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.

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 5.6 months for motesanib versus placebo (stratified log-rank test P = .0825; stratified hazard ratio, 0.81; 95% CI, 0.64 to 1.03; P = .0820); median overall survival was 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 1.6 months, 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.

• Authors: Kaoru Kubota, Hiroshige Yoshioka, Fumihiro Oshita, Toyoaki Hida, Kiyotaka Yoh, Hidetoshi Hayashi, Terufumi Kato, Hiroyasu Kaneda, Kazuhiko Yamada, Hiroshi Tanaka, Yukito Ichinose, Keunchil Park, Eun Kyung Cho, Kyung-Hee Lee, Chih-Bin Lin, James Chih-Hsin Yang, Kaori Hara, Takayuki Asato, Kazuhiko Nakagawa
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 35 Issue 32 Pg. 3662-3670 (Nov 10 2017) ISSN: 1527-7755 [Electronic] United States
• PMID: 28902534 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• Indoles
• Oligonucleotides
• Niacinamide
• Carboplatin
• imetelstat
• Paclitaxel

Topics

• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Carboplatin (administration & dosage)
• Carcinoma, Non-Small-Cell Lung (drug therapy, ethnology, pathology)
• Double-Blind Method
• Female
• Hong Kong
• Humans
• Indoles (administration & dosage)
• Japan
• Lung Neoplasms (drug therapy, ethnology, pathology)
• Male
• Middle Aged
• Neoplasm Recurrence, Local (drug therapy)
• Neoplasm Staging
• Niacinamide (administration & dosage, analogs & derivatives)
• Oligonucleotides
• Paclitaxel (administration & dosage)
• Republic of Korea
• Survival Rate
• Treatment Outcome