A single-arm, phase II study of niraparib and bevacizumab maintenance therapy in platinum-sensitive, recurrent ovarian cancer patients previously treated with a PARP inhibitor: Korean Gynecologic Oncology Group (KGOG 3056)/ NIRVANA-R trial

다국어 초록 (Multilingual Abstract)

Background: Given the expanding clinical use of poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitors (PARPis), there is a significant need for optimal strategies with which to treat patients whose cancer progresses while using a PARPi. However, the treatment consensus after PARPi has not been established. The aim of the Korean Gynecologic Oncology Group (KGOG) 3056/NIRVANA-R trial is to investigate the efficacy of niraparib in combination with bevacizumab as a maintenance therapy in platinum-sensitive ovarian cancer patients who were previously treated with a PARPi.
Methods: The KGOG 3056/NIRVANA-R is a multi-centre, investigator-initiated, single-arm, phase II trial of patients with platinum-sensitive recurrent ovarian cancer recruited from seven KGOG sites. This study included patients with platinum-sensitive recurrent epithelial ovarian cancer who received at least 2 previous courses of platinum-containing therapy and had been treated with a PARPi. Mucinous histology type was excluded. Patients who had responded to the last platinum regimen (either complete or partial response) were eligible to participate in this study. Forty-four patients will be recruited. All enrolled patients are treated with niraparib and bevacizumab for maintenance therapy until disease progression,1/8KGOG 3046/NIRVANA-Runacceptable toxicity, or withdrawal of patient consent. The primary endpoint of the study is 6-month progression-free survival rate. Accrual is expected to be completed in 2022, followed by presentation of results in 2023.
Trial Registration: ClinicalTrials.gov Identifier: NCT04734665

참고문헌 (Reference)

1 Coleman RL, "Veliparib with first-line chemotherapy and as maintenance therapy in ovarian cancer" 381 : 2403-2415, 2019

2 Kondrashova O, "Secondary somatic mutations restoring RAD51C and RAD51D associated with acquired resistance to the PARP inhibitor rucaparib in high-grade ovarian carcinoma" 7 : 984-998, 2017

3 Coleman RL, "Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy(ARIEL3) : a randomised, double-blind, placebo-controlled, phase 3 trial" 390 : 1949-1961, 2017

4 Noordermeer SM, "PARP inhibitor resistance : a tug-of-war in BRCA-mutated cells" 29 : 820-834, 2019

5 Pujade-Lauraine E, "Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation(SOLO2/ENGOT-Ov21) : a double-blind, randomised, placebo-controlled, phase 3 trial" 18 : 1274-1284, 2017

6 Ray-Coquard I, "Olaparib plus bevacizumab as first-line maintenance in ovarian cancer" 381 : 2416-2428, 2019

7 Pujade-Lauraine E, "OReO/ENGOT Ov-38 : a phase IIIb trial of olaparib maintenance retreatment in patients with epithelial ovarian cancer" 28 : v351-v352, 2017

8 Mirza MR, "Niraparib plus bevacizumab versus niraparib alone for platinum-sensitive recurrent ovarian cancer(NSGO-AVANOVA2/ENGOT-ov24) : a randomised, phase 2, superiority trial" 20 : 1409-1419, 2019

9 Mirza MR, "Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer" 375 : 2154-2164, 2016

10 González-Martín A, "Niraparib in patients with newly diagnosed advanced ovarian cancer" 381 : 2391-2402, 2019

11 Liao H, "Mechanisms for stalled replication fork stabilization : new targets for synthetic lethality strategies in cancer treatments" 19 : e46263-, 2018

12 Moore K, "Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer" 379 : 2495-2505, 2018

13 Burger RA, "Incorporation of bevacizumab in the primary treatment of ovarian cancer" 365 : 2473-2483, 2011

14 Ledermann JA, "Homologous recombination deficiency and ovarian cancer" 60 : 49-58, 2016

15 Konstantinopoulos PA, "Homologous recombination deficiency : exploiting the fundamental vulnerability of ovarian cancer" 5 : 1137-1154, 2015

16 Sung H, "Global cancer statistics 2020 : GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries" 71 : 209-249, 2021

17 Lheureux S, "EVOLVE : a multicenter open-label single-arm clinical and translational phase II trial of cediranib plus olaparib for ovarian cancer after PARP inhibition progression" 26 : 4206-4215, 2020

18 Vergote I, "ENGOT-OV43/KEYLYNK-001: a phase III, randomized, double-blind, active- and placebo-controlled study of pembrolizumab plus chemotherapy with olaparib maintenance for first-line treatment of BRCA-nonmutated advanced epithelial ovarian cancer" 37 (37): TPS5603-, 2019

19 Harter P, "DUO-O: a randomized phase III trial of durvalumab (durva) in combination with chemotherapy and bevacizumab (bev), followed by maintenance durva, bev and olaparib (olap), in newly diagnosed advanced ovarian cancer patients" 37 (37): TPS5598-, 2019

20 Liu JF, "Combination cediranib and olaparib versus olaparib alone for women with recurrent platinum-sensitive ovarian cancer : a randomised phase 2 study" 15 : 1207-1214, 2014

21 Mukhopadhyay A, "Clinicopathological features of homologous recombination-deficient epithelial ovarian cancers : sensitivity to PARP inhibitors, platinum, and survival" 72 : 5675-5682, 2012

22 Kaplan AR, "Cediranib suppresses homology-directed DNA repair through down-regulation of BRCA1/2 and RAD51" 11 : eaav4508-, 2019

23 Jaspers JE, "BRCA2-deficient sarcomatoid mammary tumors exhibit multidrug resistance" 75 : 732-741, 2015

24 Monk BJ, "Anti-angiogenic agents in ovarian cancer: past, present, and future" 27 (27): i33-i39, 2016

25 Lee JY, "An umbrella study of biomarker-driven targeted therapy in patients with platinum-resistant recurrent ovarian cancer : a Korean Gynecologic Oncology Group study(KGOG 3045), AMBITION" 49 : 789-792, 2019

26 Westin SN, "Abstract CT158: ATHENA (GOG-3020/ENGOT-ov45): a randomized, double-blind, placebo-controlled, Phase III study of rucaparib + nivolumab following front-line platinum-based chemotherapy in ovarian cancer" 79 : CT158-, 2019

27 이용재 ; 임명철 ; 김병기 ; Natalie YL Ngoi ; 최철훈 ; 박상윤 ; David SP Tan ; 고윤정 ; 이정윤, "A single-arm phase II study of olaparib maintenance with pembrolizumab and bevacizumab in BRCA non-mutated patients with platinum-sensitive recurrent ovarian cancer (OPEB-01)" 대한부인종양학회 32 (32): 1-7, 2021

28 Perren TJ, "A phase 3 trial of bevacizumab in ovarian cancer" 365 : 2484-2496, 2011

29 Bunting SF, "53BP1 inhibits homologous recombination in Brca1-deficient cells by blocking resection of DNA breaks" 141 : 243-254, 2010

30 Chan N, ""Contextual"synthetic lethality and/or loss of heterozygosity : tumor hypoxia and modification of DNA repair" 16 : 4553-4560, 2010