Atezolizumab in combination with neoadjuvant chemotherapy and interval cytoreductive surgery for patients with newly diagnosed advanced-stage epithelial ovarian cancer: the AdORN study

OBJECTIVE: Evaluate safety, efficacy, and response markers to atezolizumab, an immune checkpoint inhibitor, when combined with neoadjuvant chemotherapy (NACT) for primary epithelial ovarian, tubal, and peritoneal cancer (EOC). METHODS: Eligible patients had high-grade stage III/IV EOC planned for NACT and interval cytoreductive surgery (ICS). After pretreatment biopsy, patients receivedweekly paclitaxel (80 mg/m2) with carboplatin (AUC6) and atezolizumab (1200mg) every 3 weeks for 3 cycles before ICS, and 3 cycles +/- bevacizumab post-ICS, followed by maintenance atezolizumab +/- bevacizumab or a PARPinhibitor. The primary endpoint was frequency of delay in ICS due to atezolizumab-related toxicities. Frequency/severity of adverse events (AE), response prior to ICS, and immune translational parameters were assessed. RESULTS: Negative results of IMagyn050 led to early termination; 18 of 40 planned patients enrolled: median age 69 years (range 46-87); majority were white (78%), had Stage III disease (72%), high-grade serous histology (100%), and no BRCAmutation (72%). Fifteen patients underwent ICS; 3 stopped protocol therapy prior to cycle 3 for non-atezolizumab-related reasons. Thromboembolism led to delay of ICS in one patient. Optimal cytoreduction was achieved in 13 (86%) patients. Treatment-related AEs were as expected. Partial response occurred in 9 (60%) and stable disease in 6 (40%). Patients with response versus stable disease had elevated post-treatment CXCL10, TNFα, and IL10. Immune compartments showed increased inflammatory markers, while tumor showed increased inflammatory and suppressive markers. CONCLUSIONS: NACT with atezolizumab was feasible and did not delay ICS. Translational parameters showed heterogeneous changes reflecting both immune activation and adaptive immune resistance.