RT Journal Article
T1 Randomized Phase II Study of Paclitaxel plus Alisertib versus Paclitaxel plus Placebo as Second-Line Therapy for SCLC: Primary and Correlative Biomarker Analyses.
A1 Owonikoko, Taofeek K
A1 Niu, Huifeng
A1 Nackaerts, Kristiaan
A1 Csoszi, Tibor
A1 Ostoros, Gyula
A1 Mark, Zsuzsanna
A1 Baik, Christina
A1 Joy, Anil Abraham
A1 Chouaid, Christos
A1 Jaime, Jesus Corral
A1 Kolek, Vitezslav
A1 Majem, Margarita
A1 Roubec, Jaromir
A1 Santos, Edgardo S
A1 Chiang, Anne C
A1 Speranza, Giovanna
A1 Belani, Chandra P
A1 Chiappori, Alberto
A1 Patel, Manish R
A1 Czebe, Krisztina
A1 Byers, Lauren
A1 Bahamon, Brittany
A1 Li, Cong
A1 Sheldon-Waniga, Emily
A1 Kong, Eric F
A1 Williams, Miguel
A1 Badola, Sunita
A1 Shin, Hyunjin
A1 Bedford, Lisa
A1 Ecsedy, Jeffrey A
A1 Bryant, Matthew
A1 Jones, Sian
A1 Simmons, John
A1 Leonard, E Jane
A1 Ullmann, Claudio Dansky
A1 Spigel, David R
A1 C14018 study investigators, 
K1 Alisertib
K1 Aurora A kinase
K1 Paclitaxel
K1 Phase II
K1 SCLC
AB We assessed the Aurora A kinase inhibitor, alisertib, plus paclitaxel (henceforth referred to as alisertib/paclitaxel) as second-line treatment for SCLC. In this double-blind study, patients with relapsed or refractory SCLC were stratified by relapse type (sensitive versus resistant or refractory) and brain metastases and randomized 1:1 to alisertib/paclitaxel or placebo plus paclitaxel (henceforth referred to as placebo/paclitaxel) in 28-day cycles. The primary end point was progression-free survival (PFS). Associations of c-Myc expression in tumor tissue (prespecified) and genetic alterations in circulating tumor DNA (retrospective) with clinical outcome were evaluated. A total of 178 patients were enrolled (89 in each arm). The median PFS was 3.32 months with alisertib/paclitaxel versus 2.17 months with placebo/paclitaxel (hazard ratio [HR] = 0.77, 95% confidence limit [CI]: 0.557-1.067, p = 0.113 in the intent-to-treat population versus HR = 0.71, 95% CI: 0.509-0.985, p = 0.038 with corrected analysis applied). Among 140 patients with genetic alternations, patients with cell cycle regulator mutations (cyclin-dependent kinase 6 gene [CDK6], retinoblastoma-like 1 gene [RBL1], retinoblastoma-like 2 gene [RBL2], and retinoblastoma 1 gene [RB1]) had significantly improved PFS with alisertib/paclitaxel versus with placebo/paclitaxel (3.68 versus 1.80 months, respectively [HR = 0.395, 95% CI: 0.239-0.654, p = 0.0003]), and overall survival (7.20 versus 4.47 months, respectively [HR = 0.427, 95% CI: 0.259-0.704, p = 0.00085]). A subset of patients with c-Myc expression showed significantly improved PFS with alisertib/paclitaxel. The incidence of grade 3 or higher drug-related adverse events was 67% (58 patients) with alisertib/paclitaxel versus 22% (25 patients) with placebo/paclitaxel. Twelve patients (14%) versus 11 (12%) died on study, including four versus zero treatment-related deaths. Efficacy signals were seen with alisertib/paclitaxel in relapsed or refractory SCLC. c-Myc expression and mutations in cell cycle regulators may be potential predictive biomarkers of alisertib efficacy; further prospective validations are warranted.
YR 2019
FD 2019-10-23
LK http://hdl.handle.net/10668/15444
UL http://hdl.handle.net/10668/15444
LA en
DS RISalud
RD Apr 7, 2025