A randomized phase III study comparing carboplatin with nab-paclitaxel versus docetaxel for elderly patients with squamous-cell lung cancer: Capital study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9031-9031
Author(s):  
Yoichiro Hamamoto ◽  
Yoshihito Kogure ◽  
Akiko Kada ◽  
Hiroya Hashimoto ◽  
Shinji Atagi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Trials ◽  
Adverse Events ◽  
Elderly Patients ◽  
Cell Lung Cancer ◽  
Primary Endpoint ◽  
Objective Response Rate ◽  
Response Rate ◽  
Objective Response ◽  
Phase Iii

9031 Background: Cytotoxic monotherapy is one of the standard treatments for elderly patients with advanced non-small cell lung cancer (NSCLC). Carboplatin plus nab-paclitaxel demonstrated significantly higher objective response rate (ORR) than carboplatin plus paclitaxel in patients with squamous histology and could improve overall survival (OS) in patients aged ≥70 years. Here, we compared carboplatin plus nab-paclitaxel with docetaxel in elderly patients with squamous NSCLC. Methods: The CAPITAL study is a multicenter, open-label, phase 3, randomized trial at 92 institutions in Japan. Eligible patients had advanced squamous NSCLC with no prior systemic chemotherapy, aged ≥70 years, and had an ECOG performance status of 0 or 1. Patients were randomized 1:1 to docetaxel 60 mg/m2 (D arm) or carboplatin AUC 6 mg/mL/min plus nab-paclitaxel 100 mg/m2 weekly (nab-PC arm) for each 21-day cycle. The primary endpoint was OS. This trial is registered with the UMIN Clinical Trials Registry (UMIN000019843) and the Japan Registry of Clinical Trials (jRCTs041180110). Results: Between December 2015 and August 2020, 196 patients were randomly assigned to the two treatment arms (D arm, n=98; nab-PC arm, n=98). The median follow-up and age were 11.5 months and 76 years (range: 70–88 years), respectively, and 87% of the patients were male. After the planned interim analysis, the independent data monitoring committee confirmed that the study met the primary endpoint of improved OS in August 2020, and this report represents the final analysis. The nab-PC arm showed significant superiority in OS versus the D arm (hazard ratio [HR], 0.52; 90% CI, 0.38-0.70; median, 16.9 vs. 10.9 months; p<0.001). There were also significant improvements in progression-free survival (median, 5.8 vs. 4.0 months; HR, 0.42; 95% CI, 0.30-0.58; p<0.001) and objective response rate (66.3 vs. 28.0 %; p<0.001) in the nab-PC arm versus the D arm. The most common grade 3 or 4 adverse events were leukopenia (46.3 %), neutropenia (63.2 %), and anemia (38.9 %) in the nab-PC arm, and leukopenia (56.7 %), neutropenia (77.3 %), and febrile neutropenia (17.5 %) in the D arm. As notable adverse events, grade ≥2 sensory peripheral neuropathy was observed in 15 (15.8%) and 1 (1.0%) patient in the nab-PC and D arms, respectively. Moreover, serious treatment-related adverse events and treatment-related deaths occurred in 14 (14.7%) and 12 (12.4%) patients and in two and one patient in the nab-PC and D arms, respectively. Conclusions: The nab-PC arm had a significantly improved OS than the D arm among elderly patients with squamous NSCLC. Carboplatin plus nab-paclitaxel became a new standard treatment for these patients. Clinical trial information: UMIN000019843.

Crizotinib Versus Chemotherapy on ALK-positive NSCLC: A Systematic Review of Efficacy and Safety

2018 ◽  
Vol 19 (1) ◽  
pp. 41-49 ◽  
Author(s):  
Mingxia Wang ◽  
Guanqi Wang ◽  
Haiyan Ma ◽  
Baoen Shan
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Adverse Events ◽  
Objective Response Rate ◽  
Retrospective Studies ◽  
Response Rate ◽  
Objective Response ◽  
Treated Group ◽  
Efficacy And Safety ◽  
Alk Positive

Introduction: Crizotinib was approved to treat anaplastic lymphoma kinase (ALK)- positive non-small cell lung cancer (NSCLC) by the Food and Drug Administration in 2011.We conducted a systematic review of clinical trials and retrospective studies to compare the efficacy and safety of crizotinib with chemotherapy. </P><P> Methods: We searched electronic databases from inception to Dec. 2016. Clinical trials and retrospective studies regarding crizotinib and crizotinib versus chemotherapy in treatment of NSCLC were eligible. The primary outcomes were the objective response rate (ORR) and disease control rate (DCR). Results: Nine studies (five clinical trials and four retrospective studies) including 729 patients met the inclusion criteria. Crizotinib treatment revealed 1-year OS of 77.1% and PFS of 9.17 months. And crizotinib had a better performance than chemotherapy in ORR (OR: 4.97, 95%CI: 3.16 to 7.83, P<0.00001, I2=35%). DCR revealed superiority with crizotinib than chemotherapy (OR: 3.42, 95% CI: 2.33 to 5.01, P<0.00001, I2=0%). PR (partial response) were significant superior to that of chemotherapy through direct systematic review. No statistically significant difference in CR (complete response) was found between crizotinib-treated group and chemotherapy-treated group. Regarding SD (stable disease), chemotherapy-treated group had a better performance than crizotinib-treated group. Common adverse events associated with crizotinib were visual disorder, gastrointestinal side effects, and elevated liver aminotransferase levels, whereas common adverse events with chemotherapy were fatigue, nausea, and hematologic toxicity. This systematic review revealed improved objective response rate and increased disease control rate in crizotinib group comparing with chemotherapy group. Crizotinib treatment would be a favorable treatment option for patients with ALK-positive NSCLC. ALK inhibitors may have future potential applications in other cancers driven by ALK or c-MET gene mutations.

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 Randomized, Phase III Trial of First-Line Figitumumab in Combination With Paclitaxel and Carboplatin Versus Paclitaxel and Carboplatin Alone in Patients With Advanced Non–Small-Cell Lung Cancer

2014 ◽  
Vol 32 (19) ◽  
pp. 2059-2066 ◽  
Author(s):  
Corey J. Langer ◽  
Silvia Novello ◽  
Keunchil Park ◽  
Maciej Krzakowski ◽  
Daniel D. Karp ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Objective Response ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
First Line ◽  
Serious Adverse Events

Purpose Figitumumab (CP-751,871), a fully human immunoglobulin G2 monoclonal antibody, inhibits the insulin-like growth factor 1 receptor (IGF-1R). Our multicenter, randomized, phase III study compared figitumumab plus chemotherapy with chemotherapy alone as first-line treatment in patients with advanced non–small-cell lung cancer (NSCLC). Patients and Methods Patients with stage IIIB/IV or recurrent NSCLC disease with nonadenocarcinoma histology received open-label figitumumab (20 mg/kg) plus paclitaxel (200 mg/m2) and carboplatin (area under the concentration-time curve, 6 mg · min/mL) or paclitaxel and carboplatin alone once every 3 weeks for up to six cycles. The primary end point was overall survival (OS). Results Of 681 randomly assigned patients, 671 received treatment. The study was closed early by an independent Data Safety Monitoring Committee because of futility and an increased incidence of serious adverse events (SAEs) and treatment-related deaths with figitumumab. Median OS was 8.6 months for figitumumab plus chemotherapy and 9.8 months for chemotherapy alone (hazard ratio [HR], 1.18; 95% CI, 0.99 to 1.40; P = .06); median progression-free survival was 4.7 months (95% CI, 4.2 to 5.4) and 4.6 months (95% CI, 4.2 to 5.4), respectively (HR, 1.10; P = .27); the objective response rates were 33% and 35%, respectively. The respective rates of all-causality SAEs were 66% and 51%; P < .01). Treatment-related grade 5 adverse events were also more common with figitumumab (5% v 1%; P < .01). Conclusion Adding figitumumab to standard chemotherapy failed to increase OS in patients with advanced nonadenocarcinoma NSCLC. Further clinical development of figitumumab is not being pursued.

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.

Phase III randomized trial of sunitinib malate (SU11248) versus interferon-alfa (IFN-α) as first-line systemic therapy for patients with metastatic renal cell carcinoma (mRCC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. LBA3-LBA3 ◽  
Author(s):  
R. J. Motzer ◽  
T. E. Hutson ◽  
P. Tomczak ◽  
M. D. Michaelson ◽  
R. M. Bukowski ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Objective Response Rate ◽  
Response Rate ◽  
Objective Response ◽  
Third Party ◽  
Phase Iii ◽  
Rank Test ◽  
Phase Ii Trials ◽  
First Line ◽  
Independent Review

LBA3 Background: Two multicenter phase II trials of 2nd line monotherapy with sunitinib (SU11248) in patients (pts) with mRCC showed a response rate of approximately 40% (JCO 2006;24:16–24; Proc ASCO 23, 380s). This international, randomized phase III trial compared the efficacy and safety of sunitinib to IFN-α in treatment naïve pts with mRCC. Methods: Untreated pts with clear-cell mRCC were randomized 1:1 to receive sunitinib (6-week cycles: 50 mg orally once daily for 4 weeks, followed by 2 weeks off) or IFN-α (6-week cycles: subcutaneous injection 9 MU given three times weekly). The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate, overall survival, and adverse events. Based on a planned sample size of 690 patients, the trial was designed to have 90% power to detect a 35% improvement in median PFS from 20 weeks to 27 weeks (4.6 months to 6.2 months; 2-sided unstratified log-rank test; significance level 0.05). Results of a planned analysis on the primary endpoint, PFS, are presented in this report. Results: From Aug 2004 to Oct 2005, 750 patients were randomized: 375 to sunitinib, 375 to IFN-α. Baseline characteristics were well balanced, and included pooled median age = 60 and prior nephrectomy = 90%. Median PFS assessed by third-party independent review was 47.3 weeks (95% CI 40.9, not yet reached) for sunitinib vs. 24.9 weeks (95% CI 21.9, 37.1) for IFN-α [hazard ratio 0.394 (95% CI 0.297, 0.521) (p < 0.000001)]. The objective response rate by third-party independent review was 24.8% (95% CI 19.7, 30.5) for sunitinib vs. 4.9% (95% CI 2.7, 8.1) for IFN-α (p < 0.000001). The objective response rate by investigator assessment was 35.7% (95% CI 30.9, 40.8) for sunitinib vs. 8.8% (95% CI 6.1, 12.1) for IFN-α (p < 0.000001). 632 pts (85%) are alive, with 49 deaths on sunitinib arm and 65 deaths on IFN-α arm. 8% withdrew from the study due to adverse event on sunitinib arm vs. 13% on IFN-α arm. Conclusions: These results demonstrate a statistically significant improvement in PFS and objective response rate for sunitinib over IFN-α in first-line treatment of pts with mRCC. [Table: see text]

MK-6482, a hypoxia-inducible factor 2α inhibitor (HIF-2α), versus everolimus in heavily pretreated, immune checkpoint–inhibitor-resistant, advanced clear cell renal cell carcinoma (ccRCC): Phase III study.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. TPS368-TPS368
Author(s):  
Toni K. Choueiri ◽  
Laurence Albiges ◽  
Li Fan ◽  
Rodolfo F. Perini ◽  
Donna Vickery ◽  
...  
Keyword(s):  
Adverse Events ◽  
Objective Response Rate ◽  
Response Rate ◽  
Cox Regression ◽  
Objective Response ◽  
Locally Advanced ◽  
Phase Iii ◽  
Controlled Study ◽  
Patient Reported ◽  
Metastatic Rcc

TPS368 Background: In ccRCC, HIF-2α is involved in the activation of genes such as VEGFA, cyclin D1, and CXCR4, which are associated with angiogenesis, tumor progression, and metastasis. HIF-2α can accumulate and be overactivated due to the inactivation of the Von Hippel-Lindau ( VHL) tumor suppressor gene, which occurs in most RCC cases. MK-6482 is a potent and selective small molecule inhibitor of HIF-2α that has shown antitumor activity in a phase I/II study in patients with pretreated, advanced ccRCC (NCT02974738). In the study, the objective response rate was 24%, the disease control rate was 80%, and the safety profile was acceptable. Methods: A phase III, open-label, multicenter, randomized, active-controlled study (NCT04195750) will evaluate the efficacy and safety of MK-6482 versus everolimus as second- to third-line therapy in advanced ccRCC. Eligibility criteria include age ≥18 years; unresectable, locally advanced, or metastatic ccRCC; measurable disease per RECIST v1.1; and a history 1 to 3 systemic regimens for locally advanced or metastatic RCC—including at least 2 doses of a PD-L1 inhibitor and a VEGF-targeted therapy alone or in combination, which resulted in progression. Exclusion criteria include diagnosis of hypoxia defined by pulse oximetry <92% at rest or requiring supplemental oxygen, prior HIF or mTOR inhibitor therapy, kinase inhibitors within 2 weeks of randomization and any systemic anticancer antibody within 4 weeks, and known central nervous system metastases and/or carcinomatous meningitis. The study will enroll approximately 736 patients, who will be randomly assigned 1:1 to MK-6482 120 mg or everolimus 10 mg, both orally once daily until documented disease progression, withdrawal of consent, or other discontinuation event. Stratification factors for this study are International Metastatic RCC Database prognostic scores (0 versus 1-2 versus 3-6) and the number of prior anti-VEGF–targeted therapies received for advanced RCC (1 versus 2-3). The planned imaging (CT/MRI) for response evaluation per RECIST v1.1 by blinded independent central review is as follows: imaging at week 8 from the date of randomization, then every 8 weeks through week 49, and every 12 weeks thereafter. Adverse events will be monitored throughout the study and for 30 days after treatment (90 days for serious adverse events). Progression-free survival per RECIST v1.1 and overall survival will be the dual primary endpoints. Objective response rate, duration of response, patient-reported outcomes, and safety will be secondary endpoints. Event rates over time will be summarized using the Kaplan-Meier method, and hazard ratios will be estimated using a stratified Cox regression model. Stratified Miettinen and Nurminen method will be used for analysis of ORR. Recruitment began in December 2019. Clinical trial information: NCT04195750 .

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.

Phase II study of vinorelbine plus carboplatin with concurrent radiotherapy in elderly patients with non-small cell lung cancer

2019 ◽  
Vol 50 (3) ◽  
pp. 318-324
Author(s):  
Masafumi Yamaguchi ◽  
Hideki Hirata ◽  
Noriyuki Ebi ◽  
Jun Araki ◽  
Takashi Seto ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Elderly Patients ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Concurrent Chemoradiotherapy ◽  
Response Rate ◽  
Objective Response ◽  
Locally Advanced ◽  
Small Cell ◽  
Small Cell Lung

Abstract Objective Concurrent chemoradiotherapy is the standard treatment for locally advanced non-small cell lung cancer. In the current aging society, the establishment of an ideal treatment strategy for locally advanced non-small cell lung cancer in the elderly is warranted. To assess the efficacy of concurrent chemoradiotherapy with carboplatin and vinorelbine in elderly patients with locally advanced non-small cell lung cancer. Purpose To assess the efficacy of concurrent chemoradiotherapy with carboplatin and vinorelbine in elderly patients with locally advanced non-small cell lung cancer. Methods This multicenter, phase II study included patients with physiologically or medically unresectable stage I-III NSCLC, who were ≥70 years old. The patients received carboplatin (AUC 2) and vinorelbine (15 mg/m2) both on day 1, 8, 22 and 29 concurrently with radiotherapy (2.0 Gy/day, 30 fractions, total 60 Gy). The primary endpoint was the objective response rate. The secondary endpoints were the progression-free survival, overall survival and the incidence of adverse events. Results 50 patients were accrued (42 men and 8 women). The median age was 77 years (range, 70–89 years) and the clinical stage was I/II/III in 3/7/40, respectively. Forty-seven patients completed the planned treatment. The response was complete remission in 4, partial response in 31, stable disease in 12 and progressive disease in 3, giving an objective response rate of 70% (95% confidence interval: 55.4–82.1). Frequent high Grade 3 or higher adverse events were hematologic, but no treatment deaths were noted. The median and 2-year progression-free survival were 8.4 months and 21.1% (95% confidence interval: 9.5–32.7%), respectively, and the median and 2-year overall survival were 15.4 months and 41.1% (95% confidence interval: 27.0–55.2), respectively. Conclusion Concurrent chemoradiotherapy with carboplatin and vinorelbine showed an acceptable objective response rate and safety in elderly patients.

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