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A Pilot Study of Atezolizumab Plus Hypofractionated Image Guided Radiation Therapy for the Treatment of Advanced Non-Small Cell Lung Cancer.
- Source :
-
International journal of radiation oncology, biology, physics [Int J Radiat Oncol Biol Phys] 2020 Sep 01; Vol. 108 (1), pp. 170-177. Date of Electronic Publication: 2019 Nov 19. - Publication Year :
- 2020
-
Abstract
- Purpose: Preclinical data and subset analyses from immunotherapy clinical trials indicate that prior radiation therapy was associated with better progression-free survival and overall survival when combined with immune checkpoint inhibitors in patients with non-small cell lung cancer. We present a prospective study of hypofractionated image guided radiation therapy (HIGRT) to a single site of metastatic disease concurrently with atezolizumab in patients with metastatic non-small cell lung cancer.<br />Methods and Materials: Patients meeting eligibility criteria received 1200 mg of atezolizumab intravenously every 3 weeks with concurrent 3- or 5-fraction HIGRT starting no later than the second cycle. The 3-fraction regimen employed a minimum of 8 Gy per fraction compared with 6 Gy for the 5-fraction regimen. Imaging was obtained every 12 weeks to assess response.<br />Results: From October 2015 to February 2017, 12 patients were enrolled in the study (median age 64; range, 55-77 years). The best response by the Response Evaluation in Solid Tumors criteria was partial response in 3 and stable disease in 3, for a disease control rate of 50%. Five patients had a grade 3 immune-related adverse event, including choreoretinitis (n = 1), pneumonitis (n = 1), transaminitis (n = 1), fatigue (n = 1), and peripheral neuropathy (n = 1). The median progression-free survival was 2.3 months, and the median overall survival was 6.9 months (range, 0.4-not reached). There was no clear association between peripheral blood T cell repertoire characteristics at baseline, PD-L1, or tumor mutations and response or outcome. One long-term survivor exhibited oligoclonal T cell populations in a baseline tumor biopsy that were consistently detected in peripheral blood over the entire course of the study.<br />Conclusions: HIGRT plus atezolizumab resulted in an overall response rate of 25% and disease control rate of 50% in this pilot study. The incidence of grade 3 adverse events was similar to that of atezolizumab alone. Alhough it was a pilot study with limited sample size, the results generated hypotheses worthy of further investigation.<br /> (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Subjects :
- Adult
Aged
Aged, 80 and over
B7-H1 Antigen metabolism
Carcinoma, Non-Small-Cell Lung diagnostic imaging
Carcinoma, Non-Small-Cell Lung pathology
Combined Modality Therapy
Female
Gene Expression Regulation, Neoplastic drug effects
Gene Expression Regulation, Neoplastic radiation effects
Humans
Lung Neoplasms diagnostic imaging
Lung Neoplasms pathology
Male
Middle Aged
Pilot Projects
Safety
Treatment Outcome
Antibodies, Monoclonal, Humanized therapeutic use
Carcinoma, Non-Small-Cell Lung drug therapy
Carcinoma, Non-Small-Cell Lung radiotherapy
Lung Neoplasms drug therapy
Lung Neoplasms radiotherapy
Radiation Dose Hypofractionation
Radiotherapy, Image-Guided
Subjects
Details
- Language :
- English
- ISSN :
- 1879-355X
- Volume :
- 108
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- International journal of radiation oncology, biology, physics
- Publication Type :
- Academic Journal
- Accession number :
- 31756415
- Full Text :
- https://doi.org/10.1016/j.ijrobp.2019.10.047