PMID- 32479189
OWN - NLM
STAT- MEDLINE
DCOM- 20210226
LR  - 20221029
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Print)
IS  - 0732-183X (Linking)
VI  - 38
IP  - 21
DP  - 2020 Jul 20
TI  - Safety and Efficacy of Pembrolizumab With Chemoradiotherapy in Locally Advanced 
      Head and Neck Squamous Cell Carcinoma: A Phase IB Study.
PG  - 2427-2437
LID - 10.1200/JCO.19.03156 [doi]
AB  - PURPOSE: Pembrolizumab is a humanized monoclonal antibody that blocks interaction 
      between programmed death receptor-1 (PD-1) and its ligands (PD-L1, PD-L2). 
      Although pembrolizumab is approved for recurrent/metastatic head and neck 
      squamous cell carcinoma (HNSCC), its role in the management of locally advanced 
      (LA) disease is not defined. We report a phase IB study evaluating the safety and 
      efficacy of adding pembrolizumab to cisplatin-based chemoradiotherapy in patients 
      with LA HNSCC. PATIENTS AND METHODS: Eligible patients included those with oral 
      cavity (excluding lip), oropharyngeal, hypopharyngeal, or laryngeal stage III to 
      IVB HNSCC (according to American Joint Committee on Cancer, 7th edition, staging 
      system) eligible for cisplatin-based, standard-dose (70 Gy) chemoradiotherapy. 
      Pembrolizumab was administered concurrently with and after chemoradiotherapy with 
      weekly cisplatin. Safety was the primary end point and was determined by 
      incidence of chemoradiotherapy adverse events (AEs) and immune-related AEs 
      (irAEs). Efficacy was defined as complete response (CR) rate on end-of-treatment 
      (EOT) imaging or with pathologic confirmation at 100 days postradiotherapy 
      completion. Key secondary end points included overall (OS) and progression-free 
      survival (PFS). RESULTS: The study accrued 59 patients (human papillomavirus 
      [HPV] positive, n = 34; HPV negative, n = 25) from November 2015 to October 2018. 
      Five patients (8.8%) required discontinuation of pembrolizumab because of irAEs, 
      all of which occurred during concurrent chemoradiotherapy; 98.3% of patients 
      completed the full planned treatment dose (70 Gy) of radiotherapy without any 
      delays >/= 5 days; 88.1% of patients completed the goal cisplatin dose of >/= 200 
      mg/m(2). EOT CR rates were 85.3% and 78.3% for those with HPV-positive and 
      -negative HNSCC, respectively. CONCLUSION: Pembrolizumab in combination with 
      weekly cisplatin-based chemoradiotherapy is safe and does not impair delivery of 
      curative radiotherapy or chemotherapy in HNSCC. Early efficacy data support 
      further investigation of this approach.
FAU - Powell, Steven F
AU  - Powell SF
AD  - Sanford Cancer Center, Sanford Health, Sioux Falls, SD.
FAU - Gold, Kathryn A
AU  - Gold KA
AD  - Moores Cancer Center, University of California San Diego, La Jolla, CA.
FAU - Gitau, Mark M
AU  - Gitau MM
AD  - Roger Maris Cancer Center, Sanford Health, Fargo, ND.
FAU - Sumey, Christopher J
AU  - Sumey CJ
AD  - Sanford Cancer Center, Sanford Health, Sioux Falls, SD.
FAU - Lohr, Michele M
AU  - Lohr MM
AD  - Sanford Cancer Center, Sanford Health, Sioux Falls, SD.
FAU - McGraw, Steven C
AU  - McGraw SC
AD  - Sanford Cancer Center, Sanford Health, Sioux Falls, SD.
FAU - Nowak, Ryan K
AU  - Nowak RK
AD  - Sanford Cancer Center, Sanford Health, Sioux Falls, SD.
FAU - Jensen, Ashley W
AU  - Jensen AW
AD  - Roger Maris Cancer Center, Sanford Health, Fargo, ND.
FAU - Blanchard, Miran J
AU  - Blanchard MJ
AD  - Roger Maris Cancer Center, Sanford Health, Fargo, ND.
FAU - Fischer, Christopher D
AU  - Fischer CD
AD  - Radiology, Sanford Health, Sioux Falls, SD.
FAU - Bykowski, Julie
AU  - Bykowski J
AD  - Moores Cancer Center, University of California San Diego, La Jolla, CA.
FAU - Ellison, Christie A
AU  - Ellison CA
AD  - Sanford Research, Sanford Health, Sioux Falls, SD.
FAU - Black, Lora J
AU  - Black LJ
AD  - Sanford Research, Sanford Health, Sioux Falls, SD.
FAU - Thompson, Paul A
AU  - Thompson PA
AD  - Sanford Research, Sanford Health, Sioux Falls, SD.
FAU - Callejas-Valera, Juan L
AU  - Callejas-Valera JL
AD  - Sanford Research, Sanford Health, Sioux Falls, SD.
FAU - Lee, John H
AU  - Lee JH
AD  - ImmunityBio, Culver City, CA.
FAU - Cohen, Ezra E W
AU  - Cohen EEW
AD  - Moores Cancer Center, University of California San Diego, La Jolla, CA.
FAU - Spanos, William C
AU  - Spanos WC
AD  - Sanford Cancer Center, Sanford Health, Sioux Falls, SD.
LA  - eng
SI  - ClinicalTrials.gov/NCT02586207
GR  - P20 GM103548/GM/NIGMS NIH HHS/United States
GR  - P30 CA023100/CA/NCI NIH HHS/United States
GR  - R01 DE026125/DE/NIDCR NIH HHS/United States
GR  - R01 DE029524/DE/NIDCR NIH HHS/United States
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20200601
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  - DPT0O3T46P (pembrolizumab)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antibodies, Monoclonal, Humanized/pharmacology/*therapeutic use
MH  - Antineoplastic Agents, Immunological/pharmacology/*therapeutic use
MH  - Chemoradiotherapy/*methods
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Retrospective Studies
MH  - Squamous Cell Carcinoma of Head and Neck/*drug therapy/*radiotherapy
PMC - PMC7365766
MID - NIHMS1602423
EDAT- 2020/06/02 06:00
MHDA- 2021/02/27 06:00
PMCR- 2020/06/01
CRDT- 2020/06/02 06:00
PHST- 2020/06/02 06:00 [pubmed]
PHST- 2021/02/27 06:00 [medline]
PHST- 2020/06/02 06:00 [entrez]
PHST- 2020/06/01 00:00 [pmc-release]
AID - 1903156 [pii]
AID - 10.1200/JCO.19.03156 [doi]
PST - ppublish
SO  - J Clin Oncol. 2020 Jul 20;38(21):2427-2437. doi: 10.1200/JCO.19.03156. Epub 2020 
      Jun 1.