PMID- 31504118
OWN - NLM
STAT- MEDLINE
DCOM- 20200731
LR  - 20240229
IS  - 1569-8041 (Electronic)
IS  - 0923-7534 (Print)
IS  - 0923-7534 (Linking)
VI  - 30
IP  - 10
DP  - 2019 Oct 1
TI  - Myelopreservation with the CDK4/6 inhibitor trilaciclib in patients with 
      small-cell lung cancer receiving first-line chemotherapy: a phase Ib/randomized 
      phase II trial.
PG  - 1613-1621
LID - S0923-7534(19)60981-6 [pii]
LID - 10.1093/annonc/mdz278 [doi]
AB  - BACKGROUND: Chemotherapy-induced damage of hematopoietic stem and progenitor 
      cells (HSPC) causes multi-lineage myelosuppression. Trilaciclib is an intravenous 
      CDK4/6 inhibitor in development to proactively preserve HSPC and immune system 
      function during chemotherapy (myelopreservation). Preclinically, trilaciclib 
      transiently maintains HSPC in G1 arrest and protects them from chemotherapy 
      damage, leading to faster hematopoietic recovery and enhanced antitumor immunity. 
      PATIENTS AND METHODS: This was a phase Ib (open-label, dose-finding) and phase II 
      (randomized, double-blind placebo-controlled) study of the safety, efficacy and 
      PK of trilaciclib in combination with etoposide/carboplatin (E/P) therapy for 
      treatment-naive extensive-stage small-cell lung cancer patients. Patients 
      received trilaciclib or placebo before E/P on days 1-3 of each cycle. Select end 
      points were prespecified to assess the effect of trilaciclib on myelosuppression 
      and antitumor efficacy. RESULTS: A total of 122 patients were enrolled, with 19 
      patients in part 1 and 75 patients in part 2 receiving study drug. Improvements 
      were seen with trilaciclib in neutrophil, RBC (red blood cell) and lymphocyte 
      measures. Safety on trilaciclib+E/P was improved with fewer >/=G3 adverse events 
      (AEs) in trilaciclib (50%) versus placebo (83.8%), primarily due to less 
      hematological toxicity. No trilaciclib-related >/=G3 AEs occurred. Antitumor 
      efficacy assessment for trilaciclib versus placebo, respectively, showed: ORR 
      (66.7% versus 56.8%, P = 0.3831); median PFS [6.2 versus 5.0 m; hazard ratio (HR) 
      0.71; P = 0.1695]; and OS (10.9 versus 10.6 m; HR 0.87; P = 0.6107). CONCLUSION: 
      Trilaciclib demonstrated an improvement in the patient's tolerability of 
      chemotherapy as shown by myelopreservation across multiple hematopoietic lineages 
      resulting in fewer supportive care interventions and dose reductions, improved 
      safety profile, and no detriment to antitumor efficacy. These data demonstrate 
      strong proof-of-concept for trilaciclib's myelopreservation benefits. CLINICAL 
      TRAIL NUMBER: NCT02499770.
CI  - (c) The Author(s) 2019. Published by Oxford University Press on behalf of the 
      European Society for Medical Oncology.
FAU - Weiss, J M
AU  - Weiss JM
AD  - Division of Hematology and Oncology, Lineberger Comprehensive Cancer Center at 
      the University of North Carolina, Chapel Hill, USA.
FAU - Csoszi, T
AU  - Csoszi T
AD  - Oncology, Hetenyi Geza Korhaz, Onkologiai Kozpont, Szolnok, Hungary.
FAU - Maglakelidze, M
AU  - Maglakelidze M
AD  - Department of Oncology, Research Institute of Clinical Medicine, Tbilisi, 
      Georgia, USA.
FAU - Hoyer, R J
AU  - Hoyer RJ
AD  - Department of Oncology, Memorial Hospital, University of Colorado Health, 
      Colorado Springs, USA.
FAU - Beck, J T
AU  - Beck JT
AD  - Department of Medical Oncology and Hematology, Highlands Oncology Group, 
      Fayetteville, USA.
FAU - Domine Gomez, M
AU  - Domine Gomez M
AD  - Department of Oncology, University Hospital Fundacion Jimenez Diaz, IIS-FJD, 
      Madrid, Spain.
FAU - Lowczak, A
AU  - Lowczak A
AD  - Department of Pulmonology, Faculty of Health and Science, University of Warmia 
      and Mazury in Olsztyn, Poland.
FAU - Aljumaily, R
AU  - Aljumaily R
AD  - Stephenson Cancer Center, University of Oklahoma, Oklahoma City, USA.
FAU - Rocha Lima, C M
AU  - Rocha Lima CM
AD  - Gibbs Cancer Center and Research Institute, Spartanburg, USA.
FAU - Boccia, R V
AU  - Boccia RV
AD  - Center for Cancer and Blood Disorders, Bethesda, USA.
FAU - Hanna, W
AU  - Hanna W
AD  - Hematology/Oncology, University of Tennessee Medical Center, Knoxville, USA.
FAU - Nikolinakos, P
AU  - Nikolinakos P
AD  - University Cancer & Blood Center, LLC, Athens, Greece.
FAU - Chiu, V K
AU  - Chiu VK
AD  - Department of Hematology/Oncology, University of New Mexico Comprehensive Cancer 
      Center, Albuquerque, USA.
FAU - Owonikoko, T K
AU  - Owonikoko TK
AD  - Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory 
      University, Atlanta, USA.
FAU - Schuster, S R
AU  - Schuster SR
AD  - University of Colorado, Fort Collins, USA.
FAU - Hussein, M A
AU  - Hussein MA
AD  - Department of Oncology, Florida Cancer Specialists, Leesburg, USA.
FAU - Richards, D A
AU  - Richards DA
AD  - Department of Oncology, US Oncology Research, Tyler, USA.
FAU - Sawrycki, P
AU  - Sawrycki P
AD  - Department of Cancer Chemotherapy, Provincial Hospital, Torun, Poland.
FAU - Bulat, I
AU  - Bulat I
AD  - ARENSIA Oncology Unit, Institute of Oncology, Chisinau, Moldova.
FAU - Hamm, J T
AU  - Hamm JT
AD  - Department of Medical Oncology, Norton Health Care, Louisville, USA.
FAU - Hart, L L
AU  - Hart LL
AD  - Drug Development Program, Floridia Cancer Specialists, Fort Myers, USA.
FAU - Adler, S
AU  - Adler S
AD  - Clinical Research, G1 Therapeutics, Inc., Research Triangle Park, USA.
FAU - Antal, J M
AU  - Antal JM
AD  - Clinical Research, G1 Therapeutics, Inc., Research Triangle Park, USA.
FAU - Lai, A Y
AU  - Lai AY
AD  - Clinical Research, G1 Therapeutics, Inc., Research Triangle Park, USA.
FAU - Sorrentino, J A
AU  - Sorrentino JA
AD  - Clinical Research, G1 Therapeutics, Inc., Research Triangle Park, USA.
FAU - Yang, Z
AU  - Yang Z
AD  - Clinical Research, G1 Therapeutics, Inc., Research Triangle Park, USA.
FAU - Malik, R K
AU  - Malik RK
AD  - Clinical Research, G1 Therapeutics, Inc., Research Triangle Park, USA.
FAU - Morris, S R
AU  - Morris SR
AD  - Clinical Research, G1 Therapeutics, Inc., Research Triangle Park, USA.
FAU - Roberts, P J
AU  - Roberts PJ
AD  - Clinical Research, G1 Therapeutics, Inc., Research Triangle Park, USA.
FAU - Dragnev, K H
AU  - Dragnev KH
AD  - Department of Hematology/Oncology, Norris Cotton Cancer Center 
      Dartmouth-Hitchcock Medical Center, Lebanon, USA. Electronic address: 
      konstantin.h.dragnev@hitchcock.org.
CN  - G1T28-02 Study Group
LA  - eng
SI  - ClinicalTrials.gov/NCT02499770
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Ann Oncol
JT  - Annals of oncology : official journal of the European Society for Medical 
      Oncology
JID - 9007735
RN  - 0 (Pyrimidines)
RN  - 0 (Pyrroles)
RN  - 6PLQ3CP4P3 (Etoposide)
RN  - BG3F62OND5 (Carboplatin)
RN  - EC 2.7.11.22 (CDK4 protein, human)
RN  - EC 2.7.11.22 (CDK6 protein, human)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinase 4)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinase 6)
RN  - P88XT4IS4D (Paclitaxel)
RN  - Q20Q21Q62J (Cisplatin)
RN  - U6072DO9XG (trilaciclib)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Combined Chemotherapy Protocols/pharmacokinetics/*therapeutic use
MH  - Brain Neoplasms/*drug therapy/enzymology/secondary
MH  - Carboplatin/administration & dosage
MH  - Cisplatin/administration & dosage
MH  - Cyclin-Dependent Kinase 4/*antagonists & inhibitors
MH  - Cyclin-Dependent Kinase 6/*antagonists & inhibitors
MH  - Double-Blind Method
MH  - Etoposide/administration & dosage
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Lung Neoplasms/*drug therapy/enzymology/pathology
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Middle Aged
MH  - Myeloid Cells/*drug effects
MH  - Paclitaxel/administration & dosage
MH  - Prognosis
MH  - Pyrimidines/administration & dosage
MH  - Pyrroles/administration & dosage
MH  - Small Cell Lung Carcinoma/*drug therapy/enzymology/pathology
MH  - Survival Rate
MH  - Tissue Distribution
PMC - PMC6857609
OTO - NOTNLM
OT  - CDK4/6
OT  - anemia
OT  - myelopreservation
OT  - neutropenia
OT  - small-cell lung cancer
OT  - trilaciclib
EDAT- 2019/09/11 06:00
MHDA- 2020/08/01 06:00
PMCR- 2019/08/27
CRDT- 2019/09/11 06:00
PHST- 2019/09/11 06:00 [pubmed]
PHST- 2020/08/01 06:00 [medline]
PHST- 2019/09/11 06:00 [entrez]
PHST- 2019/08/27 00:00 [pmc-release]
AID - S0923-7534(19)60981-6 [pii]
AID - mdz278 [pii]
AID - 10.1093/annonc/mdz278 [doi]
PST - ppublish
SO  - Ann Oncol. 2019 Oct 1;30(10):1613-1621. doi: 10.1093/annonc/mdz278.