Motesanib plus carboplatin/paclitaxel in patients with advanced squamous non-small-cell lung cancer: results from the randomized controlled MONET1 study.

Abstract

INTRODUCTION:

The phase 3 MONET1 study evaluated motesanib (a small-molecule inhibitor of vascular endothelial growth factor receptors) plus carboplatin/paclitaxel versus placebo plus carboplatin/paclitaxel as first-line therapy for advanced non-small-cell lung cancer (NSCLC). Treatment and enrollment of patients with squamous histology were permanently discontinued following higher early mortality and gross hemoptysis in those with squamous NSCLC who received motesanib. Enrollment of patients with nonsquamous histology was temporarily halted, but resumed following a protocol amendment (Scagliotti et al. J Clin Oncol. 2012;30:2829-2836). Herein, we report data from the squamous cohort.

METHODS:

Patients with stage IIIB/IV or recurrent squamous NSCLC (without prior systemic therapy for advanced disease) received up to six 3-week cycles of chemotherapy (carboplatin, area under the curve 6 mg/mL•min/paclitaxel, 200 mg/m) and were randomized 1:1 to receive motesanib 125 mg (Arm A) or placebo (Arm B) once daily. The primary end point was overall survival.

RESULTS:

Three-hundred and sixty patients with squamous NSCLC were randomized (Arm A, n = 182; Arm B, n = 178) between July 2007 and November 2008. Twenty-three patients (13%) in Arm A and 10 (6%) in Arm B had fatal adverse events within the first 60 days of treatment. Among these, six patients in Arm A, but none in Arm B, had fatal bleeding events. At final analysis, serious adverse events had occurred in 47% of patients in Arm A and 29% of patients in Arm B. Median overall survival was similar in Arms A and B (11.1 versus 10.7 months).

CONCLUSIONS:

Motesanib plus carboplatin/paclitaxel had unacceptable toxicity compared with carboplatin/paclitaxel alone in patients with advanced squamous NSCLC.

• Authors: Silvia Novello, Giorgio V Scagliotti, Oleksandr Sydorenko, Ihor Vynnychenko, Constantin Volovat, Claus-Peter Schneider, Fiona Blackhall, Sheryl McCoy, Yong-Jiang Hei, David R Spigel
• Journal: Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer (J Thorac Oncol) Vol. 9 Issue 8 Pg. 1154-61 (Aug 2014) ISSN: 1556-1380 [Electronic] United States
• PMID: 25157768 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (adverse effects)
• Carboplatin (administration & dosage)
• Carcinoma, Non-Small-Cell Lung (drug therapy, pathology)
• Carcinoma, Squamous Cell (drug therapy, pathology)
• Disease-Free Survival
• Double-Blind Method
• Early Termination of Clinical Trials
• Female
• Hemoptysis (chemically induced)
• Humans
• Indoles (administration & dosage, adverse effects)
• Lung Neoplasms (drug therapy, pathology)
• Male
• Middle Aged
• Niacinamide (administration & dosage, adverse effects, analogs & derivatives)
• Oligonucleotides
• Paclitaxel (administration & dosage)
• Survival Rate