PMID- 30094073
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220420
IS  - 2059-7029 (Print)
IS  - 2059-7029 (Electronic)
IS  - 2059-7029 (Linking)
VI  - 3
IP  - 5
DP  - 2018
TI  - Phase I, open-label study of pasireotide in patients with BRAF-wild type and 
      NRAS-wild type, unresectable and/or metastatic melanoma.
PG  - e000388
LID - S2059-7029(20)32285-7 [pii]
LID - 10.1136/esmoopen-2018-000388 [doi]
LID - e000388
AB  - INTRODUCTION: Somatostatin analogues exert antitumour activity via direct and 
      indirect mechanisms. The present study was designed to assess the safety and 
      efficacy of pasireotide in patients with BRAF-wild type (WT) and NRAS-WT 
      metastatic melanoma. PATIENTS AND METHODS: Patients with unresectable and/or 
      metastatic melanoma or Merkel cell carcinoma were eligible. Pasireotide was 
      administered at different doses for </=8 weeks in dose-escalation phase, followed 
      by long-acting pasireotide 80 mg or lower dose in case of toxicity in follow-up 
      phase up to six additional months. Primary endpoint was safety in the first 8 
      weeks of dose-escalation phase. RESULTS: The study was terminated early due to 
      slow recruitment. Of the 10 patients with metastatic melanoma enrolled, only four 
      reached the high dose level: two patients reached 3600 microg in dose-escalation and 
      follow-up phases and two patients reached 3600 microg in dose-escalation and 
      long-acting pasireotide 80 mg in follow-up phases and were stable for >5 months. 
      Most common adverse events (AEs) during dose-escalation phase in >/=2 patients 
      (20%) were: diarrhoea (50%), nausea (50%), fatigue (20%), hyperglycaemia (20%), 
      hypophosphatemia (20%), chills (20%) and tumour pain (20%). Grade 3 or 4 study 
      drug-related AEs were diarrhoea and nausea, reported in one patient. Partial 
      response was documented in one patient and stable disease in another. 
      CONCLUSIONS: Pasireotide was well tolerated, and safety results were similar to 
      those previously reported in other indications. Further studies are needed to 
      evaluate its antitumour activity alone and in combination with other drugs in 
      melanoma.
FAU - Dummer, Reinhard
AU  - Dummer R
AD  - Department of Dermatology, University Hospital Zurich, Zurich, Switzerland. 
      Electronic address: reinhard.dummer@usz.ch.
FAU - Michielin, Olivier
AU  - Michielin O
AD  - Multidisciplinary Oncology Center, Lausanne University Hospital (CHUV), Lausanne, 
      Switzerland.
FAU - Nageli, Mirjam Chantal
AU  - Nageli MC
AD  - Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
FAU - Goldinger, Simone M
AU  - Goldinger SM
AD  - Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
FAU - Campigotto, Federico
AU  - Campigotto F
AD  - Global Medical Affairs, Novartis Pharmaceuticals Corporation, East Hanover, New 
      Jersey, USA.
FAU - Kriemler-Krahn, Ulrike
AU  - Kriemler-Krahn U
AD  - Clinical Development, Novartis Pharma AG, Basel, Switzerland.
FAU - Schmid, Herbert
AU  - Schmid H
AD  - Clinical Development, Novartis Pharma AG, Basel, Switzerland.
FAU - Pedroncelli, Alberto
AU  - Pedroncelli A
AD  - Clinical Development, Novartis Pharma AG, Basel, Switzerland.
FAU - Micaletto, Sara
AU  - Micaletto S
AD  - Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
FAU - Schadendorf, Dirk
AU  - Schadendorf D
AD  - Department of Dermatology, University Hospital Essen, Essen, Germany & German 
      Cancer Consortium, Heidelberg, Germany.
LA  - eng
PT  - Journal Article
DEP - 20180723
PL  - England
TA  - ESMO Open
JT  - ESMO open
JID - 101690685
PMC - PMC6069912
OTO - NOTNLM
OT  - MAPK
OT  - braf- and nras-wild type
OT  - insulin-like growth factor-1
OT  - metastatic melanoma
OT  - pasireotide
COIS- Competing interests: RD has intermittent, project-focused consulting and/or 
      advisory relationships with Novartis, Merck Sharp & Dhome (MSD), Bristol-Myers 
      Squibb (BMS), Roche, Amgen, Takeda and Pierre Fabre outside the submitted work. 
      OM has occasional, project-focused consulting and/or advisory relationships with 
      Novartis, Merck Sharp & Dhome (MSD), Bristol-Myers Squibb (BMS), Roche, Amgen, 
      outside of the scope of the submitted work. SG reports grants and other from 
      Novartis, during the conduct of the study; personal fees and other from 
      Intermittent advisory board relationships with Novartis, Roche, MSD and BMS, 
      outside the submitted work. DS reports grants, personal fees and other from 
      Novartis, during the conduct of the study; personal fees from Amgen, GSK, BMS, 
      Roche, Amgen, Merck, Astra Zeneca, Merck-Serono and Pfizer, outside the submitted 
      work. FC reports other from Novartis Pharmaceuticals Corporation, outside the 
      submitted work. UK-K reports personal fees from Novartis Pharma AG, outside the 
      submitted work. HS reports other from Novartis Pharma AG, outside the submitted 
      work. AP reports other from Novartis Pharma AG, outside the submitted work.
EDAT- 2018/08/11 06:00
MHDA- 2018/08/11 06:01
PMCR- 2018/07/23
CRDT- 2018/08/11 06:00
PHST- 2018/04/25 00:00 [received]
PHST- 2018/05/25 00:00 [revised]
PHST- 2018/05/26 00:00 [accepted]
PHST- 2018/08/11 06:00 [entrez]
PHST- 2018/08/11 06:00 [pubmed]
PHST- 2018/08/11 06:01 [medline]
PHST- 2018/07/23 00:00 [pmc-release]
AID - S2059-7029(20)32285-7 [pii]
AID - esmoopen-2018-000388 [pii]
AID - 10.1136/esmoopen-2018-000388 [doi]
PST - epublish
SO  - ESMO Open. 2018 Jul 23;3(5):e000388. doi: 10.1136/esmoopen-2018-000388. 
      eCollection 2018.