PMID- 30407895
OWN - NLM
STAT- In-Data-Review
LR  - 20190610
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Linking)
VI  - 37
IP  - 1
DP  - 2019 Jan 1
TI  - Long-Term Survival of Patients With Melanoma With Active Brain Metastases Treated
      With Pembrolizumab on a Phase II Trial.
PG  - 52-60
LID - 10.1200/JCO.18.00204 [doi]
AB  - PURPOSE: Pembrolizumab is active in melanoma, but activity in patients with
      untreated brain metastasis is less established. We present long-term follow-up of
      pembrolizumab-treated patients with new or progressing brain metastases treated
      on a phase II clinical trial ( ClinicalTrials.gov identifier: NCT02085070).
      PATIENTS AND METHODS: We enrolled 23 patients with melanoma with one or more
      asymptomatic, untreated 5- to 20-mm brain metastasis not requiring
      corticosteroids; 70% of patients had prior systemic therapy. Pembrolizumab was
      administered for up to 24 months. Brain metastasis response, the primary end
      point, was assessed by modified Response Evaluation Criteria in Solid Tumors
      (RECIST). Pretreatment tumors were analyzed for T-cell infiltrate and programmed 
      death ligand 1. RESULTS: Six patients (26%) had a brain metastasis response.
      Eight patients (35%) did not reach a protocol evaluation scan and were
      unevaluable for brain metastasis response as a result of progression or need for 
      radiation. Brain metastasis and systemic responses were concordant, with all
      ongoing at 24 months. The median progression-free and overall survival times were
      2 and 17 months, respectively. Eleven patients (48%) were alive at 24 months.
      This included three unevaluable patients. One of these three patients had
      hemorrhaged, and two had symptoms from perilesional edema requiring radiosurgery,
      but all three patients remained on commercial pembrolizumab more than 24 months
      later. None of the 24-month survivors received subsequent BRAF inhibitors.
      Neurologic adverse events occurred in 65% of patients; all adverse events but one
      were grade 1 or 2. Three patients had seizures, which were treated with
      anticonvulsants. Most responders had higher pretreatment tumor CD8 cell density
      and programmed death ligand 1 expression, whereas all nonresponders did not.
      CONCLUSION: Pembrolizumab is active in melanoma brain metastases with acceptable 
      toxicity and durable responses. Multidisciplinary care is required to optimally
      manage patients with brain metastases, including consideration of radiation to
      large or symptomatic lesions, which were excluded in this trial. Two-year
      survival was similar to patients without brain metastasis treated with
      anti-programmed cell death 1 agents. Concordant brain and extracerebral responses
      support use of pembrolizumab to treat small, asymptomatic brain metastases.
FAU - Kluger, Harriet M
AU  - Kluger HM
AD  - 1 Yale University School of Medicine and Yale Cancer Center, New Haven, CT.
FAU - Chiang, Veronica
AU  - Chiang V
AD  - 1 Yale University School of Medicine and Yale Cancer Center, New Haven, CT.
FAU - Mahajan, Amit
AU  - Mahajan A
AD  - 1 Yale University School of Medicine and Yale Cancer Center, New Haven, CT.
FAU - Zito, Christopher R
AU  - Zito CR
AD  - 1 Yale University School of Medicine and Yale Cancer Center, New Haven, CT.
FAU - Sznol, Mario
AU  - Sznol M
AD  - 1 Yale University School of Medicine and Yale Cancer Center, New Haven, CT.
FAU - Tran, Thuy
AU  - Tran T
AD  - 1 Yale University School of Medicine and Yale Cancer Center, New Haven, CT.
FAU - Weiss, Sarah A
AU  - Weiss SA
AD  - 1 Yale University School of Medicine and Yale Cancer Center, New Haven, CT.
FAU - Cohen, Justine V
AU  - Cohen JV
AD  - 1 Yale University School of Medicine and Yale Cancer Center, New Haven, CT.
FAU - Yu, James
AU  - Yu J
AD  - 1 Yale University School of Medicine and Yale Cancer Center, New Haven, CT.
FAU - Hegde, Upendra
AU  - Hegde U
AD  - 1 Yale University School of Medicine and Yale Cancer Center, New Haven, CT.
FAU - Perrotti, Elizabeth
AU  - Perrotti E
AD  - 1 Yale University School of Medicine and Yale Cancer Center, New Haven, CT.
FAU - Anderson, Gail
AU  - Anderson G
AD  - 1 Yale University School of Medicine and Yale Cancer Center, New Haven, CT.
FAU - Ralabate, Amanda
AU  - Ralabate A
AD  - 1 Yale University School of Medicine and Yale Cancer Center, New Haven, CT.
FAU - Kluger, Yuval
AU  - Kluger Y
AD  - 1 Yale University School of Medicine and Yale Cancer Center, New Haven, CT.
FAU - Wei, Wei
AU  - Wei W
AD  - 1 Yale University School of Medicine and Yale Cancer Center, New Haven, CT.
FAU - Goldberg, Sarah B
AU  - Goldberg SB
AD  - 1 Yale University School of Medicine and Yale Cancer Center, New Haven, CT.
FAU - Jilaveanu, Lucia B
AU  - Jilaveanu LB
AD  - 1 Yale University School of Medicine and Yale Cancer Center, New Haven, CT.
LA  - eng
SI  - ClinicalTrials.gov/NCT02085070
GR  - R01 CA204002/CA/NCI NIH HHS/United States
GR  - R01 CA216846/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20181108
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of
      Clinical Oncology
JID - 8309333
PMC - PMC6354772
EDAT- 2018/11/09 06:00
MHDA- 2018/11/09 06:00
CRDT- 2018/11/09 06:00
PMCR- 2020/01/01 00:00
PHST- 2020/01/01 00:00 [pmc-release]
PHST- 2018/11/09 06:00 [pubmed]
PHST- 2018/11/09 06:00 [medline]
PHST- 2018/11/09 06:00 [entrez]
AID - 10.1200/JCO.18.00204 [doi]
PST - ppublish
SO  - J Clin Oncol. 2019 Jan 1;37(1):52-60. doi: 10.1200/JCO.18.00204. Epub 2018 Nov 8.