Schuler et al. reported the safety and feasibility of two preoperative doses of nivolumab or nivolumab plus relatlimab without delaying curatively intended surgery in patients with resectable NSCLC. Both treatment arms were safe, and the curative resection rate was 95%. The rates of major pathological and objective radiographic responses were 27% and 10% for nivolumab and 30% and 27% for nivolumab plus relatlimab, with deeper pathological responses in patients with PD-L1-positive tumors. DFS and OS at 12 months of follow-up were 89% and 93% for nivolumab, and 93% and 100% for nivolumab plus relatlimab.
Contributed by Shishir Pant
ABSTRACT: Antibodies targeting the immune checkpoint molecules PD-1, PD-L1 and CTLA-4, administered alone or in combination with chemotherapy, are the standard of care in most patients with metastatic non-small-cell lung cancers. When given before curative surgery, tumor responses and improved event-free survival are achieved. New antibody combinations may be more efficacious and tolerable. In an ongoing, open-label phase 2 study, 60 biomarker-unselected, treatment-naive patients with resectable non-small-cell lung cancer were randomized to receive two preoperative doses of nivolumab (anti-PD-1) with or without relatlimab (anti-LAG-3) antibody therapy. The primary study endpoint was the feasibility of surgery within 43_days, which was met by all patients. Curative resection was achieved in 95% of patients. Secondary endpoints included pathological and radiographic response rates, pathologically complete resection rates, disease-free and overall survival rates, and safety. Major pathological (²10% viable tumor cells) and objective radiographic responses were achieved in 27% and 10% (nivolumab) and in 30% and 27% (nivolumab and relatlimab) of patients, respectively. In 100% (nivolumab) and 90% (nivolumab and relatlimab) of patients, tumors and lymph nodes were pathologically completely resected. With 12_months median duration of follow-up, disease-free survival and overall survival rates at 12_months were 89% and 93% (nivolumab), and 93% and 100% (nivolumab and relatlimab). Both treatments were safe with grade ³3 treatment-emergent adverse events reported in 10% and 13% of patients per study arm. Exploratory analyses provided insights into biological processes triggered by preoperative immunotherapy. This study establishes the feasibility and safety of dual targeting of PD-1 and LAG-3 before lung cancer surgery.ClinicalTrials.gov Indentifier: NCT04205552 .
Author Info: (1) West German Cancer Center, Department of Medical Oncology, University Hospital Essen, Essen, Germany. martin.schuler@uk-essen.de. Medical Faculty, University Duisburg-Essen, Es
Author Info: (1) West German Cancer Center, Department of Medical Oncology, University Hospital Essen, Essen, Germany. martin.schuler@uk-essen.de. Medical Faculty, University Duisburg-Essen, Essen, Germany. martin.schuler@uk-essen.de. National Center for Tumor Diseases (NCT) West, Essen, Germany. martin.schuler@uk-essen.de. (2) Department of Pulmonology and Thoracic Oncology, and Jessa and Science, Jessa Hospital, Hasselt, Belgium. kristof.cuppens@jessazh.be. Faculty of Medicine and Life Sciences LCRC, UHasselt, Diepenbeek, Belgium. kristof.cuppens@jessazh.be. (3) Medical Faculty, University Duisburg-Essen, Essen, Germany. West German Cancer Center, Department of Thoracic Surgery, University Medicine Essen - Ruhrlandklinik, Essen, Germany. University Hospital Carl Gustav Carus, Department of Surgery, Division of Thoracic Surgery, Technical University Dresden, Dresden, Germany. (4) West German Cancer Center, Department of Medical Oncology, University Hospital Essen, Essen, Germany. Medical Faculty, University Duisburg-Essen, Essen, Germany. National Center for Tumor Diseases (NCT) West, Essen, Germany. (5) Department of Thoracic and Vascular Surgery, Jessa Hospital, Hasselt, Belgium. (6) Medical Faculty, University Duisburg-Essen, Essen, Germany. West German Cancer Center, Department of Thoracic Surgery, University Medicine Essen - Ruhrlandklinik, Essen, Germany. (7) Medical Faculty, University Duisburg-Essen, Essen, Germany. National Center for Tumor Diseases (NCT) West, Essen, Germany. Bioinformatics and Computational Oncology, Institute for Artificial Intelligence in Medicine, University Hospital Essen, Essen, Germany. (8) Medical Faculty, University Duisburg-Essen, Essen, Germany. West German Cancer Center, Institute for Pathology, University Hospital Essen, Essen, Germany. (9) Medical Faculty, University Duisburg-Essen, Essen, Germany. National Center for Tumor Diseases (NCT) West, Essen, Germany. West German Cancer Center, Department of Pulmonary Medicine, University Medicine Essen - Ruhrlandklinik, Essen, Germany. (10) Medical Faculty, University Duisburg-Essen, Essen, Germany. West German Cancer Center, Department of Dermatology, University Hospital Essen, Essen, Germany. (11) Laboratory Medicine Department, Laboratory for Molecular Diagnostics, Jessa Hospital, Hasselt, Belgium. (12) Department of Pathology, Jessa Hospital, Hasselt, Belgium. (13) West German Cancer Center, Department of Medical Oncology, University Hospital Essen, Essen, Germany. Medical Faculty, University Duisburg-Essen, Essen, Germany. Bioinformatics and Computational Oncology, Institute for Artificial Intelligence in Medicine, University Hospital Essen, Essen, Germany. (14) Medical Faculty, University Duisburg-Essen, Essen, Germany. West German Cancer Center, Department of Dermatology, University Hospital Essen, Essen, Germany. (15) Medical Faculty, University Duisburg-Essen, Essen, Germany. National Center for Tumor Diseases (NCT) West, Essen, Germany. West German Cancer Center, Department of Nuclear Medicine, University Hospital Essen, Essen, Germany. (16) Medical Faculty, University Duisburg-Essen, Essen, Germany. West German Cancer Center, Institute for Pathology, University Hospital Essen, Essen, Germany. (17) Department of Surgery, Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. (18) Medical Faculty, University Duisburg-Essen, Essen, Germany. West German Cancer Center, Institute for Pathology, University Hospital Essen, Essen, Germany. University Hospital Frankfurt, Dr Senckenberg Institute of Pathology, Goethe University, Frankfurt, Germany. (19) Department of Thoracic Oncology, Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. (20) West German Cancer Center, Department of Medical Oncology, University Hospital Essen, Essen, Germany. Medical Faculty, University Duisburg-Essen, Essen, Germany. (21) Medical Faculty, University Duisburg-Essen, Essen, Germany. West German Cancer Center, Department of Thoracic Surgery, University Medicine Essen - Ruhrlandklinik, Essen, Germany. General Hospital Vienna, Department of Thoracic Surgery, Medical University Vienna, Vienna, Austria.
