Fostering efficacy of anti-PD-1-treatment: Nivolumab plus radiotherapy in advanced non-small cell lung cancer - study protocol of the FORCE trial.

Autor: Bozorgmehr F; Department of Thoracic Oncology, Thoraxklinik at University Hospital of Heidelberg, Röntgenstraße 1, 69126, Heidelberg, Germany.; Translational Lung Research Center Heidelberg TLRCH, Member of the German Center for Lung Research DZL, Im Neuenheimer Feld 156, 69120, Heidelberg, Germany., Hommertgen A; Department of Radiation Oncology, University Hospital of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany.; German Cancer Research Center, Abteilung für Molekulare Radioonkologie, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.; Heidelberg Institute of Radiation Oncology HIRO, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany., Krisam J; Institute of Medical Biometry and Informatics, University Hospital of Heidelberg, Im Neuenheimer Feld 130.3, 69120, Heidelberg, Germany., Lasitschka F; Translational Lung Research Center Heidelberg TLRCH, Member of the German Center for Lung Research DZL, Im Neuenheimer Feld 156, 69120, Heidelberg, Germany.; University Hospital of Heidelberg, Institute of Pathology, Im Neuenheimer Feld 430, 69120, Heidelberg, Germany., Kuon J; Department of Thoracic Oncology, Thoraxklinik at University Hospital of Heidelberg, Röntgenstraße 1, 69126, Heidelberg, Germany., Maenz M; AIO-Studien gGmbH, Berlin, Germany., Huber PE; German Cancer Research Center, Abteilung für Molekulare Radioonkologie, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.; Heidelberg Institute of Radiation Oncology HIRO, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany., König L; Department of Radiation Oncology, University Hospital of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany.; Heidelberg Institute of Radiation Oncology HIRO, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany., Kieser M; Institute of Medical Biometry and Informatics, University Hospital of Heidelberg, Im Neuenheimer Feld 130.3, 69120, Heidelberg, Germany., Debus J; Department of Radiation Oncology, University Hospital of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany.; German Cancer Research Center, Abteilung für Molekulare Radioonkologie, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.; Heidelberg Institute of Radiation Oncology HIRO, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany., Thomas M; Department of Thoracic Oncology, Thoraxklinik at University Hospital of Heidelberg, Röntgenstraße 1, 69126, Heidelberg, Germany.; Translational Lung Research Center Heidelberg TLRCH, Member of the German Center for Lung Research DZL, Im Neuenheimer Feld 156, 69120, Heidelberg, Germany., Rieken S; Department of Radiation Oncology, University Hospital of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany. Stefan.Rieken@med.uni-heidelberg.de.; Heidelberg Institute of Radiation Oncology HIRO, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany. Stefan.Rieken@med.uni-heidelberg.de.
Jazyk: angličtina
Zdroj: BMC cancer [BMC Cancer] 2019 Nov 08; Vol. 19 (1), pp. 1074. Date of Electronic Publication: 2019 Nov 08.
DOI: 10.1186/s12885-019-6205-0
Abstrakt: Background: Hypofractionated palliative radiotherapy for metastatic lung cancer patients is frequently used in order to ease pain, to increase bone stability, to treat local mass effects, or to prolong progression-free survival at critical sites. Recently introduced, immunotherapy for patients with non-squamous non-small cell lung carcinoma (NSCLC) has significantly improved outcome in this cohort. Preclinical and early clinical data suggest that the combination of photon radiation with programmed death-1 (PD-1) targeting immunotherapies may promote a strong and durable immune response against tumor manifestations both within and beyond radiation targets.
Methods/design: In the present prospective, two-group, non-randomized, open-label phase II trial, 130 patients with stage IV non-squamous NSCLC in 2nd-line or 3rd-line treatment will be included. 65 patients with a clinical indication for palliative radiotherapy to non-cerebral/non-pulmonary metastatic sites will receive 240 mg nivolumab followed by palliative radiotherapy with 5 × 4 Gray (Gy) = 20 Gy photon radiation, which will be initiated within 72 h after first nivolumab administration (Group A). 65 patients without an indication for radiotherapy will only receive nivolumab (Group B). Nivolumab will be further administered every two weeks in both groups and will be continued until progression and loss of clinical benefit or until occurrence of limiting toxicities. The primary endpoint will be the objective response rate (ORR) according to response evaluation criteria in solid tumors (RECIST) 1.1. Secondary endpoints will be progression-free survival (PFS) according to RECIST 1.1, overall survival, descriptive subgroup analyses according to PD-L1 expression, toxicity and quality of life. Since response patterns following immunotherapies differ from those after conventional cytostatic agents, both objective response rate and progression-free survival will additionally be assessed according to immune-related RECIST (irRECIST) criteria.
Discussion: The FORCE study will prospectively investigate response rates, progression-free and overall survival (OS), and toxicity of nivolumab with and without hypofractionated palliative radiotherapy in a group of 130 patients with metastatic non-small cell lung cancer (non-squamous histology) in 2nd-line or 3rd-line treatment. This trial will contribute prospective data to the repeatedly published observation that the combination of hypofractionated photon radiotherapy and medical immunotherapy is not only safe but will also promote antitumoral immune responses.
Trial Registration: Clinicaltrials.gov identifier: NCT03044626 (Date of initial registration: 05 January 2017). Eudra-CT Number: 2015-005741-31 (Date of initial registration: 18 December 2015).
Databáze: MEDLINE
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