanced NSCLC. However, PPV may be efficacious for the humoral immunological responders and a further clinical investigation is needed.

Pemetrexed versus gefitinib versus erlotinib in previously treated non-small cell lung cancer by retrospective analysis

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19103-e19103
Author(s):  
E. Cho ◽  
J. Hong ◽  
S. Kyung ◽  
Y. Kim ◽  
S. Shim ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Retrospective Analysis ◽  
Cell Lung Cancer ◽  
Performance Status ◽  
Small Cell ◽  
Small Cell Lung ◽  
Folate Supplementation ◽  
Significant Difference ◽  
Previously Treated

e19103 Background: The standards in 2nd-line therapy with advanced non-small cell lung cancer (NSCLC) were erlotinib or pemetrexed as well as docetaxel. To evaluate the efficacies and safeties of pemetrexed, gefitinib, and erlotinib in previously treated NSCLC we analyzed the datas retrospectively. Methods: Eligible patents were 1) histologically confirmed pretreated advanced (stage IIIB or IV) NSCLC, 2) with at least one measurable lesion, 3) age over 18 years, 4) performance status (PS) 0–2, and 5) should never experience other two drugs as previous therapy. Patients of pemetrexed group received IV infusion of 500mg/m2 pemetrexed mixed with normal saline every 3 weeks with vitamin B12 and folate supplementation. Patients of gefitinib group received gefitinib 250mg PO daily and of erlotinib took erlotinib 150mg PO daily. Cycles of IV pemetrexed or taking PO drugs were continued until disease progression or unacceptable toxicity. Results: we analyzed 57 patients (pemetrexed; 20, gefitnib; 20, and erlotinib; 17). The response rates were 5.3%, 25.0%, and 12.5% (P=0.22), and the disease control rate were 5.3%, 40.0%, and 50.0% respectively (P<0.01). Median progression-free survival (PFS) of pemetrexed, gefitinib, and erlotinib were 1.7, 3.5 and 4.4 months (P<0.01) and median overall survival (OS) were 5.6, 21.8 and 21.5 months respectively (P=0.04). In subgroup analysis, patients with non-squamous carcinoma, smokers and good PS (0 or 1) showed longer PFS and OS in gefitinib and erlotinib compared with in pemetrexed. All of these agents showed mild and tolerable toxicity. Conclusions: In retrospective analysis, the patients with gefitinib or erlotinib had longer PFS and OS than pemetrexed, eventhough there was no significant difference for response rate in three group. These results have to confirm by large randomized prospective study because the sample size was small and it was not randomized. No significant financial relationships to disclose.

Molecular Predictors of Outcome With Gefitinib and Docetaxel in Previously Treated Non–Small-Cell Lung Cancer: Data From the Randomized Phase III INTEREST Trial

2010 ◽  
Vol 28 (5) ◽  
pp. 744-752 ◽  
Author(s):  
Jean-Yves Douillard ◽  
Frances A. Shepherd ◽  
Vera Hirsh ◽  
Tony Mok ◽  
Mark A. Socinski ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Copy Number ◽  
Egfr Mutation ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Significant Difference ◽  
Previously Treated

PurposeIn the phase III INTEREST trial, 1,466 pretreated patients with advanced non–small cell lung cancer (NSCLC) were randomly assigned to receive gefitinib or docetaxel. As a preplanned analysis, we prospectively analyzed available tumor biopsies to investigate the relationship between biomarkers and clinical outcomes.MethodsBiomarkers included epidermal growth factor receptor (EGFR) copy number by fluorescent in situ hybridization (374 assessable samples), EGFR protein expression by immunohistochemistry (n = 380), and EGFR (n = 297) and KRAS (n = 275) mutations.ResultsFor all biomarker subgroups analyzed, survival was similar for gefitinib and docetaxel, with no statistically significant differences between treatments and no significant treatment by biomarker status interaction tests. EGFR mutation–positive patients had longer progression-free survival (PFS; hazard ratio [HR], 0.16; 95% CI, 0.05 to 0.49; P = .001) and higher objective response rate (ORR; 42.1% v 21.1%; P = .04), and patients with high EGFR copy number had higher ORR (13.0% v 7.4%; P = .04) with gefitinib versus docetaxel.ConclusionThese biomarkers do not appear to be predictive factors for differential survival between gefitinib and docetaxel in this setting of previously treated patients; however, subsequent treatments may have influenced the survival results. For secondary end points of PFS and ORR, some advantages for gefitinib over docetaxel were seen in EGFR mutation–positive and high EGFR copy number patients. There was no statistically significant difference between gefitinib and docetaxel in biomarker-negative patients. This suggests gefitinib can provide similar overall survival to docetaxel in patients across a broad range of clinical subgroups and that EGFR biomarkers such as mutation status may additionally identify which patients are likely to gain greatest PFS and ORR benefit from gefitinib.

Initial safety and efficacy results of erlotinib in previously treated patients with advanced non-small cell lung cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18183-18183
Author(s):  
S. Zhou ◽  
C. Zhou ◽  
L. Yan ◽  
Q. Xu ◽  
J. Xu
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Smoking Status ◽  
Small Cell ◽  
Small Cell Lung ◽  
Significant Difference ◽  
Previously Treated ◽  
Nsclc Patients ◽  
Severe Rash

18183 Background: Erlotinib is an orally available selective HER1/EGFR tyrosine kinase inhibitor. In the BR.21 trial, erlotinib significantly improved survival and quality of life in non-small cell lung cancer(NSCLC) patients (pts). The study evaluated the initial efficacy and safety of erlotinib in previously treated advanced or metastatic NSCLC patients in Shanghai, China. Methods: Eligibility criteria included stage IIIb/IV or recurrent NSCLC pts who failed from prior chemotherapy, PS = 0–2, weight loss less than 5%, and no urgent symptoms. Pts received oral erlotinib 150 mg po/day until objective or symptomatic progression. Results: 50 pts were enrolled from Oct 1 to Sept 30. Demographics: M 68%/F 32%; median age 55 y [range 28–68]; stage IV 86%; PS 0/1/2:2 (4%)/44 (88%)/4 (8%); adenocarcinoma/non-adenocarcinoma 39 (78%)/11 (22%); smoking status: 26 (52%) /no 24 (48%). The major toxicity was rash: 48 (96%), 10 (20%) of them are grade 3/4; other toxicity included grade 1/2 diahhrea: 5 (10%); grade 1/2 liver dysfunction: 4 (8%); grade 2 leucocytopenia: 2 (4%); grade 1 thrombocytopenia: 1(2%); fatigue and dyspnea. 3 patients discontinued for dyspnea, pneumonitis and fatigue respectively. No pts had pulmonary fibrosis and dose reduction. 47 pts were followed long enough for efficacy evaluation, which indentified 18 (38%) with PR, 21 (45%) with SD, 8 (17%) with PD. Subgroup analysis showed the resposes to erlotinib have no relation with gender, age, smoking status, performance status, histology and stages, however, significant difference existed in the subgroup patients with severe rash and less symptoms such as dyspnea and fatigue ( Table 1 ). Conclusions: Erlotinib is active and well tolerated in patients with advanced NSCLC failed to previously chemotherapy. Preliminary results suggest patients with severe rash, less dyspnea and fatigue are accociated with better response. The study in ongoing. Table 1 Response of erlotinib in advanced treated NSCLC pts. * P values less than 0.05. [Table: see text] No significant financial relationships to disclose.

Prognostic role of filgrastim and derived neutrophil-to-lymphocyte ratio (dNLR) in the effectiveness of PD1/PDL1 inhibitors in previously treated non-small cell lung cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21729-e21729
Author(s):  
Juan Francisco Marin Pozo ◽  
Carmen Lucia Muñoz Cid ◽  
Macarena Merino Almazán ◽  
Raquel Claramunt García ◽  
Elvira Marin Caba ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Lymphocyte Ratio ◽  
Platinum Based Chemotherapy ◽  
Significant Difference ◽  
Previously Treated ◽  
The Mean

e21729 Background: A neutrophil/lymphocyte ratio (NLR)> 5 or its derivative (dNLR)> 3 have been proposed as a prognostic factor for non-effectiveness of nivolumab in non-small-cell lung cancer (NSCLC). Filgrastim (GSGF) increases the absolute counts of neutrophils in patients (pts) with neutropenia. The aim of this study is to determine whether the use of GSGF, during the first line therapy of nSCLC, influences the effectiveness of the anti-PD1/PDL1 inhibitors (aPD1-i) used in subsequent line. Methods: We designed a single center, observational and retrospective study. We included NSCLC pts treated with Nivolumab (NIV), Pembrolizumab (PEM) or Atezolizumab (ATE) between January-16 and November-19 after primary platinum-based chemotherapy at one hospital from south Spain. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Results were assessed using Kaplan-Meier method for GSGF-use stratified by NLR, dNLR, or aPD1-i. Results: 79 pts were enrolled (91% men), mean age was 66.7 years, 78.8% of pts had ECOG = 0-1. NIV was used at 55.7%, ATE 25.3% and PEM 19.0% of pts. 50.6 % of tumors were squamous histology. GSGF was used at 19 pts (24.1%). The mean WBC at the start of therapy with aPD1-I was 9300 cell/µL (sd=3900), range 3600-25800 cell/µL. NLR was less than 5 in 46 pts (58.2%) and dNLR was less than 3 in 51 pts (64.6%). The mean time from the start of line previously to start the treatment with aPD1-i was 9.7 months (sd=8.6). The median for treatment duration was 4.1 months [IC 95%; 2.3-5.8].OS was 7.3 months [IC 95%:3.4-11.3] and PFS was 4.4 months [IC95%:2.3-6.5]. We found statistically significant difference in OS between patients with dNLR <3, median 13.9 months [IC95%; 5.4-22.4] vs patients with dNLR> 3, median 3.6 months [IC95%; 2.4-4.7], p=0.037. The median OS was higher in pts GSGF-treated (6.1 months) vs pts no GSGF-treated (3.3 months), p=0.347, no reaching statistical significance. No difference was found in OS by NLR. The analysis for OS by GSGF use stratified by dNLR is shown in the table. Conclusions: The effectiveness of aPD1-i in nSCLC patients previously treated and with dNLR>3, a priori poor prognosis, is greater in the group of patients treated with GSGF, reaching OS like pts with dNLR <3. [Table: see text]

scholarly journals Liquid Biopsy Testing Can Improve Selection of Advanced Non-Small-Cell Lung Cancer Patients to Rechallenge With Gefitinib

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1431 ◽  
Author(s):  
Abate ◽  
Pasquale ◽  
Sacco ◽  
Piccirillo ◽  
Morabito ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
First Generation ◽  
Kinase Inhibitor ◽  
Small Cell ◽  
Rank Test ◽  
Small Cell Lung ◽  
Single Nucleotide Variants ◽  
Significant Difference

The ICARUS trial is a phase II, open label, multicenter, single arm study conducted to investigate the efficacy, safety, and tolerability of a rechallenge treatment with the first-generation tyrosine kinase inhibitor (TKI) gefitinib in advanced non-small-cell lung cancer (NSCLC) patients carrying activating mutations of the epidermal growth factor receptor (EGFR). The ICARUS trial enrolled 61 patients who were rechallenged with gefitinib at progression after second-line chemotherapy. Serum-derived circulating cell-free DNA (cfDNA) collected before the rechallenge from a cohort of 29 patients, was retrospectively analyzed for the EGFR exon 19 deletions and for the p.L858R and p.T790M single nucleotide variants (SNV). The analysis of cfDNA detected the same EGFR activating mutation reported in the tumor tissue in 20/29 patients, with a sensitivity of 69%. Moreover, a p.T790M variant was found in 14/29 patients (48.3%). The median progression-free survival (PFS) was 2.7 months for p.T790M positive patients (CI 95% 1.4–3.1 months) versus 3.5 months for the p.T790M negative patients (CI 95% 1.6–5.3 months), resulting in a statistically significant difference (Long rank test p = 0.0180). These findings confirmed the role of the p.T790M mutation in the resistance to first-generation TKIs. More importantly, our data suggest that TKI rechallenge should be guided by biomarker testing.

scholarly journals Comparison of efficiency and toxicity of two chemotherapy protocols in treatment of advanced non-small cell lung cancer

2011 ◽  
Vol 64 (7-8) ◽  
pp. 368-372 ◽  
Author(s):  
Alma Mekic-Abazovic ◽  
Ibrahim Sisic ◽  
Vladimir Kovcin ◽  
Hakija Beculic ◽  
Senad Dervisevic ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Tumour Response ◽  
Progression Free Survival ◽  
Small Cell ◽  
Rank Test ◽  
Small Cell Lung ◽  
Free Survival ◽  
Significant Difference

Introduction. This study was aimed at comparing the efficiency and tolerability of two reference protocols Cisplatin and Etoposide and Cisplatin and Vinorelbine in advanced Non-Small Cell Lung Cancer. Material and Methods. A total of 60 patients (two groups consisting of 30 patients) were treated for advanced Non-Small Cell Lung Cancer during the period from January to December 2005 according to the reference protocols (Cisplatin 100mg/m2 D1; Vinorelbine 30 mg/m2 D1, D8 on 4 weeks) and (Cisplatin 100 mg/m2 D1; Etoposide 100 mg/m2 D1, D3, D5 on 4 weeks) at the Department of Oncology of KBC ?Bezanijska kosa?. All patients were analyzed for tumour response, progression free survival as well as for toxicity. X2 test, Kaplan Meiers curves and Log rank test were used for statistical analysis. Results. Although the recorded response rates were a bit lower than in previously published trials, they were not significantly different p=0.485. No statistically significant difference was recorded in either progression free survival or overall survival. The chemotherapeutical Cisplatin/Etoposide protocol proved to be more toxic both in hematologic (3% vs. 10%) and total toxicities (p=0.047). Conclusion. Our study proved both protocols to have equivalent efficacy. However, the Cisplatin, Vinorelbine protocol could be recommended because of its less expressed toxic effects.

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