Academic Journal
Biomarker-guided targeted therapy in platinum-resistant ovarian cancer (AMBITION; KGOG 3045): a multicentre, open-label, five-arm, uncontrolled, umbrella trial
| العنوان: | Biomarker-guided targeted therapy in platinum-resistant ovarian cancer (AMBITION; KGOG 3045): a multicentre, open-label, five-arm, uncontrolled, umbrella trial |
|---|---|
| المساهمون: | Jung-Yun Lee, Byoung-Gie Kim, Jae-Weon Kim, Jung Bok Lee, Eunhyang Park, Je-Gun Joung, Sunghoon Kim, Chel Hun Choi, Hee Seung Kim, Kim, Sung Hoon |
| بيانات النشر: | Taehan Puin Chongyang Hakhoe |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Antineoplastic Combined Chemotherapy Protocols / therapeutic use, B7-H1 Antigen* / therapeutic use, Biomarkers, Carcinoma, Ovarian Epithelial / drug therapy, Drug Resistance, Neoplasm, Female, Humans, Ovarian Neoplasms* / pathology, Paclitaxel, Topotecan / adverse effects, Biomarker, Immunotherapy, Molecular Targeted Therapy, Ovarian Cancer, Platinum Resistant |
| الوصف: | Objective: Management of heavily pre-treated platinum-resistant ovarian cancer remains a therapeutic challenge. Outcomes are poor with non-platinum, single-agent chemotherapy (CT); however, molecularly targeted anticancer therapies provide new options. Methods: This open-label, investigator-initiated, phase 2 umbrella trial (NCT03699449) enrolled patients with platinum-resistant ovarian cancer (at least 2 prior lines of CT and Eastern Cooperative Oncology Group 0/1) to receive combination therapy based on homologous recombination deficiency (HRD) and programmed death ligand 1 (PD-L1) status determined by archival tumour sample assessment. HRD-positive patients were randomised to either olaparib 200mg bid tablet + cediranib 30mg qd (arm 1) or olaparib 300mg bid tablet + durvalumab 1,500mg q4w (arm 2). HRD-negative patients were allocated to either durvalumab 1,500 mg q4w + pegylated liposomal doxorubicin (PLD) or topotecan or weekly paclitaxel (6 cycles; arm 3, those with PD-L1 expression) or durvalumab 1,500 mg q4w + tremelimumab 75mg q4w (4 doses) + PLD or topotecan or weekly paclitaxel (4 cycles; arm 4, those without PD-L1 expression). Arm 5 (durvalumab 1,500 mg q4w + tremelimumab 300mg [1 dose] + weekly paclitaxel [60 mg/m² D1,8,15 q4w for 4 cycles] was initiated after arm 4 completed. The primary endpoint was objective response rate (ORR; Response Evaluation Criteria in Solid Tumours 1.1). Results: Between Dec 2018 and Oct 2020, 70 patients (median 57 years; median 3 prior treatment lines [range 2-10]) were treated (n=16, 14, 5, 18, and 17, respectively). Overall ORR was 37.1% (26/70, 95% confidence interval=25.9, 49.5); 2 achieved complete response. ORR was 50%, 42.9%, 20%, 33.3%, and 29.4%, respectively. Grade 3/4 treatment-related adverse events (TRAEs) were reported in 37.5%, 35.7%, 20%, 66.7%, and 35.3% of patients, respectively. No TRAEs leading to treatment discontinuation and no grade 5 TRAEs were observed. Conclusion: This study, the first biomarker-driven umbrella trial in platinum-resistant ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 2005-0380 2005-0399 |
| Relation: | JOURNAL OF GYNECOLOGIC ONCOLOGY; J01428; OAK-2022-06706; OAK-2022-06707; OAK-2022-06708; https://ir.ymlib.yonsei.ac.kr/handle/22282913/191687; T202205067; JOURNAL OF GYNECOLOGIC ONCOLOGY, Vol.33(4) : e45, 2022-07 |
| DOI: | 10.3802/jgo.2022.33.e45 |
| الاتاحة: | https://ir.ymlib.yonsei.ac.kr/handle/22282913/191687 https://doi.org/10.3802/jgo.2022.33.e45 |
| Rights: | CC BY-NC-ND 2.0 KR |
| رقم الانضمام: | edsbas.1F094B25 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 20050380 20050399 |
|---|---|
| DOI: | 10.3802/jgo.2022.33.e45 |