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ESMO Open. 2018 Jul 23;3(5):e000388. doi: 10.1136/esmoopen-2018-000388. eCollection 2018.

Phase I, open-label study of pasireotide in patients with BRAF-wild type and NRAS-wild type, unresectable and/or metastatic melanoma.

Author information

1
Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
2
Multidisciplinary Oncology Center, Lausanne University Hospital (CHUV), Lausanne, Switzerland.
3
Global Medical Affairs, Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA.
4
Clinical Development, Novartis Pharma AG, Basel, Switzerland.
5
Department of Dermatology, University Hospital Essen, Essen, Germany & German Cancer Consortium, Heidelberg, Germany.

Abstract

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 µg in dose-escalation and follow-up phases and two patients reached 3600 µg 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.

KEYWORDS:

MAPK; braf- and nras-wild type; insulin-like growth factor-1; metastatic melanoma; pasireotide

Conflict of interest statement

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.

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