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.

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.

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.

Phase III randomized trial comparing cisplatin and carboplatin with or without ifosfamide in patients with advanced non-small-cell lung cancer. European Lung Cancer Working Party.

1998 ◽  
Vol 16 (4) ◽  
pp. 1388-1396 ◽  
Author(s):  
J P Sculier ◽  
M Paesmans ◽  
J Thiriaux ◽  
J Lecomte ◽  
G Bureau ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Randomized Trial ◽  
Cell Lung Cancer ◽  
Response Rate ◽  
Objective Response ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Moderate Dose

PURPOSE A phase III randomized trial in patients with advanced non-small-cell lung cancer (NSCLC) was performed to determine if the addition of ifosfamide to moderate-dose cisplatin and carboplatin improved response rate (primary end point) and survival. PATIENTS AND METHODS A total of 529 patients were randomized to receive a combination of moderate-dose carboplatin (200 mg/m2 intravenously [i.v.] on day 1) and cisplatin (30 mg/m2 i.v. on days 2 and 3) with (CCI arm) or without (CC arm) ifosfamide (1.5 g/m2 i.v. on days 1 to 3). There were 248 eligible patients on the CC arm and 257 on the CCI arm, with 220 and 238 patients assessable for response, respectively. All but 23 had stage IV disease with pleural effusion. RESULTS There was a 16% objective response (OR) rate to CC and a 31% OR rate to CCI. That observed difference was highly statistically significant (P < 0.001). Duration of response and survival were not statistically different between arms. The CCI regimen was associated with significantly more acute toxicities: emesis, alopecia, leukopenia, and thrombocytopenia. The frequency of chronic renal, auditive, and peripheral neurologic toxicity was low in both arms (4.6% and 6.6%, respectively, after six courses of chemotherapy). The relative dose-intensity (RDI) of the CCI arm was significantly lower than that of the CC arm. CONCLUSION The addition of ifosfamide to moderate-dose cisplatin and carboplatin significantly improves the antitumoral response rate, but has no apparent effect an survival in advanced NSCLC.

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.

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.

A phase 1b/2 study of napabucasin with weekly paclitaxel in advanced, previously treated non-squamous non-small cell lung cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9052-9052 ◽  
Author(s):  
Carlos Becerra ◽  
Wahid Tewfik Hanna ◽  
Stephen Lane Richey ◽  
Gregory Michael Cote ◽  
Scott Andrew Laurie ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival ◽  
Anti Cancer ◽  
Cancer Activity

9052 Background: Napabucasin is a first-in-class cancer stemness inhibitor, identified by its ability to inhibit STAT3-driven gene transcription and spherogenesis of cancer stem cells (Li et al PNAS 112 (6):1839, 2015). Napabucasin has shown potent synergistic preclinical anti-tumor activity with paclitaxel (PTX). In a phase Ib dose escalation study in patients (pts) with advanced solid tumors, napabucasin plus weekly PTX was well tolerated. A phase II expansion cohort was opened for pts with advanced non-small cell lung cancer (NSCLC). Methods: Pts with metastatic non-squamous NSCLC were enrolled to confirm safety and preliminary anti-cancer activity. Prior platinum-based systemic therapy was required, and patients with an EGFR or ALK mutation required appropriately targeted therapy. Napabucasin was administered orally at a starting dose of 240 or 480 mg BID with PTX 80 mg/m2 IV weekly 3 of every 4 weeks. AEs were evaluated using CTCAE v4.03 and objective assessments were performed every 8 weeks per RECIST 1.1. Results: A cohort of 23 pts with advanced non-squamous NSCLC was evaluated. The median number of prior systemic treatment lines was 3, including taxane-based therapy in 100% and immune checkpoint inhibitor in 48% (n = 11). Treatment was well tolerated; related grade 3 AE included diarrhea (n = 4) and fatigue (n = 1). The objective response rate was 26% (6 partial responses [PR]) and the disease control rate (DCR; proportion with SD at 8 weeks plus PR per RECIST) was 70% (n = 16). Tumor regression, including PR, occurred in 35% (n = 8). The median progression-free survival (mPFS) was 5.4 months, and 43% (n = 10) of pts were alive and free of progression at the 24 week time-point or longer. The median overall survival (mOS) was 11.0 months, and 30% (n = 7) of pts were alive for 52 weeks or longer. Conclusions: Clinical safety and encouraging signs of anti-cancer activity were observed in pts with heavily pretreated non-squamous NSCLC who received napabucasin plus weekly paclitaxel. The objective response rate, progression free survival, and overall survival in this population warrant further clinical evaluation and a controlled phase 2/3 trial (CanStem43L) has been initiated. Clinical trial information: NCT01325441.

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