دورية أكاديمية
Phase I Study of Stereotactic Body Radiotherapy plus Nivolumab and Urelumab or Cabiralizumab in Advanced Solid Tumors.
| العنوان: | Phase I Study of Stereotactic Body Radiotherapy plus Nivolumab and Urelumab or Cabiralizumab in Advanced Solid Tumors. |
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| المؤلفون: | Foster CC; Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, Tennessee. corey.c.foster@vumc.org schmura@radonc.uchicago.edu lukejj@upmc.edu., Fleming GF; Department of Medicine, Section of Hematology/Oncology, The University of Chicago, Chicago, Illinois., Karrison TG; Department of Public Health Sciences, The University of Chicago, Chicago, Illinois., Liao CY; Department of Public Health Sciences, The University of Chicago, Chicago, Illinois., Desai AV; Department of Pediatrics, Section of Hematology, Oncology, and Stem Cell Transplantation, The University of Chicago, Chicago, Illinois., Moroney JW; Department of Obstetrics and Gynecology, Section of Gynecologic Oncology, The University of Chicago, Chicago, Illinois., Ratain MJ; Department of Medicine, Section of Hematology/Oncology, The University of Chicago, Chicago, Illinois., Nanda R; Department of Medicine, Section of Hematology/Oncology, The University of Chicago, Chicago, Illinois., Polite BN; Department of Medicine, Section of Hematology/Oncology, The University of Chicago, Chicago, Illinois., Hahn OM; Department of Medicine, Section of Hematology/Oncology, The University of Chicago, Chicago, Illinois., O'Donnell PH; Department of Medicine, Section of Hematology/Oncology, The University of Chicago, Chicago, Illinois., Vokes EE; Department of Medicine, Section of Hematology/Oncology, The University of Chicago, Chicago, Illinois., Kindler HL; Department of Medicine, Section of Hematology/Oncology, The University of Chicago, Chicago, Illinois., Hseu R; Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, Illinois., Janisch LA; Department of Medicine, Section of Hematology/Oncology, The University of Chicago, Chicago, Illinois., Dai J; Department of Medicine, Section of Dermatology, The University of Chicago, Chicago, Illinois., Hoffman MD; Department of Medicine, Section of Dermatology, The University of Chicago, Chicago, Illinois., Weichselbaum RR; Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, Illinois.; Ludwig Center for Metastasis Research, The University of Chicago, Chicago, Illinois., Pitroda SP; Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, Illinois., Chmura SJ; Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, Illinois. corey.c.foster@vumc.org schmura@radonc.uchicago.edu lukejj@upmc.edu., Luke JJ; UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. corey.c.foster@vumc.org schmura@radonc.uchicago.edu lukejj@upmc.edu. |
| المصدر: | Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2021 Oct 15; Vol. 27 (20), pp. 5510-5518. Date of Electronic Publication: 2021 Jun 24. |
| نوع المنشور: | Clinical Trial, Phase I; Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: The Association Country of Publication: United States NLM ID: 9502500 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1557-3265 (Electronic) Linking ISSN: 10780432 NLM ISO Abbreviation: Clin Cancer Res Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Denville, NJ : The Association, c1995- |
| مواضيع طبية MeSH: | Antibodies, Monoclonal*/therapeutic use , Antineoplastic Combined Chemotherapy Protocols*/therapeutic use , Neoplasms*/pathology , Neoplasms*/therapy , Nivolumab*/therapeutic use , Radiosurgery*, Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Combined Modality Therapy ; Neoplasm Staging ; Treatment Outcome |
| مستخلص: | Purpose: CD137 agonism and CSF1R blockade augment stereotactic body radiotherapy (SBRT) and anti-programmed death-1 in preclinical models. We evaluated the safety and efficacy of SBRT with nivolumab+urelumab (CD137 agonist) or nivolumab+cabiralizumab (CSF1R inhibitor). Patients and Methods: This phase I clinical trial enrolled patients with advanced solid tumors that had progressed on standard therapies. SBRT was delivered to 1-4 metastases with nivolumab+urelumab or nivolumab+cabiralizumab given concurrently and following SBRT. Dose-limiting toxicity (DLT) was the primary endpoint with anatomic location-specific SBRT doses deemed safe if ≤33% DLT frequency was observed. Secondary endpoints included RECISTv1.1 response, progression-free survival (PFS), overall survival (OS), and molecular correlative studies. Results: Sixty patients were enrolled, and median follow-up for living patients is 13.8 months. Of these, 23 (38%) received SBRT+nivolumab+urelumab and 37 (62%) received SBRT+nivolumab+cabiralizumab. Seven patients (12%) experienced a DLT ( n = 3 grade 3, n = 4 grade 4) in the following anatomic cohorts: abdominal/pelvic (3/17, 18%), liver (1/13, 8%), central lung (2/14, 14%), and peripheral lung (1/12, 8%). Of 41 patients radiographically evaluable for best overall response including 55 radiated and 23 unirradiated RECIST target lesions, 2 had complete responses (5%), 7 had partial responses (17%), 12 had stable disease (29%), and 20 had progression (49%). Median estimated PFS and OS are 3.0 months [95% confidence interval (CI), 2.9-4.8] and 17.0 months (95% CI, 6.8-undetermined), respectively. No patients with elevated pre-SBRT serum IL8 experienced a response. Conclusions: SBRT to ≤4 sites with nivolumab+urelumab or nivolumab+cabiralizumab for treating advanced solid tumors is feasible with acceptable toxicity and modest antitumor activity. See related commentary by Rodriguez-Ruiz et al., p. 5443 . (©2021 American Association for Cancer Research.) |
| التعليقات: | Comment in: Clin Cancer Res. 2021 Oct 15;27(20):5443-5445. (PMID: 34344796) |
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| المشرفين على المادة: | 0 (Antibodies, Monoclonal) 31YO63LBSN (Nivolumab) 230902QLLC (urelumab) 0 (cabiralizumab) |
| تواريخ الأحداث: | Date Created: 20210625 Date Completed: 20220402 Latest Revision: 20240229 |
| رمز التحديث: | 20240229 |
| DOI: | 10.1158/1078-0432.CCR-21-0810 |
| PMID: | 34168049 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1557-3265 |
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| DOI: | 10.1158/1078-0432.CCR-21-0810 |