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06. Ovarian cancer
562 Benefit from atezolizumab in patients with a poor prognostic ovarian cancer in first-line setting: IMAGYN-050 trial
  1. Benoit You1,
  2. Charles Anderson2,
  3. Sabrina Chiara Cecere3,
  4. Aurore Carrot4,
  5. Tashanna Myers5,
  6. Florian Heitz6,
  7. Sharma Sudarshan7,
  8. Fatih Selçukbiricik8,
  9. Carol Aghajanian9,
  10. Josefin Fernebro10,
  11. Stephanie Blank11,
  12. Maria Elena Laudani12,
  13. Premal Thaker13,
  14. Mayu Yunokawa14,
  15. Lynday willmott15,
  16. Yvette He16,
  17. Charles Landen17,
  18. Yvonne G Lin18,
  19. Jesús alarcón19 and
  20. Kathleen N Moore20
  1. 1Lyon University Hospital, IC-HCL, CICLY, Lyon University, GINECO, Lyon, France
  2. 2Division of Gynecologic Oncology, University of Colorado Health Sciences Center, Campus Box B198–4, 12631 E 17th Ave, PO Box 6511, Aurora, USA
  3. 3Pascale National Cancer Institute Foundation (IRCCS), Napoli, Italy
  4. 4Lyon University, Lyon, France
  5. 5Baystate Mary Lane HospitalWare, Massachussets, USA
  6. 6AGO Study Group and Ev. Kliniken Essen-Mitte, Essen, Germany
  7. 7Baystate Mary Lane HospitalWare, Massachusetts, USA
  8. 8Koç University Hospital, Koç University School of Medicine Department of Medical Oncology, Istanbul, Turkey
  9. 9Memorial Sloan Kettering Cancer, New York, USA
  10. 10Karolinska University Hospital, Stockholm, Sweden
  11. 11Icahn School of Medicine at Mount Sinai, New York, USA
  12. 12Department of Surgical Sciences, University of Turin, Torino, Italy
  13. 13Washington University School of Medicine, Saint Louis, USA
  14. 14Japanese Foundation for Cancer Research, Cancer Institute Hospital of JFCR, Tokyo, Japan
  15. 15Abrazo Central Campus, Phoenix, USA
  16. 16Parexel, Chengdu, China
  17. 17Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham, USA
  18. 18Genentech-Roche, San Francisco, USA
  19. 19Hospital Son Espases, Palma De Mallorca, Spain
  20. 20University of Oklahoma Health Sciences Center, Oklahoma City, USA

Abstract

Introduction/Background Adding the anti-PD-L1 immune-checkpoint-inhibitor (ICI), atezolizumab, to first-line chemotherapy + bevacizumab did not improve PFS for unselected ovarian cancer (OC) patients in IMAGYN-050 phase III trial. In the GCIG meta-analysis, the patients with a poorly chemosensitive disease (unfavorable KELIM score <1.0) that was not amenable to optimal surgery had a very poor survival. We hypothesized that KELIM may help identify a particularly poor prognostic patient subgroup deriving a PFS benefit from treatment intensification with the ICI atezolizumab.

Methodology This post-hoc analysis was performed on 1,199 participants treated with atezolizumab (n=597) or placebo (n=602) with ≥3 CA125 measurements. Independent prognostic factors were identified using univariate/multivariate analyses among following covariates: Disease stage (III/IV); Pathological subtype; ECOG performance-status; Chemotherapy-setting (neo-adjuvant/adjuvant); Surgery outcome (optimal/sub-optimal resection); PDL-1 expression (positive/negative); BRCA mutation (mutated/wild-type); and KELIM score (unfavorable<1.0/favorable≥1.0). The PFS benefit from atezolizumab addition (vs.placebo) was tested in patients with both an unfavorable KELIM score<1.0 and a sub-optimal surgery (once validated as independent prognostic factors).

Results Univariate and multivariate analyses confirmed that both KELIM score (favorable/unfavorable, HR=0.61, 95%CI 0.54–0.69) and surgery outcome (sub-optimal/optimal, HR=1.41, 95%CI 1.19–1.67) were independently associated with PFS. Adding atezolizumab to frontline regimen was associated with longer PFS in the poor prognosis subgroup (n=269) characterized by both an unfavorable KELIM score and sub-optimal cytoreduction (median PFS: 14.3 vs 11.3 months, HR=0.75, 95%CI 0.59–0.95, P=0.02), and consistent in both neo-adjuvant/adjuvant settings. No significant PFS benefit was observed from atezolizumab with KELIM score assessed alone, or among the other prognostic subgroups.

Conclusion In IMAGYN-50 trial, the poor prognostic subgroup of ovarian cancer patients (unfavorable KELIM score <1.0 and sub-optimal surgery), might have derived a significant PFS benefit from the treatment intensification with the ICI atezolizumab. These outcomes on the largest phase III trial dataset open new perspectives about the best population for immunotherapy addition.

Disclosures BY: Consulting for MSD, Astra-Zeneca, GSK-TESARO, BAYER, Roche-Genentech, ECS Progastrine, Novartis, LEK, Amgen, Clovis Oncology, Merck Serono, BMS, SEAGEN, Myriad, Menarini, Gilead, EISAI.

PT: Grants or consulting: GSK, Merck, UpToDate, Versastem, Caris, AZ, Clovis, ZEntalis, Immunogen, Addi Biopharma, Seagen, Immunon. Stock holder: Immunon

CA: Clinical trial funding to institution (MSK): Abbvie – MSK PI, GOG3005; Astra Zeneca - MSK PI, SOLO1/GOG 3004; National Coordinating Investigator & MSK PI, D081RC00001; ENGOT-ov46; AGO-OVAR 23; GOG-3025; Clovis – MSK PI, ARIEL 2 & 3; Genentech/Roche – MSK PI, GOG3015 (IMagyn050). Consulting: Blueprint Medicine – Advisory Board 6/30/21 (no consulting fee); Merck - Global Cervical and Ovarian Cancer Virtual Advisory Board 7/10/23; AstraZeneca - AZ eVOLVE DMC 4/26/23-ongoing

JF: Educational activities, GSK and Astra Zeneca

TM: Immunogen

YGL is employed by Roche-Genentech and stock shareholder

YH was employed by Roche-Genentech

All other coauthors disclose no conflict of interest.

https://doi.org/10.1136/ijgc-2024-ESGO.46

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