Abstract 1085P
Background
We aimed to investigate the feasibility of using blood tumor mutation burden (bTMB) as a biomarker of atezolizumab, anti-programmed death-ligand 1 (PD-L1) inhibitor, efficacy in previously treated patients with relapsed/advanced non-small cell lung cancer (NSCLC).
Methods
We prospectively recruited patients diagnosed with relapsed/advanced NSCLC who had received one or two previous platinum-based combination chemotherapy. Patients received atezolizumab 1200 mg every 3 weeks. Blood was collected to obtain plasma cell-free DNA (cfDNA) before the first cycle (C0) and at the fourth cycle (C4) or end-of-treatment (EOT) visit. The measurement of bTMB was performed in patients with cfDNA >10 ng amount using CT-ULTRA, a targeted NGS panel specifically designed for ctDNA analysis. The primary endpoint was to evaluate objective response rate (ORR) in bTMB-high (bTMBhi) and -low (bTMBlo) population.
Results
Between December 2019 and April 2021, 100 patients were enrolled. bTMB was measured in cfDNA of 89 samples at C0 and paired 64 samples at C4/EOT. ORR was 10% and there was no difference in ORR according to bTMB (cutoff: 7.7 muts/Mb) at C0 (bTMBhi 9.3% vs. bTMBlo 11.4%; p=0.734). At a median follow-up of 12.3 months, the median PFS was 2.1 months. Patients with high PD-L1 (≥50%), low cfDNA at C0 (cutoff: 8.6 ng/mL) or decreased bTMB from C0 to C4/EOT showed significant PFS benefit (p<0.05), and the median PFS was significantly different between patients with high PD-L1/bTMBhi and with low or negative PD-L1/bTMBlo (not reached vs. 2.0; hazard ratio [HR] 3.32, p=0.015). In multivariable analysis, EGFR mutation (HR 2.92, p=0.029) and increased bTMB from C0 to C4/EOT (HR 2.97, p=0.047) were the significant risk factors for PFS.
Conclusions
In previously treated NSCLC patients, improvement in treatment efficacy of atezolizumab was correlated with high PD-L1 expression and serial decrease in bTMB after treatment, suggesting that PD-L1 expression combined with bTMB could be predictive for atezolizumab benefit.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Roche.
Disclosure
All authors have declared no conflicts of interest.