Olaparib Maintenance Monotherapy in Asian Patients with Platinum-Sensitive Relapsed Ovarian Cancer: Phase III Trial (L-MOCA)

Gao, Qinglei; Zhu, Jianqing; Zhao, Weidong; Huang, Yi; An, Ruifang; Zheng, Hong; Qu, Pengpeng; Wang, Li; Zhou, Qi; Wang, Danbo; Lou, Ge; Wang, Jing; Wang, Ke; Low, J.S.H.; Kong, Beihua; Rozita, Abdul Malik; Sen, Lim Chun; Yin, Rutie; Xie, Xing; Liu, Jihong; Sun, Wei; Su, Jingya; Zhang, Chunyi; Zang, Rongyu; Ma, Ding

doi:10.1158/1078-0432.ccr-21-3023

Cited by 20 publications

(22 citation statements)

References 28 publications

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“…An updated median OS of 32.7 months at a median follow-up of 33.1 months for the phase IIIb OPINION study was published at the 2022 ESMO Annual Meeting; the Kaplan-Meier analysis showed OS rates of 65.8% and 54.9% at 24 and 30 months, respectively, and these data further support the use of olaparib maintenance therapy for the treatment of non-gBRCAm PSROC (Poveda Velasco et al, 2022). The L-MOCA study was the first clinical study to assess the efficacy and tolerability of olaparib maintenance treatment in Asian PSROC patients, and an mPFS Frontiers in Pharmacology frontiersin.org of 16.1 months for all patients as of 25 December 2020, was reported (Gao et al, 2022). Subgroup analysis showed that compared to the corresponding wild-type group mPFS, the BRCA mutation group mPFS (21.2 months vs 11.0 months) and the HRR mutation group mPFS (18.3 months vs 13.3 months) were better.…”

Section: Second-line and Beyond Treatment With Olaparibsupporting

confidence: 56%

“…The AE incidence was 99.1%, with the most common AE being anemia (76.4%), and 9.4% of patients discontinued treatment due to treatment-related AEs. This study showed that in Asian PSROC patients, olaparib maintenance therapy had significant efficacy regardless of BRCA status and was well tolerated by patients (Gao et al, 2022). In 2014, the Food and Drug Administration (FDA) approved olaparib in this population based on the results of Study 42 (NCT01078662), in which patients with recurrent gBRCAm OC who had received at least three chemotherapy regimens responded durably to olaparib (Figure 1) (Domchek et al, 2016).…”

Section: Second-line and Beyond Treatment With Olaparibmentioning

confidence: 89%

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Targeted therapy and immunotherapy: Diamonds in the rough in the treatment of epithelial ovarian cancer

Huang

Shan

et al. 2023

Front. Pharmacol.

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Currently, for ovarian cancer, which has the highest mortality rate among all gynecological cancers, the standard treatment protocol is initial tumor cytoreductive surgery followed by platinum-based combination chemotherapy. Although the survival rate after standard treatment has improved, the therapeutic effect of traditional chemotherapy is very limited due to problems such as resistance to platinum-based drugs and recurrence. With the advent of the precision medicine era, molecular targeted therapy has gradually entered clinicians’ view, and individualized precision therapy has been realized, surpassing the limitations of traditional therapy. The detection of genetic mutations affecting treatment, especially breast cancer susceptibility gene (BRCA) mutations and mutations of other homologous recombination repair defect (HRD) genes, can guide the targeted drug treatment of patients, effectively improve the treatment effect and achieve a better patient prognosis. This article reviews different sites and pathways of targeted therapy, including angiogenesis, cell cycle and DNA repair, and immune and metabolic pathways, and the latest research progress from preclinical and clinical trials related to ovarian cancer therapy.

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Section: Second-line and Beyond Treatment With Olaparibsupporting

confidence: 56%

Section: Second-line and Beyond Treatment With Olaparibmentioning

confidence: 89%

Targeted therapy and immunotherapy: Diamonds in the rough in the treatment of epithelial ovarian cancer

Huang

Shan

et al. 2023

Front. Pharmacol.

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“…In the phase IIIb OPINION trial (NCT03402841) (Poveda et al, 2022), maintenance olaparib demonstrated clinical benefit in patients without a germline BRCA1/BRCA2 mutation (gBRCAm). Additionally, the phase Ⅲ trial L-MOCA (NCT03534453) (Gao et al, 2022) ) has demonstrated that PARP inhibition is also an effective treatment for patients with metastatic breast cancer with gPALB2 (ORR, 82%) and sBRCA1/2 (ORR, 50%) mutations, significantly expanding the population of breast cancer patients who may benefit from PARPi, indicating that not only gBRCA1/ 2 mutation carriers, but also other mutations in homologous recombination-related genes may benefit from PARPi (Tung et al, 2020). Likewise, according to an article published in the Lancet Oncology July 2022 (NCT03404960), PARPi combined with nivolumab or niraparib has shown effectiveness among pancreatic cancer patients, even though the BRCA mutation rate in pancreatic cancer is only about 4%-7% (Reiss et al, 2022).…”

Section: Current Approved Parp Inhibitorsmentioning

confidence: 99%

Section: Current Approved Parp Inhibitorsmentioning

confidence: 99%

Current status and future promise of next-generation poly (ADP-Ribose) polymerase 1-selective inhibitor AZD5305

Zheng

Min

2023

Front. Pharmacol.

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The family of poly (ADP-ribose) polymerases (PARPs) consists of 17 members, which have been demonstrated as having effects on a series of cellular processes, including DNA replication and repair. PARP inhibitors (PARPi) suppress DNA repair through “PARP trapping”, thus, constitute an important treatment option for cancer nowadays. In addition, PARP inhibition and homologous recombination repair (HRR) defects are synthetically lethal, giving a promising therapeutic for homologous recombination repair deficient (HRD) tumors including BRCA mutation. However, overlapping hematologic toxicity causes PARPi to fail in combination with some first-line chemotherapies. Furthermore, recent literature has demonstrated that PARP1 inhibition and PARP1-DNA trapping are key for antitumor activity in HRD cancer models. Currently approved PARPi have shown varying levels of selectivity for the entire 17-member PARP family, hence contribute to toxicity. Together, these findings above have provided the necessity and feasibility of developing next-generation PARPi with improved selectivity for PARP1, expanding significant clinical values and wide application prospects both in monotherapy and combination with other anticancer agents. In this review, we summery the latest research of current approved PARPi, discuss the current status and future promise of next-generation PARP1-selective inhibitor AZD5305, including its reported progress up to now and anticipated impact on clinical.

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“…We present the case of a 56-year-old woman with histologically proven primary ovarian cancer who suffered from three recurrences and four line therapies (Figure 1). She participated in the AICE trial 9 and L-MOCA trial 10 , and provided a written informed consent. These two study protocols were both approved by the ethics committee of Zhongshan Hospital, Fudan University (Approval number: B2014-117, B2018-068R).…”

Section: Case Reportmentioning

confidence: 99%

Angiogenic Burst After Parp Inhibitor Maintenance Therapy in Relapsed Ovarian Cancer: A Case Report

Liu¹,

Luo²,

Gao³

et al. 2022

Preprint

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In the post-PARP inhibitor era, potential changes in tumor biology after maintenance therapy have not been well investigated in recurrent ovarian cancer. We reported a case with alterations in the clinical and histological features of multiple relapsed disease associated with PARP inhibitor maintenance therapy. The patient with high-grade serous carcinoma exhibited BRCA wildtype and homologous recombination proficiency status, and suffered from three recurrences and surgeries accordingly. Olaparib maintenance had been used during the second-line therapy. We compared the differences in clinics and pathology among three recurrences and relapsed lesions. Disease-free survivals were dramatically decreased after the exposure to olaparib. At exploration of quaternary cytoreduction, the relapsed tumor was characterized by a carcinomatosis-like metastasis pattern and an easy tendency of bleeding. Tumor cytopathological changes and alterations were observed in both the tumoral and non-tumoral stroma, among relapsed tumor tissues derived from secondary, tertiary and quaternary cytoreduction. Histopathology indicated hemorrhage, necrosis, atypical tumor cells, massive angiogenesis, and decreased CD8+ tumor-infiltrating lymphocytes, particularly in the third relapsed disease. To our knowledge, this is the first report to show a unique metastatic pattern of angiogenic burst after PARP inhibitor maintenance therapy in ovarian cancer, which seemed to trigger invasive tumor growth and immune suppression. Further prospective studies and translational research focusing cytoreductive surgery after PARP inhibitor could progressively lead to an understanding of the biological behavior and metastatic patterns.

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Olaparib Maintenance Monotherapy in Asian Patients with Platinum-Sensitive Relapsed Ovarian Cancer: Phase III Trial (L-MOCA)

Cited by 20 publications

References 28 publications

Targeted therapy and immunotherapy: Diamonds in the rough in the treatment of epithelial ovarian cancer

Targeted therapy and immunotherapy: Diamonds in the rough in the treatment of epithelial ovarian cancer

Current status and future promise of next-generation poly (ADP-Ribose) polymerase 1-selective inhibitor AZD5305

Angiogenic Burst After Parp Inhibitor Maintenance Therapy in Relapsed Ovarian Cancer: A Case Report

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