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Time-Trend Analysis and Risk Factors for Niraparib-Induced Nausea and Vomiting in Ovarian Cancer: A Prospective Study
Young Wook Jeong, Dongkyu Eugene Kim, Ji Hyun Kim, Se Ik Kim, Hyeong In Ha, Sang-Yoon Park, Myong Cheol Lim
Received September 14, 2024  Accepted November 2, 2024  Published online November 4, 2024  
DOI: https://doi.org/10.4143/crt.2024.899    [Accepted]
AbstractAbstract PDF
Purpose
Nausea and vomiting are major non-hematological adverse events associated with niraparib maintenance therapy. This study aimed to investigate the time-trend patterns of niraparib-induced nausea and vomiting (NINV) and the associated risk factors in patients with ovarian cancer.
Materials and Methods
In this prospective study, we enrolled patients with stage III–IV epithelial ovarian cancer who received niraparib as frontline maintenance therapy. The clinicopathological characteristics and time-trend patterns of patients with NINV were collected through in-person surveys and electronic medical records from the National Cancer Center.
Results
Of 53 patients, 50 (94.3%) were diagnosed with high-grade serous ovarian carcinoma. BRCA mutations and homologous recombination deficiency (HRD) were identified in 23 (43.4%) and 32 (60.4%) patients, respectively. Thirty-one patients (58.5%) had NINV. Time-trend analyses revealed that the first peak intensity of NINV was reached at 3 h post-dose, and the second peak intensity was reached at 11 h post-dose. NINV significantly decreased from week 1 to weeks 8 and 12. In multivariate analyses of risk factors for NINV, HRD-positive tumors (p<0.001) and prior experience of chemotherapy-induced nausea and vomiting (p=0.004) were associated with the occurrence of NINV.
Conclusion
Pre-emptive treatment with antiemetics are required to manage early-phase NINV during niraparib maintenance therapy in patients with risk factors. Additional larger studies are needed to confirm these findings and to develop optimal preventive strategies for NINV.
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Breast Cancer
Talazoparib Versus Chemotherapy in Patients with HER2-negative Advanced Breast Cancer and a Germline BRCA1/2 Mutation Enrolled in Asian Countries: Exploratory Subgroup Analysis of the Phase III EMBRACA Trial
Kyung-Hun Lee, Joohyuk Sohn, Annabel Goodwin, Tiziana Usari, Silvana Lanzalone, Seock-Ah Im, Sung-Bae Kim
Cancer Res Treat. 2021;53(4):1084-1095.   Published online March 24, 2021
DOI: https://doi.org/10.4143/crt.2020.1381
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
We evaluated study outcomes in patients enrolled in Asian regions in the phase III EMBRACA trial of talazoparib vs. chemotherapy.
Materials and Methods
Patients with human epidermal growth factor receptor 2–negative germline BRCA1/2-mutated advanced breast cancer who received prior chemotherapy were randomized 2:1 to talazoparib 1 mg/day or chemotherapy (physician’s choice). Primary endpoint was progression-free survival (PFS) per independent central review in the intent-to-treat (ITT) population. This post-hoc analysis evaluated efficacy/safety endpoints in the ITT population of patients enrolled in Asian regions.
Results
Thirty-three patients were enrolled at Asian sites (talazoparib, n=23; chemotherapy, n=10). Baseline characteristics were generally comparable with the overall EMBRACA population. In Asian patients, median PFS was 9.0 months (95% confidence interval [CI] 3.0, 15.2) for talazoparib and 7.1 months (95% CI, 1.2, not reached) for chemotherapy (hazard ratio [HR] 0.74 [95% CI, 0.22, 2.44]). Objective response rate was numerically higher for talazoparib vs. chemotherapy (62.5% [95% CI, 35.4, 84.8] vs. 25.0% [95% CI, 3.2, 65.1]). Median overall survival was 20.7 months (95% CI, 9.4, 40.1) versus 21.2 months (95% CI, 2.7, 35.0) months (HR, 1.41 [95% CI, 0.49, 4.05]). In Asian patients, fewer grade 3/4 adverse events (AEs), serious AEs (SAEs), grade 3/4 SAEs, and AEs resulting in dose reduction/discontinuation occurred with talazoparib than chemotherapy; for talazoparib, the frequency of these events was lower in Asian patients versus overall EMBRACA population.
Conclusion
In this subgroup analysis, talazoparib numerically improved efficacy versus chemotherapy and was generally well tolerated in Asian patients, with fewer grade 3/4 TEAEs, SAEs, and TEAEs leading to dose modification vs. the overall EMBRACA population.

Citations

Citations to this article as recorded by  
  • HR-positive/HER2-negative breast cancer arising in patients with or without BRCA2 mutation: different biological phenotype and similar prognosis
    Pu-Chun Li, Yi-Fan Zhu, Jia-Ni Pan, Qiao-Yan Zhu, Yu-Yang Liao, Xiao-Wen Ding, Lin-Feng Zheng, Wen-Ming Cao
    Therapeutic Advances in Medical Oncology.2024;[Epub]     CrossRef
  • Detection and analysis of the safety profile of talazoparib based on FAERS database
    Mufei Tang, Peiyan Liu, Linzhe Du, Yuanyuan Li, Jinjin Chen, Yang Li
    Expert Opinion on Drug Safety.2024; : 1.     CrossRef
  • Facing inevitable PARPis resistance: Mechanisms and therapeutic strategies for breast cancer treatment
    Haixia Liu, Xiaohui Chen, Yimin Jia, Hengyi Chen, Xiaohui Wang, Guoxiang Liu, Yang Luo
    Interdisciplinary Medicine.2023;[Epub]     CrossRef
  • Sustained delivery of PARP inhibitor Talazoparib for the treatment of BRCA-deficient ovarian cancer
    Shicheng Yang, Allen Green, Needa Brown, Alexis Robinson, Merline Senat, Bryanna Testino, Daniela M. Dinulescu, Srinivas Sridhar
    Frontiers in Oncology.2023;[Epub]     CrossRef
  • Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, staging and treatment of patients with metastatic breast cancer
    S.-A. Im, A. Gennari, Y.H. Park, J.H. Kim, Z.-F. Jiang, S. Gupta, T.H. Fadjari, K. Tamura, M.Y. Mastura, M.L.T. Abesamis-Tiambeng, E.H. Lim, C.-H. Lin, A. Sookprasert, N. Parinyanitikul, L.-M. Tseng, S.-C. Lee, P. Caguioa, M. Singh, Y. Naito, R.A. Hukom,
    ESMO Open.2023; 8(3): 101541.     CrossRef
  • Molecular Biology Mechanisms and Emerging Therapeutics of Triple-Negative Breast Cancer
    Zhiying Zhang, Rui Zhang, Donghai Li
    Biologics: Targets and Therapy.2023; Volume 17: 113.     CrossRef
  • Development of the PARP inhibitor talazoparib for the treatment of advanced BRCA1 and BRCA2 mutated breast cancer
    Evthokia A. Hobbs, Jennifer K. Litton, Timothy A. Yap
    Expert Opinion on Pharmacotherapy.2021; : 1.     CrossRef
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  • 6 Web of Science
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Gynecologic Cancer
Enhanced Efficacy of Combined Therapy with Checkpoint Kinase 1 Inhibitor and Rucaparib via Regulation of Rad51 Expression in BRCA Wild-Type Epithelial Ovarian Cancer Cells
Hye-yon Cho, Yong-Beom Kim, Wook-ha Park, Jae Hong No
Cancer Res Treat. 2021;53(3):819-828.   Published online December 16, 2020
DOI: https://doi.org/10.4143/crt.2020.1013
AbstractAbstract PDFPubReaderePub
Purpose
This study aimed to evaluate anticancer effects of combination treatment with poly(ADP-ribose) polymerase (PARP) and checkpoint kinase 1 (Chk1) inhibitors in BRCA wild-type ovarian cancer. PARP inhibitors can function as DNA-damaging agents in BRCA wild-type cancer, even if clinical activity is limited. Most epithelial ovarian cancers are characterized by a TP53 mutation causing dysfunction at the G1/S checkpoint, which makes tumor cells highly dependent on Chk1-mediated G/M phase cell-cycle arrest for DNA repair.
Materials and Methods
We investigated the anticancer effects of combination treatment with prexasertib (LY2606368), a selective ATP competitive small molecule inhibitor of Chk1 and Chk2, and rucaparib, a PARP inhibitor, in BRCA wild-type ovarian cancer cell lines (OVCAR3 and SKOV3).
Results
We found that combined treatment significantly decreased cell viability in all cell lines and induced greater DNA damage and apoptosis than in the control and/or using monotherapies. Moreover, we found that prexasertib significantly inhibited homologous recombination–mediated DNA repair and thus showed a marked anticancer effect in combination treatment with rucaparib. The anticancer mechanism of prexasertib and rucaparib was considered to be caused by an impaired G2/M checkpoint due to prexasertib treatment, which forced mitotic catastrophe in the presence of rucaparib.
Conclusion
Our results suggest a novel effective therapeutic strategy for BRCA wild-type epithelial ovarian cancer using a combination of Chk1 and PARP inhibitors.

Citations

Citations to this article as recorded by  
  • ATR, CHK1 and WEE1 inhibitors cause homologous recombination repair deficiency to induce synthetic lethality with PARP inhibitors
    Hannah L. Smith, Elaine Willmore, Lisa Prendergast, Nicola J. Curtin
    British Journal of Cancer.2024; 131(5): 905.     CrossRef
  • Combined strategies with PARP inhibitors for the treatment of BRCA wide type cancer
    Yijun Xie, Di Xiao, Duo Li, Mei Peng, Wei Peng, Huaxin Duan, Xiaoping Yang
    Frontiers in Oncology.2024;[Epub]     CrossRef
  • Update on Combination Strategies of PARP Inhibitors
    Zhuoqun Lin, Lingfang Wang, Ziyu Xing, Fenfen Wang, Xiaodong Cheng
    Cancer Control.2024;[Epub]     CrossRef
  • Molecular Methods for Increasing the Effectiveness of Ovarian Cancer Treatment: A Systematic Review
    Zuzanna Chilimoniuk, Agata Rocka, Martyna Stefaniak, Żaklina Tomczyk, Faustyna Jasielska, Dominika Madras, Agata Filip
    Future Oncology.2022; 18(13): 1627.     CrossRef
  • A Phase 2 study of prexasertib (LY2606368) in platinum resistant or refractory recurrent ovarian cancer
    Panagiotis A. Konstantinopoulos, Jung-min Lee, Bo Gao, Rowan Miller, Jung-Yun Lee, Nicoletta Colombo, Ignace Vergote, Kelly M. Credille, Suzanne R. Young, Samuel McNeely, Xuejing Aimee Wang, Aimee Bence Lin, Ronnie Shapira-Frommer
    Gynecologic Oncology.2022; 167(2): 213.     CrossRef
  • Pharmacological Poly (ADP-Ribose) Polymerase Inhibitors Decrease Mycobacterium tuberculosis Survival in Human Macrophages
    Cassandra L. R. van Doorn, Sanne A. M. Steenbergen, Kimberley V. Walburg, Tom H. M. Ottenhoff
    Frontiers in Immunology.2021;[Epub]     CrossRef
  • 7,417 View
  • 241 Download
  • 8 Web of Science
  • 6 Crossref
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