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


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.


CONCLUSIONS
The addition of dulanermin to PC and PCB did not improve outcomes in unselected patients with previously untreated advanced or recurrent NSCLC.
South Paris University, Institut Gustave Roussy, Villejuif, France. soria@igr.fr
Jean-Charles
JC
Soria
Zsuzsanna
Z
Márk
Petr
P
Zatloukal
Barna
B
Szima
István
I
Albert
Erzsébet
E
Juhász
Jean-Louis
JL
Pujol
Jerzy
J
Kozielski
Nigel
N
Baker
Dominic
D
Smethurst
Yong-jiang
YJ
Hei
Avi
A
Ashkenazi
Howard
H
Stern
Lukas
L
Amler
Yang
Y
Pan
Fiona
F
Blackhall
D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D006801:Humans; D053538:Keratin-18 / Q000097:blood; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D017350:N-Acetylgalactosaminyltransferases / Q000032:analysis; D017239:Paclitaxel / Q000008:administration & dosage; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000008:administration & dosage; D000097763:Polypeptide N-acetylgalactosaminyltransferase
D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D016190:Carboplatin; D053538:Keratin-18; D017350:N-Acetylgalactosaminyltransferases; D017239:Paclitaxel; D053221:TNF-Related Apoptosis-Inducing Ligand; D000097763:Polypeptide N-acetylgalactosaminyltransferase; C505653:TNFSF10 protein, human