Spartalizumab in metastatic, well/poorly-differentiated neuroendocrine neoplasms

in Endocrine-Related Cancer
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  • 1 J Yao, Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, United States
  • 2 J Strosberg, GI Oncology, Moffitt Cancer Center, Tampa, United States
  • 3 N Fazio, Unit of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, Istituto Europeo di Oncologia, Milano, Italy
  • 4 M Pavel, Department of Medicine 1, Division of Endocrinology and Diabetology, Friedrich-Alexander Universität Erlangen-Nürnberg, Friedrich Alexander University Erlangen Nuremberg Faculty of Medicine, Erlangen, Germany
  • 5 E Bergsland, Department of Medicine, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, United States
  • 6 P Ruszniewski, Gastroenterology and Pancreatology, Hopital Beaujon, Clichy, France
  • 7 D Halperin, Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, United States
  • 8 D Li, Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, United States
  • 9 S Tafuto, Medicine, Istituto Nazionale Tumori IRCCS Fondazione Pascale, Napoli, Italy
  • 10 N Raj, Medicine, Memorial Sloan-Kettering Cancer Center, New York, 10065, United States
  • 11 D Campana, Internal Medicine and Gastroenterology, University Hospital of Bologna Sant'Orsola-Malpighi Polyclinic, Bologna, Italy
  • 12 S Hijioka, Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Japan, Chuo-ku, Japan
  • 13 M Raderer, Oncology, Medical University of Vienna Department of Internal Medicine, Wien, Vanuatu
  • 14 R Guimbaud, Oncology, CHU Toulouse Département de Médecine Nucléaire, Toulouse, France
  • 15 P Gajate, Medical Oncology, Hospital Universitario Ramon y Cajal, Madrid, 28015, Spain
  • 16 S Pusceddu, Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
  • 17 A Reising, Oncology, Novartis Pharmaceuticals Corp, East Hanover, United States
  • 18 E Degtyarev, Oncology, Novartis Pharmaceuticals Corp, East Hanover, United States
  • 19 M Shilkrut, Oncology, Novartis Pharmaceuticals Corp, East Hanover, United States
  • 20 S Eddy, Oncology, Novartis Pharmaceuticals Corp, East Hanover, United States
  • 21 S Singh, Medical Oncologist, Sunnybrook Health Sciences Centre, Toronto, Canada

Correspondence: James Yao, Email:
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Spartalizumab, a humanized anti-programmed death protein 1 (PD-1) monoclonal antibody, was evaluated in patients with well-differentiated metastatic grade 1/2 neuroendocrine tumors (NET) and poorly-differentiated gastroenteropancreatic neuroendocrine carcinomas (GEP-NEC). In this phase II, multicenter, single-arm study, patients received spartalizumab 400 mg every 4 weeks until confirmed disease progression or unacceptable toxicity. The primary endpoint was confirmed overall response rate (ORR) according to blinded independent review committee using response evaluation criteria in solid tumors 1.1. The study enrolled 95 patients in the NET group (30, 32 and 33 in the thoracic, gastrointestinal, and pancreatic cohorts, respectively), and 21 patients in the GEP-NEC group. The ORR was 7.4% (95% confidence interval [CI]: 3.0, 14.6) in the NET group (thoracic, 16.7%; gastrointestinal, 3.1%; pancreatic, 3.0%), which was below the predefined success criterion of ≥10%, and 4.8% (95% CI: 0.1, 23.8) in the GEP-NEC group. In the NET and GEP-NEC groups, the 12-month progression-free survival was 19.5% and 0%, respectively, and the 12-month overall survival was 73.5% and 19.1%, respectively. The ORR was higher in patients with ≥1% PD-L1 expression in immune/tumor cells or ≥1% CD8+ cells at baseline. The most common adverse events considered as spartalizumab-related included fatigue (29.5%) and nausea (10.5%) in the NET group, and increased aspartate and alanine aminotransferases (each 14.3%) in the GEP-NEC group. The efficacy of spartalizumab was limited in this heterogeneous and heavily pre-treated population; however, the results in the thoracic cohort is encouraging and warrants further investigation. Adverse events were manageable and consistent with previous experience.


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