TY - JOUR
T1 - Randomized phase 2 study of the cyclin-dependent kinase inhibitor dinaciclib (MK-7965) versus erlotinib in patients with non-small cell lung cancer
AU - Stephenson, Joe J.
AU - Nemunaitis, John
AU - Joy, Anil A.
AU - Martin, Julie C.
AU - Jou, Ying Ming
AU - Zhang, Da
AU - Statkevich, Paul
AU - Yao, Siu Long
AU - Zhu, Yali
AU - Zhou, Honghong
AU - Small, Karen
AU - Bannerji, Rajat
AU - Edelman, Martin J.
PY - 2014/2
Y1 - 2014/2
N2 - Objectives: Dinaciclib (MK-7965, formerly SCH 727965), a novel, small-molecule inhibitor of cyclin-dependent kinases, has been shown to induce apoptosis in preclinical studies of human tumor cell lines, including non-small cell lung cancer (NSCLC) cells. Erlotinib, an epidermal growth factor receptor inhibitor, is approved for the treatment of advanced NSCLC as second- or third-line therapy. This phase 2, randomized, multicenter, open-label study compared dinaciclib with erlotinib in patients with previously treated NSCLC. Materials and methods: The study was comprised of 2 parts: in part 1, patients were randomized to either intravenous (IV) dinaciclib (50mg/m2) or oral erlotinib (150mg) using an adaptive Bayesian design that adjusted the randomization ratio in favor of the more active arm, and in part 2, patients who had progressed on erlotinib were permitted to cross over to receive dinaciclib at the same dosage as in part 1. Patients were followed until disease progression or death, initiation of nonstudy cancer treatment, discontinuation, or withdrawal of consent. The primary efficacy end point was time-to-progression (TTP) in part 1 and objective response rate (ORR) in part 2. Results: Based on Kaplan-Meier estimates, the median TTP was 1.49 months (95% confidence interval [CI]: 1.31, 2.63) following initial treatment with dinaciclib, compared with 1.58 months (95% CI: 1.38, 2.83) with erlotinib. No objective responses were observed following initial treatment with dinaciclib. Common severe (grade 3 or 4) drug-related adverse effects included neutropenia, leukopenia, vomiting, and diarrhea. Conclusions: Dinaciclib, administered IV, was well tolerated at the 50mg/m2 dose, but does not have activity as monotherapy in previously treated NSCLC. Evaluation of dinaciclib in combination with other agents for other indications including breast cancer and multiple myeloma is in progress.
AB - Objectives: Dinaciclib (MK-7965, formerly SCH 727965), a novel, small-molecule inhibitor of cyclin-dependent kinases, has been shown to induce apoptosis in preclinical studies of human tumor cell lines, including non-small cell lung cancer (NSCLC) cells. Erlotinib, an epidermal growth factor receptor inhibitor, is approved for the treatment of advanced NSCLC as second- or third-line therapy. This phase 2, randomized, multicenter, open-label study compared dinaciclib with erlotinib in patients with previously treated NSCLC. Materials and methods: The study was comprised of 2 parts: in part 1, patients were randomized to either intravenous (IV) dinaciclib (50mg/m2) or oral erlotinib (150mg) using an adaptive Bayesian design that adjusted the randomization ratio in favor of the more active arm, and in part 2, patients who had progressed on erlotinib were permitted to cross over to receive dinaciclib at the same dosage as in part 1. Patients were followed until disease progression or death, initiation of nonstudy cancer treatment, discontinuation, or withdrawal of consent. The primary efficacy end point was time-to-progression (TTP) in part 1 and objective response rate (ORR) in part 2. Results: Based on Kaplan-Meier estimates, the median TTP was 1.49 months (95% confidence interval [CI]: 1.31, 2.63) following initial treatment with dinaciclib, compared with 1.58 months (95% CI: 1.38, 2.83) with erlotinib. No objective responses were observed following initial treatment with dinaciclib. Common severe (grade 3 or 4) drug-related adverse effects included neutropenia, leukopenia, vomiting, and diarrhea. Conclusions: Dinaciclib, administered IV, was well tolerated at the 50mg/m2 dose, but does not have activity as monotherapy in previously treated NSCLC. Evaluation of dinaciclib in combination with other agents for other indications including breast cancer and multiple myeloma is in progress.
KW - CDK inhibitor
KW - Dinaciclib
KW - Erlotinib
KW - Monotherapy
KW - NSCLC
KW - Phase 2
UR - http://www.scopus.com/inward/record.url?scp=84892865722&partnerID=8YFLogxK
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=purepublist2023&SrcAuth=WosAPI&KeyUT=WOS:000331495000015&DestLinkType=FullRecord&DestApp=WOS
U2 - 10.1016/j.lungcan.2013.11.020
DO - 10.1016/j.lungcan.2013.11.020
M3 - Article
C2 - 24388167
SN - 0169-5002
VL - 83
SP - 219
EP - 223
JO - Lung Cancer
JF - Lung Cancer
IS - 2
ER -
