PMID- 35251315
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220502
IS  - 1758-8340 (Print)
IS  - 1758-8359 (Electronic)
IS  - 1758-8340 (Linking)
VI  - 14
DP  - 2022
TI  - First-line everolimus and cisplatin in patients with advanced extrapulmonary 
      neuroendocrine carcinoma: a nationwide phase 2 single-arm clinical trial.
PG  - 17588359221077088
LID - 10.1177/17588359221077088 [doi]
LID - 17588359221077088
AB  - BACKGROUND: Extrapulmonary neuroendocrine carcinoma (EP-NEC) are an aggressive 
      subgroup of neuroendocrine neoplasms (NEN). Advanced EP-NEC is generally treated 
      with platinum-based cytotoxic regimens, but progressive disease occurs rapidly, 
      resulting in a poor prognosis. Genetic alterations in the mammalian target for 
      rapamycin (mTOR) pathway have been identified in NEN, providing a rationale for 
      treatment with the mTOR-inhibitor everolimus. METHODS: A prospective phase 2 
      single-arm study included patients with advanced EP-NEC from three Dutch NEN 
      expertise centres between March 2016 and January 2020. Treatment consisted of 
      cisplatin 75 mg/m(2) every 3 weeks in combination with daily everolimus 7.5 mg 
      for a maximum of six cycles, followed by maintenance everolimus until disease 
      progression. Primary endpoint was disease control rate (DCR), defined as the sum 
      of overall response rate (ORR) plus the rate of stable disease according to 
      RECIST 1.1, assessed at 9-week intervals. Toxicity was evaluated according to 
      CTCAE version 5.0. RESULTS: Thirty-nine patients, with a median age of 64 years 
      (range: 28-74), of whom 20 (51%) were male, were enrolled. DCR was 82.1% (95% 
      confidence interval (CI): 66.4-92.4), with an ORR of 58.9% (CI: 42.1-74.4). 
      Median duration of response was 6.4 (CI: 5.8-7.0) months and median 
      progression-free survival was 6.0 (CI: 4.3-7.8) months. Three patients (8%) had 
      durable responses lasting  > 12 months. Median overall survival was 8.7 (CI: 
      7.8-9.6) months. Most common grade 3/4 toxicities were haematological (36%) and 
      renal (21%). CONCLUSION: Everolimus in combination with cisplatin is an effective 
      first-line treatment option for advanced EP-NEC, especially in highly selected 
      patients. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02695459, 
      https://clinicaltrials.gov/ct2/show/NCT02695459.
CI  - (c) The Author(s), 2022.
FAU - Levy, Sonja
AU  - Levy S
AD  - Department of Medical Oncology, Netherlands Cancer Institute, Plesmanlaan 121, 
      1066CX Amsterdam, The Netherlands.
FAU - Verbeek, Wieke H M
AU  - Verbeek WHM
AD  - Department of Gastroenterological Oncology, Netherlands Cancer Institute, 
      Amsterdam, The Netherlands.
FAU - Eskens, Ferry A L M
AU  - Eskens FALM
AD  - Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The 
      Netherlands.
FAU - van den Berg, Jose G
AU  - van den Berg JG
AD  - Department of Pathology, Netherlands Cancer Institute, Amsterdam, The 
      Netherlands.
FAU - de Groot, Derk Jan A
AU  - de Groot DJA
AD  - Department of Medical Oncology, University Medical Centre Groningen, Groningen, 
      The Netherlands.
FAU - van Leerdam, Monique E
AU  - van Leerdam ME
AD  - Department of Gastroenterological Oncology, Netherlands Cancer Institute, 
      Amsterdam, The Netherlands.
FAU - Tesselaar, Margot E T
AU  - Tesselaar MET
AD  - Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The 
      Netherlands.
LA  - eng
SI  - ClinicalTrials.gov/NCT02695459
PT  - Journal Article
DEP - 20220227
PL  - England
TA  - Ther Adv Med Oncol
JT  - Therapeutic advances in medical oncology
JID - 101510808
PMC - PMC8891910
OTO - NOTNLM
OT  - cisplatin
OT  - everolimus
OT  - neuroendocrine carcinoma
COIS- Conflict of interest statement: The authors declared no potential conflicts of 
      interest with respect to the research, authorship and/or publication of this 
      article.
EDAT- 2022/03/08 06:00
MHDA- 2022/03/08 06:01
PMCR- 2022/02/27
CRDT- 2022/03/07 06:04
PHST- 2021/10/11 00:00 [received]
PHST- 2022/01/12 00:00 [accepted]
PHST- 2022/03/07 06:04 [entrez]
PHST- 2022/03/08 06:00 [pubmed]
PHST- 2022/03/08 06:01 [medline]
PHST- 2022/02/27 00:00 [pmc-release]
AID - 10.1177_17588359221077088 [pii]
AID - 10.1177/17588359221077088 [doi]
PST - epublish
SO  - Ther Adv Med Oncol. 2022 Feb 27;14:17588359221077088. doi: 
      10.1177/17588359221077088. eCollection 2022.