2024-03-28T13:25:46Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/74242021-11-29T21:27:20Zcom_20.500.12105_2174com_20.500.12105_2051com_20.500.12105_2173col_20.500.12105_2175
00925njm 22002777a 4500
dc
Socinski, Mark A
author
Kaye, Frederic J
author
Spigel, David R
author
Kudrik, Fred J
author
Ponce, Santiago
author
Ellis, Peter M
author
Majem, Margarita
author
Lorigan, Paul
author
Gandhi, Leena
author
Gutierrez, Martin E
author
Nepert, Dale
author
Corral, Jesus
author
Paz Ares, Luis Gonzaga
author
2017-01-18
INTRODUCTION: This trial assessed the safety and efficacy of LM in combination with carboplatin/etoposide therapy compared to carboplatin/etoposide treatment alone in patients with previously untreated extensive-disease small-cell lung cancer (ED-SCLC). PATIENTS AND METHODS: A run-in phase 1 stage was used to determine the recommended phase 2 dose and characterize the dose-limiting toxicities of LM in combination with carboplatin/etoposide followed by LM alone in patients with CD56-positive solid tumors. In phase 2, chemotherapy-naive ED-SCLC patients were randomized 2:1 to carboplatin AUC (area under the plasma concentration vs. time curve) of 5 day 1 + etoposide 100 mg/m2 days 1 to 3 plus LM (arm 1) or alone (arm 2). RESULTS: In the phase 1 study (n = 33), a dose of LM at 112 mg/m2 with carboplatin/etoposide was identified as the recommended phase 2 dose. However, because of an increased incidence of peripheral neuropathy events during early phase 2, this dose was reduced to 90 mg/m2. In phase 2, a total of 94 and 47 evaluable patients were assigned to arms 1 and 2, respectively. No difference in median progression-free survival was observed between arms 1 and 2 (6.2 vs. 6.7 months). The most common treatment-emergent adverse event leading to discontinuation was peripheral neuropathy (29%). A total of 21 patients had a treatment-emergent adverse event leading to death (18 in arm 1 and 3 in arm 2); for 10 individuals, this was an infection (pneumonia or sepsis) deemed to be related to the study drug. CONCLUSION: The combination of LM plus carboplatin/etoposide did not improve efficacy over standard carboplatin/etoposide doublet therapy in ED-SCLC patients and showed increased toxicity, including a higher incidence of serious infections with fatal outcomes.
Clin Lung Cancer. 2017;18(1):68-76
15257304
http://hdl.handle.net/20.500.12105/7424
28341109
10.1016/j.cllc.2016.09.002
1938-0690
Clinical lung cancer
Clinical trial
Combination therapy
SCLC
Targeted drug delivery
Tolerability
Phase 1/2 Study of the CD56-Targeting Antibody-Drug Conjugate Lorvotuzumab Mertansine (IMGN901) in Combination With Carboplatin/Etoposide in Small-Cell Lung Cancer Patients With Extensive-Stage Disease