A biomarker study of atezolizumab (atezo) + bevacizumab (bev) + carboplatin (carbo) + paclitaxel (pac) (ABCP) for patients with NSCLC harboring EGFR mutations (EGFRm) after failure of TKI therapy: NEJ043.

Abstract

9079 Background: EGFRm NSCLC patients (pts) have limited treatment options after EGFR-TKI failure. We previously showed that the NEJ043 study investigating ABCP in EGFRm NSCLC pts after EGFR-TKI failure had a clinically meaningful efficacy (Furuya et al, ASCO 2022). Here we report the results of the biomarker study of NEJ043. Methods: NEJ043 study is a phase II study to evaluate the efficacy of ABCP in sensitizing EGFRm nonsquamous NSCLC pts after TKI failure. Pts received atezo (1200 mg), bev (15 mg/kg), carbo (AUC 6 mg/mL/min), and pac (175 mg/m2) every 3 weeks up to 4 cycles followed by atezo plus bev until loss of clinical benefit. Before treatment initiation and three cycles of ABCP, peripheral blood mononuclear cells (PBMCs) were collected, and immunophenotypic data at each time point was obtained by flow cytometry. Results: 60 pts were included in the NEJ043 study and PBMCs were obtained from 31 pts. Pts with a higher percentage of CD11b+DRlowCD3-CD14+ myeloid-derived suppressor cells (MDSCs) before ABCP had significantly longer PFS (median, 9.7 months (95% CI, 5.3-17.7) vs 5.6 months (95% CI, 3.9-8.1); HR 0.38; P = 0.0313). Further analysis of the immune cell phenotypes that changed between pre-treatment and the third course showed that pts with increased CD62LlowCD8+ cells (median, 12.8 months (95% CI, 5.6-20.3) vs 5.7 months (95% CI, 4.4-8.1); HR 0.25; P = 0.003) and PD-1+CCR7-CD45RA-CD8+ cells (median, 8.5 months (95% CI, 5.6-13.8) vs 5.7 months (95% CI, 2.6-8.1); HR 0.37; P = 0.0324) had significantly longer PFS. Conclusions: Inhibition of MDSCs by ABCP, especially bev, may be important for EGFRm pts whose antitumor immunity is suppressed by MDSCs before treatment. Better PFS may be expected in pts in whom ABCP therapy induced CD62LlowCD8+ effector T cells and PD-1+CCR7-CD45RA-CD8+ effector memory T cells. Clinical trial information: jRCTs031190066 .