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정제균Je-Gun Joung
차의과학대학교
Clin. Cancer Res., Mar 05 2025, | https://doi.org/10.1158/1078-0432.CCR-24-3753
Neoadjuvant Chemotherapy with Dual Immune Checkpoint Inhibitors for Advanced-Stage Ovarian Cancer: Final Analysis of TRU-D Phase II Nonrandomized Clinical Trial
Junsik Park1, a,Je-Gun Joung2, a, Myong Cheol Lim3, Jungbok Lee4, Byoung-Gie Kim5, Jae-Weon Kim6, So Jin Shin7, Sunghoon Kim8, Eunhyang Park9, Chel Hun Choi5, Hee Seung Kim6, Sang Yoon Park3, and Jung-Yun Lee8, *
1Department of Obstetrics and Gynecology, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, South Korea
2Department of Biomedical Science, College of Life Science, CHA University, Seongnam, South Korea
3Center for Gynecologic Cancer, National Cancer Center, Goyang, South Korea
4Department of Clinical Epidemiology and Biostatistics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
5Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea
6Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, South Korea
7Department of Obstetrics and Gynecology, Keimyung University Dongsan Medical Center, Daegu, South Korea
8Department of Obstetrics and Gynecology, Yonsei University College of Medicine, Seoul, South Korea
9Department of Pathology, Yonsei University College of Medicine, Seoul, South Korea
aThese authors contributed equally as first authors.
*Corresponding author: Jung-Yun Lee, MD, PhD
1Department of Obstetrics and Gynecology, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, South Korea
2Department of Biomedical Science, College of Life Science, CHA University, Seongnam, South Korea
3Center for Gynecologic Cancer, National Cancer Center, Goyang, South Korea
4Department of Clinical Epidemiology and Biostatistics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
5Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea
6Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, South Korea
7Department of Obstetrics and Gynecology, Keimyung University Dongsan Medical Center, Daegu, South Korea
8Department of Obstetrics and Gynecology, Yonsei University College of Medicine, Seoul, South Korea
9Department of Pathology, Yonsei University College of Medicine, Seoul, South Korea
aThese authors contributed equally as first authors.
*Corresponding author: Jung-Yun Lee, MD, PhD
Abstract
Purpose: This open-label, investigator-initiated, phase II study was conducted to evaluate the safety, survival and neoadjuvant outcomes of NAC combined with dual immune checkpoint inhibitors in advanced-stage EOC.
Patients and methods: Between June 2019 and July 2021, 45 patients with unresectable stage III-IV EOC were enrolled. The patients received three cycles of NAC combined with durvalumab and tremelimumab. All patients underwent interval debulking surgery and received three cycles of durvalumab and adjuvant chemotherapy, followed by 12 cycles of durvalumab as maintenance therapy. The primary endpoint was the 12-month progression-free survival (PFS) rate; the secondary endpoints were the objective response rate (ORR) after NAC, a chemotherapy response score (CRS), pathologic complete response (pCR), overall survival (OS), and safety. The pre-planned exploratory analyses assessed the lymphocyte infiltration, PD-L1 expression, and genomic profiles of pre-treatment tumors.
Results: The 12-month PFS rate was 65.9% (95% CI, 52.8-NE), while the 24- and 30-month PFS rates were 38.6% (95% CI, 26.7-NE) and 36.4% (95% CI, 24.7-NE), respectively. After NAC, the ORR was 86.7%, while 14 patients (31.1%) had a CRS 3, and five (11.1%) achieved pCR. The 30-month OS rate was 87.7%. The most common grade ≥ 3 adverse events was neutropenia (26.7%). In an exploratory analysis, patients with pre-NAC tumors showing PD-L1 (CPS) ≥1, high Mutation Signature 3, and a high extracellular matrix signature demonstrated improved PFS outcomes.
Conclusions: NAC combined with dual immune checkpoint inhibitors is feasible for advanced-stage EOC and shows promising activity with a durable clinical response.
Patients and methods: Between June 2019 and July 2021, 45 patients with unresectable stage III-IV EOC were enrolled. The patients received three cycles of NAC combined with durvalumab and tremelimumab. All patients underwent interval debulking surgery and received three cycles of durvalumab and adjuvant chemotherapy, followed by 12 cycles of durvalumab as maintenance therapy. The primary endpoint was the 12-month progression-free survival (PFS) rate; the secondary endpoints were the objective response rate (ORR) after NAC, a chemotherapy response score (CRS), pathologic complete response (pCR), overall survival (OS), and safety. The pre-planned exploratory analyses assessed the lymphocyte infiltration, PD-L1 expression, and genomic profiles of pre-treatment tumors.
Results: The 12-month PFS rate was 65.9% (95% CI, 52.8-NE), while the 24- and 30-month PFS rates were 38.6% (95% CI, 26.7-NE) and 36.4% (95% CI, 24.7-NE), respectively. After NAC, the ORR was 86.7%, while 14 patients (31.1%) had a CRS 3, and five (11.1%) achieved pCR. The 30-month OS rate was 87.7%. The most common grade ≥ 3 adverse events was neutropenia (26.7%). In an exploratory analysis, patients with pre-NAC tumors showing PD-L1 (CPS) ≥1, high Mutation Signature 3, and a high extracellular matrix signature demonstrated improved PFS outcomes.
Conclusions: NAC combined with dual immune checkpoint inhibitors is feasible for advanced-stage EOC and shows promising activity with a durable clinical response.
논문정보
- Research article
- 2025년 03월 (BRIC 등록일 2025-03-19)
- 국내 연구진
- 의약학 > 응용의학
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