title: Randomized phase 2 study of the cyclin-dependent kinase inhibitor dinaciclib (MK-7965) versus erlotinib in patients with non-small cell lung cancer.
abstract: 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.
  
  
  
  The study was comprised of 2 parts: in part 1, patients were randomized to either intravenous (IV) dinaciclib (50 mg/m2) or oral erlotinib (150 mg) 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.
  
  
  
  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.
  
  
  
  Dinaciclib, administered IV, was well tolerated at the 50 mg/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.
authors.affiliation: Institute for Translational Oncology Research, 900 West Faris Road, 3rd Floor, Greenville, SC 29605, USA.
authors.forename: Joe J
authors.initials: JJ
authors.lastname: Stephenson
authors.affiliation: Mary Crowley Cancer Research Centers, 1700 Pacific Avenue, Dallas, TX 75201, USA.
authors.forename: John
authors.initials: J
authors.lastname: Nemunaitis
authors.affiliation: Cross Cancer Institute, University of Alberta, 11560 University Avenue NW, Edmonton, AB T6G 1Z2, Canada.
authors.forename: Anil A
authors.initials: AA
authors.lastname: Joy
authors.affiliation: Institute for Translational Oncology Research, 900 West Faris Road, 3rd Floor, Greenville, SC 29605, USA.
authors.forename: Julie C
authors.initials: JC
authors.lastname: Martin
authors.affiliation: Merck & Co., Inc., 1 Merck Drive, Whitehouse Station, NJ 08889, USA.
authors.forename: Ying-Ming
authors.initials: YM
authors.lastname: Jou
authors.affiliation: Merck & Co., Inc., 1 Merck Drive, Whitehouse Station, NJ 08889, USA.
authors.forename: Da
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Merck & Co., Inc., 1 Merck Drive, Whitehouse Station, NJ 08889, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Statkevich
authors.affiliation: Merck & Co., Inc., 1 Merck Drive, Whitehouse Station, NJ 08889, USA.
authors.forename: Siu-Long
authors.initials: SL
authors.lastname: Yao
authors.affiliation: Merck & Co., Inc., 1 Merck Drive, Whitehouse Station, NJ 08889, USA.
authors.forename: Yali
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Merck & Co., Inc., 1 Merck Drive, Whitehouse Station, NJ 08889, USA.
authors.forename: Honghong
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Merck & Co., Inc., 1 Merck Drive, Whitehouse Station, NJ 08889, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Small
authors.affiliation: Merck & Co., Inc., 1 Merck Drive, Whitehouse Station, NJ 08889, USA.
authors.forename: Rajat
authors.initials: R
authors.lastname: Bannerji
authors.affiliation: University of Maryland Greenebaum Cancer Center, 22 South Greene Street, Baltimore, MD 21201, USA. Electronic address: medelman@salud.unm.edu.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Edelman
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D003497:Cyclic N-Oxides; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D000069347:Erlotinib Hydrochloride; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007212:Indolizines; D007275:Injections, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009503:Neutropenia / Q000209:etiology; D011726:Pyridinium Compounds / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D011799:Quinazolines / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D003497:Cyclic N-Oxides; D007212:Indolizines; D011726:Pyridinium Compounds; D011799:Quinazolines; C553669:dinaciclib; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D018844:Cyclin-Dependent Kinases
keywords: CDK inhibitor; Dinaciclib; Erlotinib; Monotherapy; NSCLC; Phase 2