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LB005/#1605  Randomized, phase II/III study of pegylated liposomal doxorubicin, bevacizumab, and atezolizumab in platinum-resistant ovarian cancer (NRG-GY009): clinical outcomes by PD-L1 and T cell infiltration status
  1. Roisin O’Cearbhaill1,
  2. Dmitriy Zamarin2,
  3. Michael Sill3,
  4. Hoa Duong4,
  5. Steven Waggoner5,
  6. Rachel Grisham1,
  7. Floor Backes6,
  8. Robert Mannel7,
  9. Janos Tanyi8,
  10. Matthew Powell9,
  11. Cara Mathews10,
  12. Sharad Ghamande11,
  13. Leah McNally12,
  14. Alexander Olawaiye13,
  15. David Bender14,
  16. Linda Duska15,
  17. Heather Lankes16,
  18. Russell Schilder17,
  19. Michael Bookman18 and
  20. Carol Aghajanian1
  1. 1Memorial Sloan Kettering Cancer Center, Medicine, New York, NY, United States of America
  2. 2Icahn School of Medicine at Mount Sinai, New York, NY, United States of America
  3. 3NRG Oncology, Roswell Park Comprehensive Cancer Center, Dept. of Biostatistics and Bioinformatics, Buffalo, NY, United States of America
  4. 4Kaiser-Permanente Sacramento, Hematology/Oncology, Sacramento, CA, United States of America
  5. 5CWRU Case Comprehensive Cancer Center, Gynecologic Oncology, Cleveland, OH, United States of America
  6. 6Ohio State University Comprehensive Cancer Center, Gynecologic Oncology, Ohio, OH, United States of America
  7. 7University of Oklahoma Health Sciences Center, Obstetrics and Gynecology, Oklahoma, OK, United States of America
  8. 8University of Pennsylvania/Abramson Cancer Center, Obstetrics and Gynecology, Philadelphia, PA, United States of America
  9. 9Washington University, Gynecologic Oncology, St Louis, MO, United States of America
  10. 10Women & Infants Hospital, Providence, RI, United States of America
  11. 11Medical College of Georgia, Obstetrics and Gynecology, Augusta, GA, United States of America
  12. 12Duke Cancer Institute, Gynecologic Oncology, Durham, NC, United States of America
  13. 13University of Pittsburgh Medical Center, Pittsburgh, PA, United States of America
  14. 14University of Iowa, Obstetrics and Gynecology, Iowa City, IA, United States of America
  15. 15UVA School of Medicine, Charlottesville, VA, United States of America
  16. 16NRG Oncology Operations Center-Philadelphia East, Philadelphia, PA, and Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, The Ohio State University Wexner Medical Center, Columbus, OH, United States of America
  17. 17Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, United States of America
  18. 18Kaiser Permanente Northern California, San Francisco, CA, United States of America

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.

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