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      Real-world Study on the Effect of PARPi as Maintenance Therapy on Platinum Sensitivity after First- and Second-line Chemotherapy in Patients with Recurrent High-grade Serous Epithelial Ovarian Cancer

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          Abstract

          Background: This study investigated the effect of poly(ADP-ribose) polymerase inhibitors (PARPi) as maintenance therapy after first- and second-line chemotherapy on platinum sensitivity in patients with recurrent high-grade serous epithelial ovarian cancer (rHGSOC).

          Methods: This study retrospectively analyzed 172 patients with rHGSOC treated at Zhejiang Cancer Hospital and Jiaxing Maternity and Child Health Care Hospital between January 2017 and December 2021. The 1st-PARPi group comprised patients who received a PARPi as maintenance therapy after first-line chemotherapy ( n=23), and the 1st-control group comprised those who did not ( n = 105). Similarly, the 2nd-PARPi group comprised patients not given a PARPi in their first-line treatment ( n = 30), and the 2nd-control group comprised those who were given a PARPi ( n = 89).

          Results: Among the 23 patients in the 1st-PARPi group and the 105 patients in the 1st-control group, nine and 99 were platinum-sensitive, and 14 and six were platinum-resistant, respectively (hazard ratio [HR]: 14.46, P < 0.0001). Among the 30 patients in the 2nd-PARPi group and 89 patients in the 2nd-control group, 10 and 71 were platinum-sensitive, and 20 and 18 were platinum-resistant, respectively (HR: 4.37, P < 0.0001). Age, stage, residual tumor, the courses of platinum-based chemotherapy, and breast cancer susceptibility gene mutations were not associated with platinum sensitivity when using a PARPi as maintenance therapy after first- and second-line chemotherapy.

          Conclusion: Patients with rHGSOC using a PARPi were more likely to be platinum-sensitive and develop platinum resistance independent of PARPi duration. Care should be taken when using a PARPi as maintenance therapy after first- and second-line chemotherapy.

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          Most cited references76

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          Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

          This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.
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            Cancer statistics, 2022

            Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence and outcomes. Incidence data (through 2018) were collected by the Surveillance, Epidemiology, and End Results program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data (through 2019) were collected by the National Center for Health Statistics. In 2022, 1,918,030 new cancer cases and 609,360 cancer deaths are projected to occur in the United States, including approximately 350 deaths per day from lung cancer, the leading cause of cancer death. Incidence during 2014 through 2018 continued a slow increase for female breast cancer (by 0.5% annually) and remained stable for prostate cancer, despite a 4% to 6% annual increase for advanced disease since 2011. Consequently, the proportion of prostate cancer diagnosed at a distant stage increased from 3.9% to 8.2% over the past decade. In contrast, lung cancer incidence continued to decline steeply for advanced disease while rates for localized-stage increased suddenly by 4.5% annually, contributing to gains both in the proportion of localized-stage diagnoses (from 17% in 2004 to 28% in 2018) and 3-year relative survival (from 21% to 31%). Mortality patterns reflect incidence trends, with declines accelerating for lung cancer, slowing for breast cancer, and stabilizing for prostate cancer. In summary, progress has stagnated for breast and prostate cancers but strengthened for lung cancer, coinciding with changes in medical practice related to cancer screening and/or treatment. More targeted cancer control interventions and investment in improved early detection and treatment would facilitate reductions in cancer mortality.
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              Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer

              Most women with newly diagnosed advanced ovarian cancer have a relapse within 3 years after standard treatment with surgery and platinum-based chemotherapy. The benefit of the oral poly(adenosine diphosphate-ribose) polymerase inhibitor olaparib in relapsed disease has been well established, but the benefit of olaparib as maintenance therapy in newly diagnosed disease is uncertain.
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                Author and article information

                Journal
                CCDT
                Curr Cancer Drug Targets
                Current Cancer Drug Targets
                Curr. Cancer Drug Targets
                Bentham Science Publishers
                1568-0096
                1873-5576
                01 January 2024
                : 24
                : 7
                : 733-748
                Affiliations
                [1 ] deptDepartment of Gynecologic Oncology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM) , Chinese Academy of Sciences , Hangzhou, , Zhejiang, , 310022, , China;
                [2 ] deptDepartment of Gynecologic Oncology, Jiaxing Maternity and Child Health Care Hospital, Jiaxing , Zhejiang, , 314000, , China
                Author notes
                [* ]Address correspondence to this author at the Department of Gynecologic Oncology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, China; E-mail: zhangyl@ 123456zjcc.org.cn
                Article
                CCDT-24-7-733
                10.2174/0115680096271476231226174810
                bfb3a703-e2eb-4648-8df7-58aee3a07789
                Copyright @ 2024

                © 2024 The Author(s). Published by Bentham Science Publisher. This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode

                History
                : 29 August 2023
                : 06 December 2023
                : 12 December 2023
                Categories
                Medicine, Oncology, Pharmacology

                Medicine,Chemistry,Life sciences
                residual tumor,PARP inhibitor,platinum resistance,platinum-sensitive,BRCA status,High-grade serous epithelial ovarian cancer

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