Florian Eichhorn1, Laura V Klotz1, Mark Kriegsmann2, Helge Bischoff3, Marc A Schneider4, Thomas Muley4, Katharina Kriegsmann5, Uwe Haberkorn6, Claus Peter Heussel7, Rajkumar Savai8, Inka Zoernig9, Dirk Jaeger10, Michael Thomas11, Hans Hoffmann12, Hauke Winter1, Martin E Eichhorn13. 1. Department of Thoracic Surgery, Thoraxklinik, University Hospital Heidelberg, Heidelberg, Germany; Translational Lung Research Center (TLRC) Heidelberg, Member of the German Center for Lung Research (DZL), Germany. 2. Translational Lung Research Center (TLRC) Heidelberg, Member of the German Center for Lung Research (DZL), Germany; Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany. 3. Department of Thoracic Oncology, Thoraxklinik, Heidelberg University Hospital, Heidelberg, Germany. 4. Translational Lung Research Center (TLRC) Heidelberg, Member of the German Center for Lung Research (DZL), Germany; Translational Research Unit, Thoraxklinik, Heidelberg University Hospital, Heidelberg, Germany. 5. Department of Hematology, Oncology and Rheumatology, Heidelberg University, Heidelberg, Germany. 6. Translational Lung Research Center (TLRC) Heidelberg, Member of the German Center for Lung Research (DZL), Germany; Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany; Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center (DKFZ), Heidelberg, Germany. 7. Translational Lung Research Center (TLRC) Heidelberg, Member of the German Center for Lung Research (DZL), Germany; Department of Diagnostic and Interventional Radiology with Nuclear Medicine, Thoraxklinik, Heidelberg University, Heidelberg, Germany; Department of Diagnostic and Interventional Radiology, Heidelberg University, Heidelberg, Germany. 8. Department of Lung Development and Remodeling, Max Planck Institute for Heart and Lung Research, Member of the German Center for Lung Research (DZL), Member of the Cardio-Pulmonary Institute (CPI), Bad Nauheim, Germany; Institute for Lung Health (ILH), Justus Liebig University, Giessen, Germany. 9. Department of Medical Oncology and Internal Medicine VI, National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany. 10. Department of Medical Oncology and Internal Medicine VI, National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany; Clinical Cooperation Unit Applied Tumor Immunity, National Center for Tumor Diseases, German Cancer Research Center, Heidelberg, Germany. 11. Translational Lung Research Center (TLRC) Heidelberg, Member of the German Center for Lung Research (DZL), Germany; Department of Thoracic Oncology, Thoraxklinik, Heidelberg University Hospital, Heidelberg, Germany. 12. Division of Thoracic Surgery, Technical University of Munich, Munich, Germany. 13. Department of Thoracic Surgery, Thoraxklinik, University Hospital Heidelberg, Heidelberg, Germany; Translational Lung Research Center (TLRC) Heidelberg, Member of the German Center for Lung Research (DZL), Germany. Electronic address: martin.eichhorn@med.uni-heidelberg.de.
Abstract
OBJECTIVES: A phase II trial investigating the therapeutic effect of neoadjuvant programmed cell death 1 (PD-1) inhibitor pembrolizumab (MK-3475, KEYTRUDA®) administered prior to surgery for the treatment of non-small cell lung cancer (NSCLC) has been conducted (NCT03197467). We report the first clinical results of a planned interim safety analysis after 15 patients were enrolled. MATERIAL AND METHODS: Patients with resectable NSCLC stage II/IIIA were included. Two cycles of pembrolizumab (200 mg intravenously once every 3 weeks) were administered prior to surgery. The primary objectives were to assess the feasibility and safety of neoadjuvant pembrolizumab therapy and to evaluate antitumor activity. We analyzed the clinical parameters as well as pathological and radiological tumor response data. RESULTS: The NSCLC histology was adenocarcinoma for 13 patients and squamous cell carcinoma for 2 patients. All patients but two underwent 2 cycles of pembrolizumab prior to surgery. Four patients (27 %) presented a major pathologic response. Significant tumor target response in positron emission tomography computed tomography (PET-CT) was detected in all 4 pathologic responders. Nevertheless, the PET findings mismatched the tumor load in some patients. A PD-L1 expression ≥10 % in the pretreatment biopsy was associated with at least major pathologic response. Five patients (33 %) presented grade 2-3 treatment related adverse events (TRAE), the overall postoperative morbidity was 7 % and 30-day mortality was 0 %. CONCLUSION: Neoadjuvant pembrolizumab is a feasible therapy in surgical lung cancer patients. It was associated with tolerable toxicity and did not compromise tumor resection.
OBJECTIVES: A phase II trial investigating the therapeutic effect of neoadjuvant programmed cell death 1 (PD-1) inhibitor pembrolizumab (MK-3475, KEYTRUDA®) administered prior to surgery for the treatment of non-small cell lung cancer (NSCLC) has been conducted (NCT03197467). We report the first clinical results of a planned interim safety analysis after 15 patients were enrolled. MATERIAL AND METHODS: Patients with resectable NSCLC stage II/IIIA were included. Two cycles of pembrolizumab (200 mg intravenously once every 3 weeks) were administered prior to surgery. The primary objectives were to assess the feasibility and safety of neoadjuvant pembrolizumab therapy and to evaluate antitumor activity. We analyzed the clinical parameters as well as pathological and radiological tumor response data. RESULTS: The NSCLC histology was adenocarcinoma for 13 patients and squamous cell carcinoma for 2 patients. All patients but two underwent 2 cycles of pembrolizumab prior to surgery. Four patients (27 %) presented a major pathologic response. Significant tumor target response in positron emission tomography computed tomography (PET-CT) was detected in all 4 pathologic responders. Nevertheless, the PET findings mismatched the tumor load in some patients. A PD-L1 expression ≥10 % in the pretreatment biopsy was associated with at least major pathologic response. Five patients (33 %) presented grade 2-3 treatment related adverse events (TRAE), the overall postoperative morbidity was 7 % and 30-day mortality was 0 %. CONCLUSION: Neoadjuvant pembrolizumab is a feasible therapy in surgical lung cancer patients. It was associated with tolerable toxicity and did not compromise tumor resection.
Authors: Carlos Aguado; Luis Chara; Mónica Antoñanzas; Jose Maria Matilla Gonzalez; Unai Jiménez; Raul Hernanz; Xabier Mielgo-Rubio; Juan Carlos Trujillo-Reyes; Felipe Couñago Journal: World J Clin Oncol Date: 2022-05-24
Authors: Juan Jiang; Yuling Wang; Yang Gao; Haruhiko Sugimura; Fabrizio Minervini; Junji Uchino; Balazs Halmos; Sai Yendamuri; Jeffrey B Velotta; Min Li Journal: Transl Lung Cancer Res Date: 2022-02
Authors: Christopher Cao; Anthony Le; Matthew Bott; Chi-Fu Jeffrey Yang; Dominique Gossot; Franca Melfi; David H Tian; Allen Guo Journal: Curr Oncol Date: 2021-11-14 Impact factor: 3.109
Authors: Martin Faehling; Hanno Witte; Martin Sebastian; Matthias Ulmer; Rainer Sätzler; Konrad Steinestel; Wolfgang M Brückl; Georg Evers; Christian Meyer Zum Büschenfelde; Annalen Bleckmann Journal: Ther Adv Med Oncol Date: 2022-03-25 Impact factor: 8.168