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Clin Lung Cancer. 2014 May;15(3):188-196.e2. doi: 10.1016/j.cllc.2013.12.005. Epub 2013 Dec 27.

Phase II trial of mapatumumab, a fully human agonist monoclonal antibody to tumor necrosis factor-related apoptosis-inducing ligand receptor 1 (TRAIL-R1), in combination with paclitaxel and carboplatin in patients with advanced non-small-cell lung cancer.

Author information

1
Department of Oncology, Asklepios-Fachkliniken München-Gauting, Munich, Germany. Electronic address: j.pawel@asklepios.com.
2
Alabama Oncology, Birmingham, AL.
3
Tennessee Oncology, Sarah Cannon Research Institute, Nashville, TN.
4
Department of Medical Oncology, Institute of Oncology "Prof. Dr. Alexandru Trestioreanu", Bucharest, Romania.
5
Department of Thoracic Oncology, Hospital Grosshansdorf, Grosshansdorf, Germany.
6
Department of Radiotherapy I-Medical Oncology, Prof Dr Ion Chircuta Institute of Oncology, Cluj, Romania.
7
Preclinical Research, Rockville, MD.
8
Department of Biostatistics, Rockville, MD.
9
Clinical Research, Human Genome Sciences, Rockville, MD.
10
Division of Medical Oncology, Department of Medicine, University of Colorado, Aurora, CO.

Abstract

BACKGROUND:

This phase II study examined the efficacy of mapatumumab in combination with paclitaxel and carboplatin in patients with non-small-cell lung cancer (NSCLC).

PATIENTS AND METHODS:

Patients with stage IIIB or stage IV advanced primary NSCLC were randomly assigned (1:1:1) to receive up to 6 courses of standard-dose paclitaxel and carboplatin or a combination of paclitaxel, carboplatin, and mapatumumab (10 mg/kg or 30 mg/kg). Primary efficacy end points were overall response rate and median progression-free survival (PFS). Secondary efficacy end points included disease control rate, overall survival (OS), time to response, and duration of response. Exploratory studies included evaluation of historical biopsy materials for TRAIL-R1 expression by immunohistochemical analysis and serum levels of M30, a marker of apoptosis, before and after the first 2 doses of mapatumumab. Safety parameters, including adverse events (AEs), laboratory tests, and immunogenicity, were assessed.

RESULTS:

The majority of patients had stage IV disease (79%) and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 (58%); baseline characteristics were similar across treatment arms. No improvements in response or disease control rates, PFS, or OS were gained from the addition of mapatumumab. Adverse events in the mapatumumab arms were generally consistent with toxicities seen in the carboplatin and paclitaxel control arm. Levels of M30 were highly variable, and consistent patterns were not seen across treatment arms.

CONCLUSION:

This study showed no clinical benefit from adding mapatumumab to carboplatin and paclitaxel in unselected patients with NSCLC. The combination was generally well tolerated. The possibility of subgroups sensitive to mapatumumab is discussed.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00583830.

KEYWORDS:

Carboplatin/paclitaxel combination; Death receptors; Targeted biological agent

PMID:
24560012
DOI:
10.1016/j.cllc.2013.12.005
[Indexed for MEDLINE]
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