Phase III, randomized, placebo-controlled, double-blind trial of motesanib (AMG-706) in combination with paclitaxel and carboplatin in east asian patients with advanced nonsquamous non-small-cell lung cancer
Journal
Journal of Clinical Oncology
Journal Volume
35
Journal Issue
32
Pages
3662-3670
Date Issued
2017
Author(s)
Kubota K
Asato T
Hara K
Yoshioka H
Oshita F
Hida T
Yoh K
Nakagawa K
Hayashi H
Kaneda H
Kato T
Yamada K
Ichinose Y
Tanaka H
Park K
Cho E.K
Lee K.-H
Lin C.-B
Abstract
Purpose This phase III, randomized, placebo-controlled, double-blind study determined whether motesanib improved progression-free survival (PFS) compared with placebo in combination with paclitaxel and carboplatin (P/C) in East Asian patients with stage IV/recurrent nonsquamous non-small-cell lung cancer. Patients and Methods Patients were randomly assigned (1:1) to receive oral motesanib 125 mg or placebo once daily plus paclitaxel 200 mg/m2 IV and carboplatin area under the concentration-time curve 6 mg/mL $ min IV for up to six 3-week cycles. Random assignment was stratified by epidermal growth factor receptor status, region, and weight loss in the 6 months before assignment. The primary end point was PFS, the key secondary end point was overall survival, and other secondary end points were objective response rate, time to tumor response, duration of response, and adverse events (AEs). Results Four hundred one patients were assigned to receive motesanib plus P/C (n = 197) or placebo plus P/C (n = 204).Median PFS was 6.1 v 5.6months formotesanib versus placebo (stratified log-rank test P = .0825; stratified hazard ratio, 0.81; 95%CI, 0.64 to 1.03; P = .0820);median overall survivalwas not reached versus 21.6 months (P = .5514). In secondary analyses, the objective response rate was 60.1%v 41.6% (P < .001); median time to tumor response, 1.4 v 1.6months, and median duration of response, 5.3 v 4.1 months. Incidence of grade ? 3 AEs (86.7% v 67.6%) and AEs that led to drug discontinuation (32.7% v 14.2%) were higher with motesanib than with placebo. AEs reported more frequently with motesanib were GI disorders, hypertension, and gallbladder related. Conclusion Motesanib plus P/C did not significantly improve PFS versus placebo plus P/C in East Asian patients with stage IV/recurrent nonsquamous non-small-cell lung cancer. ? 2017 by American Society of Clinical Oncology.
SDGs
Other Subjects
carboplatin; epidermal growth factor receptor; motesanib; paclitaxel; placebo; antineoplastic agent; carboplatin; imetelstat; indole derivative; nicotinamide; paclitaxel; abdominal pain; adult; advanced cancer; aged; alopecia; anemia; Article; body weight disorder; cancer combination chemotherapy; cancer patient; cancer staging; cancer survival; cholecystitis; controlled study; decreased appetite; diarrhea; double blind procedure; drug efficacy; drug safety; drug withdrawal; dysgeusia; dyspepsia; East Asian; epistaxis; female; gallbladder disease; gastrointestinal disease; human; hypertension; large cell carcinoma; leukocyte count; leukopenia; lung adenocarcinoma; major clinical study; male; monotherapy; multicenter study; multiple cycle treatment; myalgia; nausea; neutrophil count; non small cell lung cancer; overall survival; phase 3 clinical trial; pneumonia; priority journal; progression free survival; proteinuria; randomized controlled trial; side effect; thrombocyte count; thrombocytopenia; treatment response; vomiting; weight reduction; analogs and derivatives; Carcinoma, Non-Small-Cell Lung; clinical trial; ethnology; Hong Kong; Japan; Lung Neoplasms; middle aged; pathology; phase 2 clinical trial; South Korea; survival rate; treatment outcome; tumor recurrence; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Double-Blind Method; Female; Hong Kong; Humans; Indoles; Japan; Lung Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Niacinamide; Paclitaxel; Republic of Korea; Survival Rate; Treatment Outcome
Publisher
American Society of Clinical Oncology
Type
journal article