A phase Ib/II trial of lenvatinib plus pembrolizumab in non-small cell lung cancer.

2019 ◽  
Vol 37 (8_suppl) ◽  
pp. 16-16 ◽  
Author(s):  
Marcia S. Brose ◽  
Nicholas J. Vogelzang ◽  
Christopher DiSimone ◽  
Sharad K. Jain ◽  
Donald A. Richards ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Objective Response ◽  
Small Cell ◽  
Clinical Activity ◽  
Phase 2 ◽  
Small Cell Lung ◽  
Previously Treated ◽  
Grade 3

16 Background: Lenvatinib (LEN) is a multikinase inhibitor of VEGFR 1−3, FGFR 1−4, PDGFRα, RET, and KIT. Pembrolizumab (PEM), an anti-PD-1 antibody, is an approved monotherapy for previously treated patients (pts) with PD-L1 (+) (tumor proportion score ≥1%) metastatic non-small cell lung cancer (mNSCLC; objective response rate [ORR] 18%). We report interim results of an ongoing phase 1b/2 trial of LEN + PEM in pts with solid tumors, focusing on the mNSCLC cohort. Methods: In this multicenter, open-label study (NCT02501096), pts with measurable, confirmed mNSCLC, ECOG PS ≤1, ≤ 2 prior systemic therapies (phase 2 only) received oral LEN (20 mg/day) and PEM (200 mg Q3W, IV). Pts were not preselected by PD-L1 status. The phase 2 primary end point was ORR at 24 weeks (ORRWK24) by investigator-assessed immune-related RECIST (irRECIST). Secondary end points included ORR, progression-free survival (PFS) and duration of response (DOR). Results: At data cutoff (March 1, 2018), 21 pts were enrolled: 9 (43%) PD-L1(+), 5 (24%) PD-L1(-), and 7 (33%) not tested. Pts were treatment-naïve (14%); or had 1 (33%), 2 (48%), or ≥3 (5%) prior lines of systemic therapy. ORRWK24 was 33.3% (95% CI, 14.6–57.0); other efficacy outcomes are summarized in the table. Grade 3 and 4 treatment-related adverse events (TRAEs) occurred in 48% and 5% (increased aspartate aminotransferase) of pts. There was 1 fatal TRAE (exsanguination; “possibly related” to study treatment). The most common grade 3 TRAEs were hypertension (24%), fatigue (14%), diarrhea (14%), proteinuria (10%), and arthralgia (10%). Conclusions: LEN + PEM showed promising clinical activity and a manageable safety profile in previously treated pts with mNSCLC who were not preselected for PD-L1 status. Further study is warranted.[Table: see text]

Phase II Study of Pemetrexed and Carboplatin Plus Bevacizumab With Maintenance Pemetrexed and Bevacizumab As First-Line Therapy for Nonsquamous Non–Small-Cell Lung Cancer

2009 ◽  
Vol 27 (20) ◽  
pp. 3284-3289 ◽  
Author(s):  
Jyoti D. Patel ◽  
Thomas A. Hensing ◽  
Alfred Rademaker ◽  
Eric M. Hart ◽  
Matthew G. Blum ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Objective Response ◽  
Small Cell ◽  
Phase Iii ◽  
Hematologic Toxicity ◽  
Small Cell Lung ◽  
Time Curve ◽  
Grade 3

PurposeThis study evaluated the efficacy and safety of pemetrexed, carboplatin, and bevacizumab followed by maintenance pemetrexed and bevacizumab in patients with chemotherapy-naive stage IIIB (effusion) or stage IV nonsquamous non–small-cell lung cancer (NSCLC).Patients and MethodsPatients received pemetrexed 500 mg/m2, carboplatin area under the concentration-time curve of 6, and bevacizumab 15 mg/kg every 3 weeks for six cycles. For patients with response or stable disease, pemetrexed and bevacizumab were continued until disease progression or unacceptable toxicity.ResultsFifty patients were enrolled and received treatment. The median follow-up was 13.0 months, and the median number of treatment cycles was seven (range, one to 51). Thirty patients (60%) completed ≥ six treatment cycles, and nine (18%) completed ≥ 18 treatment cycles. Among the 49 patients assessable for response, the objective response rate was 55% (95% CI, 41% to 69%). Median progression-free and overall survival rates were 7.8 months (95% CI, 5.2 to 11.5 months) and 14.1 months (95% CI, 10.8 to 19.6 months), respectively. Grade 3/4 hematologic toxicity was modest—anemia (6%; 0), neutropenia (4%; 0), and thrombocytopenia (0; 8%). Grade 3/4 nonhematologic toxicities were proteinuria (2%; 0), venous thrombosis (4%; 2%), arterial thrombosis (2%; 0), fatigue (8%; 0), infection (8%; 2%), nephrotoxicity (2%; 0), and diverticulitis (6%; 2%). There were no grade 3 or greater hemorrhagic events or hypertension cases.ConclusionThis regimen, involving a maintenance component, was associated with acceptable toxicity and relatively long survival in patients with advanced nonsquamous NSCLC. These results justify a phase III comparison against the standard-of-care in this patient population.

Amifostine, cisplatin, and vinblastine in metastatic non-small-cell lung cancer: a report of high response rates and prolonged survival.

1996 ◽  
Vol 14 (6) ◽  
pp. 1913-1921 ◽  
Author(s):  
J H Schiller ◽  
B Storer ◽  
J Berlin ◽  
J Wittenkeller ◽  
M Larson ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Performance Status ◽  
Objective Response ◽  
Small Cell ◽  
Small Cell Lung ◽  
Computed Tomographic ◽  
Metastatic Nsclc ◽  
Grade 3

PURPOSE Based on preclinical and clinical studies that suggested amifostine may potentiate the effects of cytotoxic drugs, we conducted a phase II trial of amifostine, cisplatin, and vinblastine (ACV) in patients with metastatic non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Twenty-five patients with metastatic NSCLC received amifostine (740 or 910 mg/m2) before 120 mg/m2 of cisplatin on day 1, plus weekly 5 mg/m2 of vinblastine without amifostine. Cycles were repeated every 4 weeks. Patients were required to have good performance status, no prior chemotherapy or biologic therapy, adequate organ function, and measurable disease. RESULTS Sixteen of 25 assessable patients had an objective response documented by computed tomographic (CT) scan (64%; 95% confidence interval, 45% to 85%). With a median duration of follow-up of 19.2 months, the estimated median survival is 17 months and 1-year survival is 64% (+/- 10%). Toxicities included grades 3 and 4 neutropenia (8% and 92%, respectively) and nausea and vomiting (32% and 4%, respectively). Reversible grade 3 nephrotoxicity occurred in 12% of patients, although only one of 13 patients (7%) who received > or = four cycles of therapy had > or = 40% reduction in creatinine clearance. Grade 3 neuropathy was observed in seven patients at cumulative cisplatin doses that ranged from 324 to 660 mg/m2; grade 3 ototoxicity occurred in three patients at cumulative cisplatin doses that ranged from 390 to 450 mg/m2. Four patients (16%) required early stopping of an amifostine infusion due to hypotension. CONCLUSION ACV appears to be a highly active regimen in metastatic NSCLC. Acute toxicities were generally reversible and the data suggest that amifostine may protect against long-term renal insufficiency from cumulative doses of cisplatin. Although the sample size of this trial is small, the results are significantly encouraging to warrant confirmation in randomized multiinstitutional trials.

Bortezomib ± docetaxel in previously treated patients with advanced non-small cell lung cancer (NSCLC): A phase 2 study

2005 ◽  
Vol 23 (16_suppl) ◽  
pp. 7034-7034 ◽  
Author(s):  
M. P. Fanucchi ◽  
F. Fossella ◽  
P. Fidias ◽  
R. B. Natale ◽  
R. J. Belt ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Phase 2 ◽  
Small Cell Lung ◽  
Phase 2 Study ◽  
Previously Treated Patients ◽  
Previously Treated

scholarly journals Phase 2 Study of the HSP-90 Inhibitor AUY922 in Previously Treated and Molecularly Defined Patients with Advanced Non–Small Cell Lung Cancer

2018 ◽  
Vol 13 (4) ◽  
pp. 576-584 ◽  
Author(s):  
Enriqueta Felip ◽  
Fabrice Barlesi ◽  
Benjamin Besse ◽  
Quincy Chu ◽  
Leena Gandhi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Phase 2 ◽  
Small Cell Lung ◽  
Phase 2 Study ◽  
Previously Treated ◽  
Hsp 90

Randomized Phase III Trial of Paclitaxel Plus Carboplatin Versus Vinorelbine Plus Cisplatin in the Treatment of Patients With Advanced Non–Small-Cell Lung Cancer: A Southwest Oncology Group Trial

2001 ◽  
Vol 19 (13) ◽  
pp. 3210-3218 ◽  
Author(s):  
Karen Kelly ◽  
John Crowley ◽  
Paul A. Bunn ◽  
Cary A. Presant ◽  
Patra K. Grevstad ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Resource Utilization ◽  
Cell Lung Cancer ◽  
Objective Response ◽  
Survival Rates ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Grade 3

PURPOSE: This randomized trial was designed to determine whether paclitaxel plus carboplatin (PC) offered a survival advantage over vinorelbine plus cisplatin (VC) for patients with advanced non–small-cell lung cancer. Secondary objectives were to compare toxicity, tolerability, quality of life (QOL), and resource utilization. PATIENTS AND METHODS: Two hundred two patients received VC (vinorelbine 25 mg/m2/wk and cisplatin 100 mg/m2/d, day 1 every 28 days) and 206 patients received PC (paclitaxel 225 mg/m2 over 3 hours with carboplatin area under the curve of 6, day 1 every 21 days). Patients completed QOL questionnaires at baseline, 13 weeks, and 25 weeks. Resource utilization forms were completed at five time points through 24 months. RESULTS: Patient characteristics were similar between the groups. The objective response rate was 28% in the VC arm and 25% in the PC arm. Median survival was 8 months in both arms, with 1-year survival rates of 36% and 38%, respectively. Grade 3 and 4 leukopenia (P = .002) and neutropenia (P = .008) occurred more frequently on the VC arm. Grade 3 nausea and vomiting were higher on the VC arm (P = .001, P = .007), and grade 3 peripheral neuropathy was higher on the PC arm (P < .001). More patients on the VC arm discontinued therapy because of toxicity (P = .001). No difference in QOL was observed. Overall costs on the PC arm were higher than on the VC arm because of drug costs. CONCLUSION: PC is equally efficacious as VC for the treatment of advanced non–small-cell lung cancer. PC is less toxic and better tolerated but more expensive than VC. New treatment strategies should be pursued.

scholarly journals Phase II trial of S-1 plus cisplatin combined with bevacizumab for advanced non-squamous non-small cell lung cancer (TCOG LC-1202)

2019 ◽  
Vol 49 (8) ◽  
pp. 749-754
Author(s):  
Akihiko Miyanaga ◽  
Kaoru Kubota ◽  
Yukio Hosomi ◽  
Yusuke Okuma ◽  
Koichi Minato ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Primary Endpoint ◽  
Objective Response ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Standard Chemotherapy Regimen ◽  
Grade 3

Abstract Background S-1 plus cisplatin is a standard chemotherapy regimen for advanced non-small cell lung cancer (NSCLC). The addition of bevacizumab has been shown to significantly improve overall survival (OS) in patients with advanced non-squamous (NSq) NSCLC who received carboplatin plus paclitaxel, however, failed to show an OS advantage in patients who received cisplatin plus gemcitabine. Methods Chemotherapy-naive patients with Stage IIIB, IV or recurrent non-SQ NSCLC were treated with a 3-week cycle of S-1 80 mg/m2 on days 1–14, cisplatin 60 mg/m2 on day 8 and bevacizumab 15 mg/kg on day 8 for 4–6 cycles. Patients without progressive disease (PD) received maintenance bevacizumab 15 mg/kg on day 1 with a 3-week cycle and S-1 80 mg/m2 every other day. The primary endpoint was progression-free survival (PFS). Secondary endpoints were objective response rate (ORR), OS, toxicity profile and Quality of life (QOL). Results From June 2013 to January 2015, 39 eligible patients were enrolled from eight institutions. Thirty-one patients (79%) completed four cycles of induction chemotherapy, and maintenance chemotherapy was initiated in 23 patients (59%). Median PFS, OS and ORR were 7.3 months (95% CI: 5.9–8.7), 21.4 months (95% CI: 14.7—not reached) and 64%, respectively. The most common grade 3/4 toxicities were leukopenia (12.8%), neutropenia (23.0%) and hypertension (28.2%). QOL analyses showed detrimental effects after initiation of the regimen. Conclusions S-1 plus cisplatin in combination with bevacizumab met the primary endpoint in patients with advanced NSq-NSCLC. RR was anticipated to be high with acceptable toxicities.

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