Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase II Study of Fruquintinib After Two Prior Chemotherapy Regimens in Chinese Patients With Advanced Nonsquamous Non‒Small-Cell Lung Cancer

2018 ◽  
Vol 36 (12) ◽  
pp. 1207-1217 ◽  
Author(s):  
Shun Lu ◽  
Jianhua Chang ◽  
Xiaoqing Liu ◽  
Jianhua Shi ◽  
You Lu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Growth Factor ◽  
Objective Response Rate ◽  
Response Rate ◽  
Objective Response ◽  
Small Cell ◽  
Small Cell Lung ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Multicenter Phase

Purpose Patients with advanced non‒small-cell lung cancer (NSCLC) who fail two lines of chemotherapy have unmet medical needs. The kinase inhibitor fruquintinib selectively targets vascular endothelial growth factor receptors and, hence, tumor angiogenesis and lymphogenesis. This randomized, double-blind, placebo-controlled, multicenter phase II trial evaluated the efficacy and safety of fruquintinib in patients with advanced nonsquamous NSCLC who experienced disease progression after second-line chemotherapy. Patients and Methods Eligible patients were randomly assigned (two to one; stratified by epidermal growth factor receptor status) to receive fruquintinib or placebo, both in combination with best supportive care. Oral fruquintinib (5 mg once daily) was given in 4-week cycles of 3 weeks of treatment followed by 1 week off. Tumor response was assessed using Response Evaluation Criteria in Solid Tumors version 1.1. The primary end point was progression-free survival (PFS) evaluated by a blinded image central review (BICR) committee. Secondary end points included investigator-evaluated PFS, objective response rate, disease control rate, overall survival, and safety. Results Ninety-one patients from 12 hospitals received treatment with fruquintinib (n = 61) or placebo (n = 30). Median PFS was 3.8 months with fruquintinib by both BICR and investigators’ evaluations (hazard ratio by BICR, 0.34; 95% CI, 0.20 to 0.57; P < .001). Three- and 6-month survival rates were 90.2% and 67.2% in the fruquintinib group and 73.3% and 58.8% in the placebo group, respectively. The objective response rate and disease control rate were 13.1% and 60.7% with fruquintinib, compared with 0% and 13.3% with placebo ( P = .041 and < .001), respectively. The most common treatment-emergent adverse events with fruquintinib (≥ grade 3) were hypertension (8.2%), hand-foot syndrome (4.9%), and proteinuria (4.9%). Conclusion Third- and fourth-line fruquintinib for advanced NSCLC was superior to placebo and had an acceptable safety profile.

scholarly journals Disodium Cantharidinate and Vitamin B6 Injection Adjunct with Platinum-Based Chemotherapy for the Treatment of Advanced Non-Small-Cell Lung Cancer: A Meta-Analysis

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Zhichao Wang ◽  
Fanchao Feng ◽  
Qi Wu ◽  
Yihan Jin ◽  
Cheng Gu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Objective Response Rate ◽  
Vitamin B6 ◽  
Response Rate ◽  
Meta Analysis ◽  
Objective Response ◽  
Small Cell ◽  
Karnofsky Performance Score ◽  
Performance Score ◽  
Small Cell Lung

Purpose. Disodium cantharidinate and vitamin B6 (DCVB6) injection is effective and widely used for the clinical treatment of non-small-cell lung cancer (NSCLC). This meta-analysis aimed to provide evidence-based medical data for clinical treatment with DCVB6 injection. Methods. We searched 7 medical databases up to January 2018 for all randomized controlled trials (RCTs) based on DCVB6 injection combined with chemotherapy in patients with NSCLC. A manual search in relevant journals and of relevant literature on other websites was also performed. Data extraction and quality assessment were conducted independently by two reviewers. Subsequently, a meta-analysis was conducted using RevMan 5.3 software. Pooled risk ratio (RR) with 95% confidence interval (CI) was used to evaluate dichotomous and continuous outcomes, respectively. The PROSPERO ID was CRD42018086377. Results. A total of 19 RCTs were included. The results of the meta-analysis indicated that the DCVB6 injection combined with chemotherapy was superior to chemotherapy alone regarding objective response rate (RR=1.58, 95% CI 1.40-1.79), Karnofsky performance score (RR=1.68, 95% CI 1.42-1.99), clinical symptom (RR=1.68, 95% CI 1.44-1.96), white blood cell toxicity (RR=0.36, 95% CI 0.27-0.49), platelet toxicity (RR=0.46, 95% CI 0.33-0.63), and vomiting (RR=0.50, 95% CI 0.37-0.67). Conclusions. The current evidence suggests that DCVB6 injection combined with chemotherapy could increase objective response rate and Karnofsky performance score, improve clinical symptoms, and reduce side effects caused by chemotherapy in patients with NSCLC. However, these results should be carefully interpreted due to the low-quality methodology and the small sample sizes of the trials, and our conclusions should be verified by high-quality, large-scale, double-blinded RCTs.

BEYOND: A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Phase III Study of First-Line Carboplatin/Paclitaxel Plus Bevacizumab or Placebo in Chinese Patients With Advanced or Recurrent Nonsquamous Non–Small-Cell Lung Cancer

2015 ◽  
Vol 33 (19) ◽  
pp. 2197-2204 ◽  
Author(s):  
Caicun Zhou ◽  
Yi-Long Wu ◽  
Gongyan Chen ◽  
Xiaoqing Liu ◽  
Yunzhong Zhu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Objective Response Rate ◽  
Response Rate ◽  
Objective Response ◽  
Small Cell ◽  
Phase Iii ◽  
Chinese Patients ◽  
Small Cell Lung ◽  
First Line

Purpose The phase III BEYOND trial was undertaken to confirm in a Chinese patient population the efficacy seen with first-line bevacizumab plus platinum doublet chemotherapy in globally conducted studies. Patients and Methods Patients age ≥ 18 years with locally advanced, metastatic, or recurrent advanced nonsquamous non–small-cell lung cancer (NSCLC) were randomly assigned to receive carboplatin (area under the curve, 6) intravenously and paclitaxel (175 mg/m2) intravenously (CP) on day 1 of each 3-week cycle, for ≤ six cycles, plus placebo (Pl+CP) or bevacizumab (B+CP) 15 mg/kg intravenously, on day 1 of each cycle, until progression, unacceptable toxicity, or death. The primary end point was progression-free survival (PFS); secondary end points were objective response rate, overall survival, exploratory biomarkers, safety. Results A total of 276 patients were randomly assigned, 138 to each arm. PFS was prolonged with B+CP versus Pl+CP (median, 9.2 v 6.5 months, respectively; hazard ratio [HR], 0.40; 95% CI, 0.29 to 0.54; P < .001). Objective response rate was improved with B+CP compared with Pl+CP (54% v 26%, respectively). Overall survival was also prolonged with B+CP compared with Pl+CP (median, 24.3 v 17.7 months, respectively; HR, 0.68; 95% CI, 0.50 to 0.93; P = .0154). Median PFS was 12.4 months with B+CP and 7.9 months with Pl+CP (HR, 0.27; 95% CI, 0.12 to 0.63) in EGFR mutation–positive tumors and 8.3 and 5.6 months, respectively (HR, 0.33; 95% CI, 0.21 to 0.53), in wild-type tumors. Safety was similar to previous studies of B+CP in NSCLC; no new safety signals were observed. Conclusion The addition to bevacizumab to carboplatin/paclitaxel was well tolerated and resulted in a clinically meaningful treatment benefit in Chinese patients with advanced nonsquamous NSCLC.

Poziotinib for Patients With HER2 Exon 20 Mutant Non–Small-Cell Lung Cancer: Results From a Phase II Trial

2021 ◽  
pp. JCO.21.01113
Author(s):  
Yasir Y. Elamin ◽  
Jacqulyne P. Robichaux ◽  
Brett W. Carter ◽  
Mehmet Altan ◽  
Don L. Gibbons ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Phase Ii ◽  
Objective Response Rate ◽  
Response Rate ◽  
Objective Response ◽  
Small Cell ◽  
Small Cell Lung ◽  
Platinum Based Chemotherapy ◽  
Exon 20

PURPOSE Targeted therapies against non–small-cell lung cancer (NSCLC) harboring HER2 mutations remain an unmet need. In this study, we assessed the efficacy and safety of poziotinib in patients with HER2 exon 20 mutant advanced NSCLC in a single-arm, open-label, phase II study. PATIENTS AND METHODS Patients with advanced HER2 exon 20 mutant NSCLC were enrolled to receive poziotinib at a dose of 16 mg/d for 28-day cycles. The primary end point was objective response rate per RECIST version 1.1. Confirmatory scans were performed at least 28 days from initial radiologic response. RESULTS Thirty patients received poziotinib treatment. At baseline, 90% of patients received prior platinum-based chemotherapy and 53% had two lines or more prior systemic therapies. As of data cutoff on March 1, 2021, the confirmed objective response rate was 27% (95% CI, 12 to 46). Responses were observed across HER2 exon 20 mutation subtypes. The median duration of response was 5.0 months (95% CI, 4.0 to not estimable). The median progression-free survival was 5.5 months (95% CI, 4.0 to 7.0). The median overall survival was 15 months (95% CI, 9.0 to not estimable). The most common grade 3 treatment-related adverse events were skin rash (47%) and diarrhea (20%). There was one possible treatment-related death because of pneumonitis. CONCLUSION Poziotinib showed promising antitumor activity in patients with HER2 exon 20 mutant NSCLC including patients who had previously received platinum-based chemotherapy.

scholarly journals International, Randomized, Placebo-Controlled, Double-Blind Phase III Study of Motesanib Plus Carboplatin/Paclitaxel in Patients With Advanced Nonsquamous Non–Small-Cell Lung Cancer: MONET1

2012 ◽  
Vol 30 (23) ◽  
pp. 2829-2836 ◽  
Author(s):  
Giorgio V. Scagliotti ◽  
Ihor Vynnychenko ◽  
Keunchil Park ◽  
Yukito Ichinose ◽  
Kaoru Kubota ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Growth Factor ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Objective Response ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Double Blind ◽  
Nonsquamous Nsclc

Purpose We evaluated whether motesanib (a selective oral inhibitor of vascular endothelial growth factor receptors 1, 2, and 3; platelet-derived growth factor receptor; and Kit) combined with carboplatin/paclitaxel improved overall survival (OS) versus chemotherapy alone in patients with nonsquamous non–small-cell lung cancer (NSCLC) and in the subset of patients with adenocarcinoma. Patients and Methods Patients with stage IIIB/IV or recurrent nonsquamous NSCLC (no prior systemic therapy for advanced disease) were randomly assigned 1:1 to carboplatin (area under the curve, 6 mg/ml · min) and paclitaxel (200 mg/m2) intravenously for up to six 3-week cycles plus either motesanib 125 mg (arm A) or placebo (arm B) once daily orally. OS was the primary end point. Secondary end points included progression-free survival (PFS), objective response rate (ORR), adverse events (AEs), and association between placental growth factor (PLGF) change and OS. Results A total of 1,090 patients with nonsquamous NSCLC were randomly assigned (arms A/B, n = 541 of 549); of those, 890 had adenocarcinoma (n = 448 of 442). Median OS in arms A and B was 13.0 and 11.0 months, respectively (hazard ratio [HR], 0.90; 95% CI, 0.78 to 1.04; P = .14); median OS for the adenocarcinoma subset was 13.5 and 11.0 months, respectively (HR, 0.88; 95% CI, 0.75 to 1.03; P = .11). In descriptive analyses (arms A v B), median PFS was 5.6 months versus 5.4 months (P = < .001); ORR was 40% versus 26% (P < .001). There was no association between PLGF change and OS in arm A. The incidence of grade ≥ 3 AEs (arms A and B, 73% and 59%, respectively) and grade 5 AEs (14% and 9%, respectively) was higher with motesanib treatment. Conclusion Motesanib plus carboplatin/paclitaxel did not significantly improve OS over carboplatin/paclitaxel alone in patients with advanced nonsquamous NSCLC or in the adenocarcinoma subset.

LUX-Lung 4: A Phase II Trial of Afatinib in Patients With Advanced Non–Small-Cell Lung Cancer Who Progressed During Prior Treatment With Erlotinib, Gefitinib, or Both

2013 ◽  
Vol 31 (27) ◽  
pp. 3335-3341 ◽  
Author(s):  
Nobuyuki Katakami ◽  
Shinji Atagi ◽  
Koichi Goto ◽  
Toyoaki Hida ◽  
Takeshi Horai ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Partial Response ◽  
Small Cell Lung Cancer ◽  
Objective Response Rate ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Acquired Resistance ◽  
Small Cell ◽  
Small Cell Lung

Purpose New molecular targeted agents are needed for patients with non–small-cell lung cancer (NSCLC) who progress while receiving erlotinib, gefitinib, or both. Afatinib, an oral irreversible ErbB family blocker, has preclinical activity in epidermal growth factor receptor (EGFR [ErbB1]) mutant models with EGFR-activating mutations, including T790M. Patients and Methods This was a Japanese single-arm phase II trial conducted in patients with stage IIIB to IV pulmonary adenocarcinoma who progressed after ≥ 12 weeks of prior erlotinib and/or gefitinib. Patients received afatinib 50 mg per day. The primary end point was objective response rate (complete response or partial response) by independent review. Secondary end points included progression-free survival (PFS), overall survival (OS), and safety. Results Of 62 treated patients, 45 (72.6%) were EGFR mutation positive in their primary tumor according to local and/or central laboratory analyses. Fifty-one patients (82.3%) fulfilled the criteria of acquired resistance to erlotinib and/or gefitinib. Of 61 evaluable patients, five (8.2%; 95% CI, 2.7% to 18.1%) had a confirmed objective response rate (partial response). Median PFS was 4.4 months (95% CI, 2.8 to 4.6 months), and median OS was 19.0 months (95% CI, 14.9 months to not achieved). Two patients had acquired T790M mutations: L858R + T790M, and deletion in exon 19 + T790M; they had stable disease for 9 months and 1 month, respectively. The most common afatinib-related adverse events (AEs) were diarrhea (100%) and rash/acne (91.9%). Treatment-related AEs leading to afatinib discontinuation were experienced by 18 patients (29%), of whom four also had progressive disease. Conclusion Afatinib demonstrated modest but noteworthy efficacy in patients with NSCLC who had received third- or fourth-line treatment and who progressed while receiving erlotinib and/or gefitinib, including those with acquired resistance to erlotinib, gefitinib, or both.

Vandetanib Plus Pemetrexed for the Second-Line Treatment of Advanced Non–Small-Cell Lung Cancer: A Randomized, Double-Blind Phase III Trial

2011 ◽  
Vol 29 (8) ◽  
pp. 1067-1074 ◽  
Author(s):  
Richard H. de Boer ◽  
Óscar Arrieta ◽  
Chih-Hsin Yang ◽  
Maya Gottfried ◽  
Valorie Chan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Objective Response Rate ◽  
Response Rate ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Phase Iii ◽  
Second Line ◽  
Small Cell Lung

Purpose Vandetanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor and epidermal growth factor receptor signaling. This randomized, placebo-controlled phase III study assessed the efficacy of vandetanib plus pemetrexed as second-line therapy in advanced non–small-cell lung cancer. Patients and Methods Patients (N = 534) were randomly assigned to receive vandetanib 100 mg/d plus pemetrexed 500 mg/m2 every 21 days (n = 256) or placebo plus pemetrexed (n = 278). Progression-free survival (PFS) was the primary end point; overall survival, objective response rate, disease control rate, time to deterioration of symptoms, and safety were secondary assessments. Results There was no significant difference in PFS between treatment arms (hazard ratio [HR], 0.86; 97.58% CI, 0.69 to 1.06; P = .108). Overall survival was also not significantly different (HR, 0.86; 97.54% CI, 0.65 to 1.13; P = .219). Statistically significant improvements in objective response rate (19% v 8%; P < .001) and time to deterioration of symptoms (HR, 0.71; P = .0052; median, 18.1 weeks for vandetanib and 12.1 weeks for placebo) were observed in patients receiving vandetanib. Adding vandetanib to pemetrexed increased the incidence of some adverse events, including rash, diarrhea, and hypertension, while showing a reduced incidence of nausea, vomiting, anemia, fatigue, and asthenia with no reduction in the dose intensity of pemetrexed. Conclusion This study did not meet the primary end point of statistically significant PFS prolongation with vandetanib plus pemetrexed versus placebo plus pemetrexed. The vandetanib combination showed a significantly higher objective response rate and a significant delay in the time to worsening of lung cancer symptoms versus the placebo arm as well as an acceptable safety profile in this patient population.

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