PMID- 29095678
OWN - NLM
STAT- MEDLINE
DCOM- 20171219
LR  - 20210503
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Linking)
VI  - 35
IP  - 36
DP  - 2017 Dec 20
TI  - Safety and Efficacy of Pembrolizumab in Advanced, Programmed Death Ligand 
      1-Positive Cervical Cancer: Results From the Phase Ib KEYNOTE-028 Trial.
PG  - 4035-4041
LID - 10.1200/JCO.2017.74.5471 [doi]
AB  - Purpose The KEYNOTE-028 trial ( ClinicalTrials.gov identifier: NCT02054806) was 
      designed to assess the safety and efficacy of pembrolizumab in 20 programmed 
      death ligand 1-positive, advanced solid tumor cohorts. Here, we present the 
      results from the cohort of patients with advanced cervical cancer. Methods 
      Patients were treated with pembrolizumab 10 mg/kg every 2 weeks for up to 24 
      months. Response was assessed every 8 weeks for the first 6 months and every 12 
      weeks thereafter. The primary end point was overall response rate per Response 
      Evaluation Criteria in Solid Tumors, version 1.1, by investigator review. Safety 
      was a secondary end point. Results Twenty-four patients were enrolled in the 
      cervical cancer cohort. The median age was 42 years (range, 26 to 62 years), 22 
      patients (92%) had received prior radiation therapy, and 15 patients (63%) had 
      received two or more lines of therapy, including bevacizumab (10 of 24 patients), 
      for advanced disease. At the data cutoff, median follow-up duration was 11.0 
      months (range, 1.3 to 32.2 months). Overall response rate was 17% (95% CI, 5% to 
      37%); four patients (17%) achieved a confirmed partial response, and three 
      patients (13%) had stable disease. Median duration of response for the four 
      patients who achieved a partial response was 5.4 months (4.1 to 7.5 months). 
      Treatment related adverse events (AEs) were experienced by 18 patients (75%); 
      only rash (n = 5; 21%) and pyrexia (n = 4; 17%) and occurred in >/= 10% of 
      patients. Five patients experienced grade 3 treatment-related AEs. No grade 4 
      treatment-related AEs or deaths were observed. Conclusion In patients with 
      programmed death ligand 1-positive advanced cervical cancer, pembrolizumab 
      demonstrated antitumor activity and exhibited a safety profile consistent with 
      that seen in other tumor types.
FAU - Frenel, Jean-Sebastien
AU  - Frenel JS
AD  - Jean-Sebastien Frenel, Institut de Cancerologie de l'Ouest, Centre Rene 
      Gauducheau, Saint-Herblain; Christophe Le Tourneau, Institut Curie, Paris and 
      Saint-Cloud, and Institut National de la Sante et de la Recherche Medicale U900 
      Research Unit, Saint-Cloud; Carlos Gomez-Roca, Institut Claudius Regaud, 
      Toulouse; Andrea Varga, Gustave Roussy, Villejuif, France; Bert O'Neil, Indiana 
      University Health University Hospital, Indianapolis, IN; Patrick A. Ott, 
      Dana-Farber Cancer Institute, Boston, MA; Sarina A. Piha-Paul, The University of 
      Texas MD Anderson Cancer Center, Houston, TX; Emilie M.J. van Brummelen, The 
      Netherlands Cancer Institute, Amsterdam, Netherlands; Hope S. Rugo, University of 
      California, San Francisco, San Francisco, CA; and Shari Thomas, Sanatan Saraf, 
      and Reshma Rangwala, Merck & Co., Inc., Kenilworth, NJ.
FAU - Le Tourneau, Christophe
AU  - Le Tourneau C
AD  - Jean-Sebastien Frenel, Institut de Cancerologie de l'Ouest, Centre Rene 
      Gauducheau, Saint-Herblain; Christophe Le Tourneau, Institut Curie, Paris and 
      Saint-Cloud, and Institut National de la Sante et de la Recherche Medicale U900 
      Research Unit, Saint-Cloud; Carlos Gomez-Roca, Institut Claudius Regaud, 
      Toulouse; Andrea Varga, Gustave Roussy, Villejuif, France; Bert O'Neil, Indiana 
      University Health University Hospital, Indianapolis, IN; Patrick A. Ott, 
      Dana-Farber Cancer Institute, Boston, MA; Sarina A. Piha-Paul, The University of 
      Texas MD Anderson Cancer Center, Houston, TX; Emilie M.J. van Brummelen, The 
      Netherlands Cancer Institute, Amsterdam, Netherlands; Hope S. Rugo, University of 
      California, San Francisco, San Francisco, CA; and Shari Thomas, Sanatan Saraf, 
      and Reshma Rangwala, Merck & Co., Inc., Kenilworth, NJ.
FAU - O'Neil, Bert
AU  - O'Neil B
AD  - Jean-Sebastien Frenel, Institut de Cancerologie de l'Ouest, Centre Rene 
      Gauducheau, Saint-Herblain; Christophe Le Tourneau, Institut Curie, Paris and 
      Saint-Cloud, and Institut National de la Sante et de la Recherche Medicale U900 
      Research Unit, Saint-Cloud; Carlos Gomez-Roca, Institut Claudius Regaud, 
      Toulouse; Andrea Varga, Gustave Roussy, Villejuif, France; Bert O'Neil, Indiana 
      University Health University Hospital, Indianapolis, IN; Patrick A. Ott, 
      Dana-Farber Cancer Institute, Boston, MA; Sarina A. Piha-Paul, The University of 
      Texas MD Anderson Cancer Center, Houston, TX; Emilie M.J. van Brummelen, The 
      Netherlands Cancer Institute, Amsterdam, Netherlands; Hope S. Rugo, University of 
      California, San Francisco, San Francisco, CA; and Shari Thomas, Sanatan Saraf, 
      and Reshma Rangwala, Merck & Co., Inc., Kenilworth, NJ.
FAU - Ott, Patrick A
AU  - Ott PA
AD  - Jean-Sebastien Frenel, Institut de Cancerologie de l'Ouest, Centre Rene 
      Gauducheau, Saint-Herblain; Christophe Le Tourneau, Institut Curie, Paris and 
      Saint-Cloud, and Institut National de la Sante et de la Recherche Medicale U900 
      Research Unit, Saint-Cloud; Carlos Gomez-Roca, Institut Claudius Regaud, 
      Toulouse; Andrea Varga, Gustave Roussy, Villejuif, France; Bert O'Neil, Indiana 
      University Health University Hospital, Indianapolis, IN; Patrick A. Ott, 
      Dana-Farber Cancer Institute, Boston, MA; Sarina A. Piha-Paul, The University of 
      Texas MD Anderson Cancer Center, Houston, TX; Emilie M.J. van Brummelen, The 
      Netherlands Cancer Institute, Amsterdam, Netherlands; Hope S. Rugo, University of 
      California, San Francisco, San Francisco, CA; and Shari Thomas, Sanatan Saraf, 
      and Reshma Rangwala, Merck & Co., Inc., Kenilworth, NJ.
FAU - Piha-Paul, Sarina A
AU  - Piha-Paul SA
AD  - Jean-Sebastien Frenel, Institut de Cancerologie de l'Ouest, Centre Rene 
      Gauducheau, Saint-Herblain; Christophe Le Tourneau, Institut Curie, Paris and 
      Saint-Cloud, and Institut National de la Sante et de la Recherche Medicale U900 
      Research Unit, Saint-Cloud; Carlos Gomez-Roca, Institut Claudius Regaud, 
      Toulouse; Andrea Varga, Gustave Roussy, Villejuif, France; Bert O'Neil, Indiana 
      University Health University Hospital, Indianapolis, IN; Patrick A. Ott, 
      Dana-Farber Cancer Institute, Boston, MA; Sarina A. Piha-Paul, The University of 
      Texas MD Anderson Cancer Center, Houston, TX; Emilie M.J. van Brummelen, The 
      Netherlands Cancer Institute, Amsterdam, Netherlands; Hope S. Rugo, University of 
      California, San Francisco, San Francisco, CA; and Shari Thomas, Sanatan Saraf, 
      and Reshma Rangwala, Merck & Co., Inc., Kenilworth, NJ.
FAU - Gomez-Roca, Carlos
AU  - Gomez-Roca C
AD  - Jean-Sebastien Frenel, Institut de Cancerologie de l'Ouest, Centre Rene 
      Gauducheau, Saint-Herblain; Christophe Le Tourneau, Institut Curie, Paris and 
      Saint-Cloud, and Institut National de la Sante et de la Recherche Medicale U900 
      Research Unit, Saint-Cloud; Carlos Gomez-Roca, Institut Claudius Regaud, 
      Toulouse; Andrea Varga, Gustave Roussy, Villejuif, France; Bert O'Neil, Indiana 
      University Health University Hospital, Indianapolis, IN; Patrick A. Ott, 
      Dana-Farber Cancer Institute, Boston, MA; Sarina A. Piha-Paul, The University of 
      Texas MD Anderson Cancer Center, Houston, TX; Emilie M.J. van Brummelen, The 
      Netherlands Cancer Institute, Amsterdam, Netherlands; Hope S. Rugo, University of 
      California, San Francisco, San Francisco, CA; and Shari Thomas, Sanatan Saraf, 
      and Reshma Rangwala, Merck & Co., Inc., Kenilworth, NJ.
FAU - van Brummelen, Emilie M J
AU  - van Brummelen EMJ
AD  - Jean-Sebastien Frenel, Institut de Cancerologie de l'Ouest, Centre Rene 
      Gauducheau, Saint-Herblain; Christophe Le Tourneau, Institut Curie, Paris and 
      Saint-Cloud, and Institut National de la Sante et de la Recherche Medicale U900 
      Research Unit, Saint-Cloud; Carlos Gomez-Roca, Institut Claudius Regaud, 
      Toulouse; Andrea Varga, Gustave Roussy, Villejuif, France; Bert O'Neil, Indiana 
      University Health University Hospital, Indianapolis, IN; Patrick A. Ott, 
      Dana-Farber Cancer Institute, Boston, MA; Sarina A. Piha-Paul, The University of 
      Texas MD Anderson Cancer Center, Houston, TX; Emilie M.J. van Brummelen, The 
      Netherlands Cancer Institute, Amsterdam, Netherlands; Hope S. Rugo, University of 
      California, San Francisco, San Francisco, CA; and Shari Thomas, Sanatan Saraf, 
      and Reshma Rangwala, Merck & Co., Inc., Kenilworth, NJ.
FAU - Rugo, Hope S
AU  - Rugo HS
AD  - Jean-Sebastien Frenel, Institut de Cancerologie de l'Ouest, Centre Rene 
      Gauducheau, Saint-Herblain; Christophe Le Tourneau, Institut Curie, Paris and 
      Saint-Cloud, and Institut National de la Sante et de la Recherche Medicale U900 
      Research Unit, Saint-Cloud; Carlos Gomez-Roca, Institut Claudius Regaud, 
      Toulouse; Andrea Varga, Gustave Roussy, Villejuif, France; Bert O'Neil, Indiana 
      University Health University Hospital, Indianapolis, IN; Patrick A. Ott, 
      Dana-Farber Cancer Institute, Boston, MA; Sarina A. Piha-Paul, The University of 
      Texas MD Anderson Cancer Center, Houston, TX; Emilie M.J. van Brummelen, The 
      Netherlands Cancer Institute, Amsterdam, Netherlands; Hope S. Rugo, University of 
      California, San Francisco, San Francisco, CA; and Shari Thomas, Sanatan Saraf, 
      and Reshma Rangwala, Merck & Co., Inc., Kenilworth, NJ.
FAU - Thomas, Shari
AU  - Thomas S
AD  - Jean-Sebastien Frenel, Institut de Cancerologie de l'Ouest, Centre Rene 
      Gauducheau, Saint-Herblain; Christophe Le Tourneau, Institut Curie, Paris and 
      Saint-Cloud, and Institut National de la Sante et de la Recherche Medicale U900 
      Research Unit, Saint-Cloud; Carlos Gomez-Roca, Institut Claudius Regaud, 
      Toulouse; Andrea Varga, Gustave Roussy, Villejuif, France; Bert O'Neil, Indiana 
      University Health University Hospital, Indianapolis, IN; Patrick A. Ott, 
      Dana-Farber Cancer Institute, Boston, MA; Sarina A. Piha-Paul, The University of 
      Texas MD Anderson Cancer Center, Houston, TX; Emilie M.J. van Brummelen, The 
      Netherlands Cancer Institute, Amsterdam, Netherlands; Hope S. Rugo, University of 
      California, San Francisco, San Francisco, CA; and Shari Thomas, Sanatan Saraf, 
      and Reshma Rangwala, Merck & Co., Inc., Kenilworth, NJ.
FAU - Saraf, Sanatan
AU  - Saraf S
AD  - Jean-Sebastien Frenel, Institut de Cancerologie de l'Ouest, Centre Rene 
      Gauducheau, Saint-Herblain; Christophe Le Tourneau, Institut Curie, Paris and 
      Saint-Cloud, and Institut National de la Sante et de la Recherche Medicale U900 
      Research Unit, Saint-Cloud; Carlos Gomez-Roca, Institut Claudius Regaud, 
      Toulouse; Andrea Varga, Gustave Roussy, Villejuif, France; Bert O'Neil, Indiana 
      University Health University Hospital, Indianapolis, IN; Patrick A. Ott, 
      Dana-Farber Cancer Institute, Boston, MA; Sarina A. Piha-Paul, The University of 
      Texas MD Anderson Cancer Center, Houston, TX; Emilie M.J. van Brummelen, The 
      Netherlands Cancer Institute, Amsterdam, Netherlands; Hope S. Rugo, University of 
      California, San Francisco, San Francisco, CA; and Shari Thomas, Sanatan Saraf, 
      and Reshma Rangwala, Merck & Co., Inc., Kenilworth, NJ.
FAU - Rangwala, Reshma
AU  - Rangwala R
AD  - Jean-Sebastien Frenel, Institut de Cancerologie de l'Ouest, Centre Rene 
      Gauducheau, Saint-Herblain; Christophe Le Tourneau, Institut Curie, Paris and 
      Saint-Cloud, and Institut National de la Sante et de la Recherche Medicale U900 
      Research Unit, Saint-Cloud; Carlos Gomez-Roca, Institut Claudius Regaud, 
      Toulouse; Andrea Varga, Gustave Roussy, Villejuif, France; Bert O'Neil, Indiana 
      University Health University Hospital, Indianapolis, IN; Patrick A. Ott, 
      Dana-Farber Cancer Institute, Boston, MA; Sarina A. Piha-Paul, The University of 
      Texas MD Anderson Cancer Center, Houston, TX; Emilie M.J. van Brummelen, The 
      Netherlands Cancer Institute, Amsterdam, Netherlands; Hope S. Rugo, University of 
      California, San Francisco, San Francisco, CA; and Shari Thomas, Sanatan Saraf, 
      and Reshma Rangwala, Merck & Co., Inc., Kenilworth, NJ.
FAU - Varga, Andrea
AU  - Varga A
AD  - Jean-Sebastien Frenel, Institut de Cancerologie de l'Ouest, Centre Rene 
      Gauducheau, Saint-Herblain; Christophe Le Tourneau, Institut Curie, Paris and 
      Saint-Cloud, and Institut National de la Sante et de la Recherche Medicale U900 
      Research Unit, Saint-Cloud; Carlos Gomez-Roca, Institut Claudius Regaud, 
      Toulouse; Andrea Varga, Gustave Roussy, Villejuif, France; Bert O'Neil, Indiana 
      University Health University Hospital, Indianapolis, IN; Patrick A. Ott, 
      Dana-Farber Cancer Institute, Boston, MA; Sarina A. Piha-Paul, The University of 
      Texas MD Anderson Cancer Center, Houston, TX; Emilie M.J. van Brummelen, The 
      Netherlands Cancer Institute, Amsterdam, Netherlands; Hope S. Rugo, University of 
      California, San Francisco, San Francisco, CA; and Shari Thomas, Sanatan Saraf, 
      and Reshma Rangwala, Merck & Co., Inc., Kenilworth, NJ.
LA  - eng
SI  - ClinicalTrials.gov/NCT02054806
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
DEP - 20171102
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antineoplastic Agents, Immunological)
RN  - 0 (B7-H1 Antigen)
RN  - 0 (CD274 protein, human)
RN  - DPT0O3T46P (pembrolizumab)
SB  - IM
MH  - Adult
MH  - Antibodies, Monoclonal, Humanized/*administration & dosage/adverse effects
MH  - Antineoplastic Agents, Immunological/administration & dosage/adverse effects
MH  - B7-H1 Antigen/*biosynthesis/immunology
MH  - Cohort Studies
MH  - Disease-Free Survival
MH  - Drug Administration Schedule
MH  - Female
MH  - Humans
MH  - Infusions, Intravenous
MH  - Kaplan-Meier Estimate
MH  - Middle Aged
MH  - Uterine Cervical Neoplasms/*drug therapy/*immunology
EDAT- 2017/11/03 06:00
MHDA- 2017/12/20 06:00
CRDT- 2017/11/03 06:00
PHST- 2017/11/03 06:00 [pubmed]
PHST- 2017/12/20 06:00 [medline]
PHST- 2017/11/03 06:00 [entrez]
AID - 10.1200/JCO.2017.74.5471 [doi]
PST - ppublish
SO  - J Clin Oncol. 2017 Dec 20;35(36):4035-4041. doi: 10.1200/JCO.2017.74.5471. Epub 
      2017 Nov 2.