Julien Taieb1, Markus Moehler2, Narikazu Boku3, Jaffer A Ajani4, Eduardo Yañez Ruiz5, Min-Hee Ryu6, Silke Guenther7, Vikram Chand8, Yung-Jue Bang9. 1. Sorbonne Paris Cité, Paris Decartes University, Hôpital Européen Georges-Pompidou, Paris, France. Electronic address: jtaieb75@gmail.com. 2. Johannes-Gutenberg University, Mainz, Germany. Electronic address: markus.moehler@unimedizin-mainz.de. 3. National Cancer Center Hospital, Tokyo, Japan. Electronic address: nboku@ncc.go.jp. 4. Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: jajani@mdanderson.org. 5. Instituto Clinico Oncologico del Sur, Temuco, Chile. Electronic address: eduardo.yanez@icos.cl. 6. University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea. Electronic address: miniryu@amc.seoul.kr. 7. Merck, Darmstadt, Germany. Electronic address: silke.guenther@merckgroup.com. 8. EMD Serono, Billerica, MA, USA. Electronic address: vikram.chand@emdserono.com. 9. Seoul National University College of Medicine, Seoul, South Korea. Electronic address: bangyj@snu.ac.kr.
Abstract
BACKGROUND: Standard treatment options for patients with advanced gastric or gastroesophageal junction cancer (GC/GEJC) are associated with limited efficacy and some toxicity. Recently, immunotherapy with antibodies that inhibit the programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) interaction has emerged as a new treatment option. This manuscript reviews early-phase and late-phase trials of immunotherapy in advanced GC/GEJC. METHODS: Searches for studies of immunotherapy in GC/GEJC were performed using PubMed, ClinicalTrials.gov, and abstract databases for select annual congresses. Findings were interpreted based on expert opinion. RESULTS: Monotherapy with anti-PD-1/PD-L1 antibodies, including pembrolizumab, nivolumab, avelumab, durvalumab, and atezolizumab, has shown interesting objective response rates (ORRs; 7-26%) across varying GC/GEJC populations, with ORRs potentially higher in PD-L1 + vs PD-L1 - tumors. Safety profiles compare favorably with chemotherapy, with grade ≥3 treatment-related adverse events occurring in 5-17%. Based on a large phase 2 study, pembrolizumab was approved in the United States for third-line treatment of patients with PD-L1 + GC/GEJC. In a phase 3 trial, third-line or later nivolumab increased overall survival vs placebo in an Asian population, leading to regulatory approval in Japan, although other completed phase 3 trials did not show superiority for pembrolizumab or avelumab monotherapy vs chemotherapy. Other trials in advanced GC/GEJC are assessing various anti-PD-1/PD-L1-based strategies, including administration in first-line and later-line settings and as combination (with chemotherapy or agents targeting other immune checkpoint proteins, eg, CTLA-4, LAG-3, and IDO) or switch-maintenance regimens. CONCLUSIONS: Anti-PD-1/PD-L1 antibodies have shown encouraging clinical activity in advanced GC/GEJC. Results from ongoing phase 3 trials are needed to further evaluate the potential roles of these agents within the continuum of care.
BACKGROUND: Standard treatment options for patients with advanced gastric or gastroesophageal junction cancer (GC/GEJC) are associated with limited efficacy and some toxicity. Recently, immunotherapy with antibodies that inhibit the programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) interaction has emerged as a new treatment option. This manuscript reviews early-phase and late-phase trials of immunotherapy in advanced GC/GEJC. METHODS: Searches for studies of immunotherapy in GC/GEJC were performed using PubMed, ClinicalTrials.gov, and abstract databases for select annual congresses. Findings were interpreted based on expert opinion. RESULTS: Monotherapy with anti-PD-1/PD-L1 antibodies, including pembrolizumab, nivolumab, avelumab, durvalumab, and atezolizumab, has shown interesting objective response rates (ORRs; 7-26%) across varying GC/GEJC populations, with ORRs potentially higher in PD-L1 + vs PD-L1 - tumors. Safety profiles compare favorably with chemotherapy, with grade ≥3 treatment-related adverse events occurring in 5-17%. Based on a large phase 2 study, pembrolizumab was approved in the United States for third-line treatment of patients with PD-L1 + GC/GEJC. In a phase 3 trial, third-line or later nivolumab increased overall survival vs placebo in an Asian population, leading to regulatory approval in Japan, although other completed phase 3 trials did not show superiority for pembrolizumab or avelumab monotherapy vs chemotherapy. Other trials in advanced GC/GEJC are assessing various anti-PD-1/PD-L1-based strategies, including administration in first-line and later-line settings and as combination (with chemotherapy or agents targeting other immune checkpoint proteins, eg, CTLA-4, LAG-3, and IDO) or switch-maintenance regimens. CONCLUSIONS: Anti-PD-1/PD-L1 antibodies have shown encouraging clinical activity in advanced GC/GEJC. Results from ongoing phase 3 trials are needed to further evaluate the potential roles of these agents within the continuum of care.
Authors: Rafael C Coelho; Pedro D P Abreu; Mariana R Monteiro; Ana Paula Stramosk; Alvaro Henrique I Garces; Andreia Cristina Melo; Marcia S Graudenz; Carlos Jose C Andrade Journal: J Glob Oncol Date: 2019-01