Alejandro Garcia-Alvarez1, Jorge Hernando Cubero2, Jaume Capdevila2. 1. Vall d'Hebron University Hospital, Medical Oncology Department, Gastrointestinal and Endocrine Tumor Unit, Vall Hebron Institute of Oncology (VHIO), Pg Vall d'Hebron, 119-129 (08035), Barcelona, Spain. agalvarez@vhio.net. 2. Vall d'Hebron University Hospital, Medical Oncology Department, Gastrointestinal and Endocrine Tumor Unit, Vall Hebron Institute of Oncology (VHIO), Pg Vall d'Hebron, 119-129 (08035), Barcelona, Spain.
Abstract
PURPOSE OF REVIEW: Immunotherapy has changed the treatment of patients with advanced cancer, with different phase III trials showing durable responses across different histologies. This review focuses on the preclinical and clinical evidence of potential predictive biomarkers of response and efficacy of immunotherapy in neuroendocrine neoplasms (NENs) of gastro-entero-pancreatic origin. RECENT FINDINGS: PD-L1 staining by immunohistochemistry has shown heterogeneous results across different studies in both well-differentiated neuroendocrine tumors (NETs) and poorly-differentiated neuroendocrine carcinomas (NECs). Tumor mutational burden in NENs is low, but seems to be higher in NECs. Immune infiltrate (CD3+ lymphocytes) at the tumor microenvironment (TME) is present in NETs and NECs. However, results from clinical trials with immunotherapy as monotherapy o combinations have shown limited efficacy. Further investigation into new strategies aside from anti-CTLA-4/PD-1/PD-L1 antibodies, validation of predictive biomarkers, and better population selection for clinical trials in NENs are more than needed in the near future.
PURPOSE OF REVIEW: Immunotherapy has changed the treatment of patients with advanced cancer, with different phase III trials showing durable responses across different histologies. This review focuses on the preclinical and clinical evidence of potential predictive biomarkers of response and efficacy of immunotherapy in neuroendocrine neoplasms (NENs) of gastro-entero-pancreatic origin. RECENT FINDINGS: PD-L1 staining by immunohistochemistry has shown heterogeneous results across different studies in both well-differentiated neuroendocrine tumors (NETs) and poorly-differentiated neuroendocrine carcinomas (NECs). Tumor mutational burden in NENs is low, but seems to be higher in NECs. Immune infiltrate (CD3+ lymphocytes) at the tumor microenvironment (TME) is present in NETs and NECs. However, results from clinical trials with immunotherapy as monotherapy o combinations have shown limited efficacy. Further investigation into new strategies aside from anti-CTLA-4/PD-1/PD-L1 antibodies, validation of predictive biomarkers, and better population selection for clinical trials in NENs are more than needed in the near future.
Authors: James Larkin; Vanna Chiarion-Sileni; Rene Gonzalez; Jean-Jacques Grob; Piotr Rutkowski; Christopher D Lao; C Lance Cowey; Dirk Schadendorf; John Wagstaff; Reinhard Dummer; Pier F Ferrucci; Michael Smylie; David Hogg; Andrew Hill; Ivan Márquez-Rodas; John Haanen; Massimo Guidoboni; Michele Maio; Patrick Schöffski; Matteo S Carlino; Céleste Lebbé; Grant McArthur; Paolo A Ascierto; Gregory A Daniels; Georgina V Long; Lars Bastholt; Jasmine I Rizzo; Agnes Balogh; Andriy Moshyk; F Stephen Hodi; Jedd D Wolchok Journal: N Engl J Med Date: 2019-09-28 Impact factor: 91.245
Authors: Richard S Finn; Shukui Qin; Masafumi Ikeda; Peter R Galle; Michel Ducreux; Tae-You Kim; Masatoshi Kudo; Valeriy Breder; Philippe Merle; Ahmed O Kaseb; Daneng Li; Wendy Verret; Derek-Zhen Xu; Sairy Hernandez; Juan Liu; Chen Huang; Sohail Mulla; Yulei Wang; Ho Yeong Lim; Andrew X Zhu; Ann-Lii Cheng Journal: N Engl J Med Date: 2020-05-14 Impact factor: 91.245