Evaluation of Blood Tumor Mutation Burden for the Efficacy of Second-Line Atezolizumab Treatment in Non-Small Cell Lung Cancer: BUDDY Trial

Cheol-Kyu Park; Ha Ra Jun; Hyung-Joo Oh; Ji-Young Lee; Hyun-Ju Cho; Young-Chul Kim; Jeong Eun Lee; Seong Hoon Yoon; Chang Min Choi; Jae Cheol Lee; Sung Yong Lee; Shin Yup Lee; Sung-Min Chun; In-Jae Oh

doi:10.3390/cells12091246

Evaluation of Blood Tumor Mutation Burden for the Efficacy of Second-Line Atezolizumab Treatment in Non-Small Cell Lung Cancer: BUDDY Trial

Cells. 2023 Apr 25;12(9):1246. doi: 10.3390/cells12091246.

Authors

Affiliations

¹ Department of Internal Medicine, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Gwangju 58128, Republic of Korea.
² Department of Medical Science, Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea.
³ Department of Internal Medicine, Chungnam National University Hospital, Daejeon 35015, Republic of Korea.
⁴ Department of Internal Medicine, Pusan National University Yangsan Hospital, Pusan 50612, Republic of Korea.
⁵ Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea.
⁶ Department of Internal Medicine, Korea University Guro Hospital, Seoul 08308, Republic of Korea.
⁷ Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea.
⁸ Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea.

Abstract

This study aimed to investigate the feasibility of blood-based biomarkers, including blood tumor mutation burden (bTMB), to predict atezolizumab efficacy in relapsed and advanced non-small cell lung cancer (NSCLC). Stage IV NSCLC patients who had previously received platinum-doublet chemotherapy were recruited and received 1200 mg of atezolizumab every three weeks. Blood was collected to obtain plasma cell-free DNA (cfDNA) before the first cycle (C0) and at the fourth cycle (C4). bTMB was measured by CT-ULTRA in patients with cfDNA over 10 ng. The objective response rate (ORR) of the enrolled 100 patients was 10%, and there was no difference in ORR according to bTMB (cutoff: 11.5 muts/Mb) at C0 (high bTMB: 8.1% vs. low bTMB: 11.1%). However, the C4/C0 bTMB ratio was significantly lower in the durable clinical benefit (DCB) patients. The cfDNA concentration at C0, the C4/C0 ratio of the cfDNA concentration, the highest variant allele frequency (hVAF), and the VAF standard deviation (VAFSD) were significantly lower in the DCB patients. In the multivariate analysis, a high cfDNA concentration at C0 (cutoff: 8.6 ng/mL) and a C4/C0 bTMB ratio greater than 1 were significantly associated with progression-free survival. These results suggest that baseline levels and dynamic changes of blood-based biomarkers (bTMB, cfDNA concentration, and VAFSD) could predict atezolizumab efficacy in previously treated NSCLC patients.

Keywords: atezolizumab; blood tumor mutation burden; cell-free DNA; non-small cell lung cancer.

Publication types

Clinical Trial
Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers, Tumor / genetics
Biomarkers, Tumor / metabolism
Carcinoma, Non-Small-Cell Lung* / drug therapy
Carcinoma, Non-Small-Cell Lung* / genetics
Carcinoma, Non-Small-Cell Lung* / pathology
Cell-Free Nucleic Acids*
Humans
Lung Neoplasms* / drug therapy
Lung Neoplasms* / genetics
Lung Neoplasms* / pathology
Mutation / genetics

Substances

atezolizumab
Biomarkers, Tumor
Cell-Free Nucleic Acids

Grants and funding

This research was funded by Roche, Korea (ML40993), and the National Research Foundation of Korea grant funded by the Korean government (NRF-2017M3A9G5061671 to Sung-Min Chun, NRF-2019M3E5D1A02067951 to Cheol-Kyu Park, and NRF-2020R1A5A2031185 to In-Jae Oh). The funder had no role in the study design, data collection, analysis, decision to publish or preparation of the manuscript.