A Pilot Study of Atezolizumab Plus Hypofractionated Image Guided Radiation Therapy for the Treatment of Advanced Non-Small Cell Lung Cancer.

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.

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.

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.

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.

• Authors: Angel Qin, Ramesh Rengan, Sylvia Lee, Rafael Santana-Davila, Bernardo H L Goulart, Renato Martins, Christina Baik, Gregory P Kalemkerian, Khaled A Hassan, Bryan J Schneider, James A Hayman, Shruti Jolly, Jason Hearn, Theodore S Lawrence, Andrea M H Towlerton, Muneesh Tewari, Dafydd Thomas, Lili Zhao, Noah Brown, Timothy L Frankel, Edus H Warren, Nithya Ramnath
• Journal: International journal of radiation oncology, biology, physics (Int J Radiat Oncol Biol Phys) Vol. 108 Issue 1 Pg. 170-177 (09 01 2020) ISSN: 1879-355X [Electronic] United States
• PMID: 31756415 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Antibodies, Monoclonal, Humanized
• B7-H1 Antigen
• CD274 protein, human
• atezolizumab

Topics

• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal, Humanized (therapeutic use)
• B7-H1 Antigen (metabolism)
• Carcinoma, Non-Small-Cell Lung (diagnostic imaging, drug therapy, pathology, radiotherapy)
• Combined Modality Therapy
• Female
• Gene Expression Regulation, Neoplastic (drug effects, radiation effects)
• Humans
• Lung Neoplasms (diagnostic imaging, drug therapy, pathology, radiotherapy)
• Male
• Middle Aged
• Pilot Projects
• Radiation Dose Hypofractionation
• Radiotherapy, Image-Guided
• Safety
• Treatment Outcome