Randomized phase II study of dulanermin in combination with paclitaxel, carboplatin, and bevacizumab in advanced non-small-cell lung cancer.

Abstract

PURPOSE:

To evaluate the efficacy and safety of dulanermin combined with paclitaxel and carboplatin (PC) and bevacizumab (PCB) as first-line treatment for advanced or recurrent non-small-cell lung cancer (NSCLC).

PATIENTS AND METHODS:

Patients with squamous NSCLC and/or CNS metastases received PC every 3 weeks alone (arm 1) or with dulanermin 8 mg/kg for 5 days (arm 2). Patients with nonsquamous NSCLC received PCB alone (arm 3) or with dulanermin 8 mg/kg for 5 days (arm 4) or 20 mg/kg for 2 days (arm 5). The primary end point was the objective response rate (ORR).

RESULTS:

Overall, 213 patients were randomly assigned (arm 1, n = 41; arm 2, n = 39; arm 3, n = 42; arm 4, n = 40; arm 5, n = 41). The ORR in arms 1 to 5 was 39% (95% CI, 24% to 56%), 38% (95% CI, 24% to 54%), 50% (95% CI, 35% to 65%), 40% (95% CI, 25% to 56%), and 40% (95% CI, 25% to 56%), respectively. The odds ratio for ORR was 1.04 (P = 1.000) for arm 1 versus arm 2, 1.53 (P = .391) for arm 3 and versus arm 4, and 1.53 (P = .391) for arm 3 versus arm 5. The most common grade ≥ 3 adverse events were neutropenia, asthenia, anemia, thrombocytopenia, and hemoptysis. Of 161 available serum samples, a trend toward increased caspase-cleaved cytokeratin-18 was observed after dulanermin treatment in cycles 1 and 2. Among 84 patients evaluated for GalNT14 expression, there was a trend toward favorable progression-free survival and overall survival with dulanermin treatment in those with high GalNT14 expression.

CONCLUSION:

The addition of dulanermin to PC and PCB did not improve outcomes in unselected patients with previously untreated advanced or recurrent NSCLC.

• Authors: Jean-Charles Soria, Zsuzsanna Márk, Petr Zatloukal, Barna Szima, István Albert, Erzsébet Juhász, Jean-Louis Pujol, Jerzy Kozielski, Nigel Baker, Dominic Smethurst, Yong-jiang Hei, Avi Ashkenazi, Howard Stern, Lukas Amler, Yang Pan, Fiona Blackhall
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 29 Issue 33 Pg. 4442-51 (Nov 20 2011) ISSN: 1527-7755 [Electronic] United States
• PMID: 22010015 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal, Humanized
• Keratin-18
• TNF-Related Apoptosis-Inducing Ligand
• TNFSF10 protein, human
• Bevacizumab
• Carboplatin
• N-Acetylgalactosaminyltransferases
• polypeptide N-acetylgalactosaminyltransferase
• Paclitaxel

Topics

• Adult
• Aged
• Antibodies, Monoclonal, Humanized (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Bevacizumab
• Carboplatin (administration & dosage)
• Carcinoma, Non-Small-Cell Lung (drug therapy, mortality)
• Female
• Humans
• Keratin-18 (blood)
• Lung Neoplasms (drug therapy, mortality)
• Male
• Middle Aged
• N-Acetylgalactosaminyltransferases (analysis)
• Paclitaxel (administration & dosage)
• TNF-Related Apoptosis-Inducing Ligand (administration & dosage)