Article Text
Abstract
Introduction NRG-GY009 was a randomized clinical trial of pegylated liposomal doxorubicin (PLD), bevacizumab (BEV), and atezolizumab (ATEZO) and PLD/ATEZO compared to PLD/BEV in patients with platinum-resistant ovarian cancer (PROC) (n=444). Addition of ATEZO to PLD/BEV did not result in a statistically significant prolongation of progression-free survival or overall survival (OS). Here, we present interaction/subgroup analyses by baseline tumor PD-L1 expression and tumor infiltrating lymphocyte (TIL) status.
Methods Archival tumor samples were analyzed for immune cell PD-L1 and CD8 infiltration using Ventana SP142 and CD8 IHC assays, respectively. Outcomes were examined by PD-L1 status using 5% or 1% as cutoffs, CD8 status using quartiles, and TIL status using tertiles. Log-rank and Cox models were used to assess the relationships between the individual biomarkers and PFS/OS.
Results Baseline tissue was analyzed from PLD/BEV/ATEZO (n=131), PLD/ATEZO (n=105), and PLD/BEV (n=134) patients, yielding PD-L1≥5% and PD-L1≥1% in 45 and 169 patients, respectively. Patients in the PD-L1<1% group who received PLD/BEV/ATEZO exhibited prolonged PFS (HR 0.55, 95% CI 0.391-0.784) and OS (HR 0.66, 95% CI 0.458-0.940) when compared to PLD/BEV. No significant differences were noted between the treatment arms in the PD-L1≥1% group. When examining CD8+ T cell TIL status, no significant associations were observed between the presence of immune cells and clinical outcomes.
Conclusion/Implications In this exploratory analysis, patients with PD-L1<1% tumors demonstrated improved PFS/OS when treated with PLD/BEV/ATEZO when compared to PLD/BEV, highlighting the unreliability of PD-L1 as a biomarker in PROC. Identification of immune biomarkers relevant to PROC remains an unmet need.