Zie ook in gerelateerde artikelen.

Raadpleeg ook literatuurlijst niet-toxische middelen en behandelingen specifiek bij eierstokkanker van arts-bioloog drs. Engelbert Valstar

31 juli 2023: In Jama zijn nieuwe studiegegevens van een van onderstaand besproken studies gepubliceerd (studieprotocol  NCT03709316). En deze nieuwe gegevens bevestigen wat dus al eerder werd gepubliceerd.

Ongeacht de kiemlijn BRCA-mutatiestatus bereikten patiënten met eerste diagnose van uitgezaaide eierstokkanker met niraparib - Zejul een veel betere ziekteprogressievrije tijd in vergelijking met een placebo , 8,3 maanden versus 24,8 maanden met een verminderd risico op overlijden van 55 procent. 

Belangrijkste conclusie:

In the PRIME phase 3 randomized clinical trial of 384 patients with newly diagnosed advanced ovarian cancer after receiving first-line platinum-based chemotherapy, including those who underwent R0 resection at primary debulking surgery, treatment with niraparib with an individualized starting dose significantly extended progression-free survival vs placebo and reduced the risk of disease progression or death by 55%.

Zie verder hieronder meer details over deze studie of klik op de titel van laatst gepubliceerde studierapport, abstract staat verderop in artikel:

Treatment With Niraparib Maintenance Therapy in Patients With Newly Diagnosed Advanced Ovarian CancerA Phase 3 Randomized Clinical Trial

7 december 2021: Bron: virtueel COSA 2021

Uit een samengestelde analyse van verschillende fase III studies is definitief aangetoond dat een onderhoudsbehandeling met de parpremmer niraparib - Zejul leidt tot een veel langere progressievrije overleving bij patiënten met BRCA-gemuteerde eierstokkanker. Maar ook bij patiënten met niet BRCA-gemuteerde eierstokkanker was er een behoorlijk langere overleving te zien. En ook belangrijk zonder extra bijwerkingen.
Of nu het zorginstituut nu hun advies tot niraparib - Zejul opnemen in de basisverzekering en gaat vergoeden moet blijken. De resultaten zijn in ieder geval heel robuust en statistisch significant. 

Deze uitkomst van een samenvatting van de werkzaamheid en veiligheid in de fase 3, gerandomiseerde, dubbelblinde, placebo gecontroleerde, multicenter studies PRIMA studie, NOVA studie en NORA studies werden gepresenteerd tijdens de virtuele 48e jaarlijkse wetenschappelijke bijeenkomst van de Clinical Oncology Society of Australia (COSA ), van 16 – 18 november 2021.

Patiënten opgenomen in de PRIMA studie hadden nieuw gediagnosticeerde gevorderde eierstokkanker. Alle vertoonden stadium 3/4, hooggradige, sereuze of endometrioïde tumoren en hadden eerder een volledige of gedeeltelijke respons gezien op eerstelijns platina-gebaseerde chemotherapie. Subgroepanalyse op basis van tumor BRCA-mutatiestatus was vooraf gespecificeerd.

Patiënten in de NOVA studie en de NORA studie hadden platinagevoelige, hooggradige, sereuze eierstokkanker. Ze hadden ten minste twee kuren met op platina gebaseerde chemotherapie gekregen. Subgroepanalyse naar kiemlijn BRCA-mutatiestatus was vooraf gespecificeerd in beide onderzoeken. Het primaire eindpunt in alle drie de onderzoeken was progressievrije overleving zoals bepaald door middel van een geblindeerde onafhankelijke centrale beoordeling.

Verdeeld over de drie genoemde studies was dit de verdeling in wel of niet BRCA gemuteerd:
  • PRIMA: N=223 (n=148 BRCA1-mutated, n=75 BRCA2-mutated)

  • NOVA: N=203 (n=128 BRCA1-mutated, n=69 BRCA2-mutated, n=13 BRCA1- and BRCA2-mutated)

  • NORA: N=100 (n=78 BRCA1-mutated, n=21 BRCA2-mutated, n=1 BRCA1- and BRCA2-mutated)


De meest voorkomende tijdens de behandeling optredende bijwerkingen waren trombocytopenie, anemie - bloedarmoede, neutropenie en hypertensie - verhoogde bloeddruk in alle drie de onderzoeken.

Resultaten uit de NOVA studie: zie dit studieverslag op de website van de producent.

Met aangetoonde BRCA mutatie versus placebo :

Graph showing PFS in gBRCAm cohort with 74% reduction in risk of disease progression or death.


Met BRCA wild type dus geen aangetoonde BRCA mutatie versus placebo:

Graph showing PFS in the BRCA wild-type, HRDpos subpopulation.

Resultaten uit de PRIMA studie waarin eierstokkankerpatiënten met vergevorderde ziekte waren opgenomen ongeacht hun mutatiestatus zijn ook op de website van de producent te vinden:

Graph showing PFS in overall population with 38% reduction in risk of disease progression or death.

Voor de Nora studie zie deze publicatie met daaronder gerelateerde artikelen:

Abstract

Background: This study evaluated maintenance treatment with niraparib, a potent inhibitor of poly(ADP-ribose) polymerase 1/2, in patients with platinum-sensitive recurrent ovarian cancer.

Patients and methods: In this phase III, double-blind, placebo-controlled study conducted at 30 centers in China, adults with platinum-sensitive recurrent ovarian cancer who had responded to their most recent platinum-containing chemotherapy were randomized 2 : 1 to receive oral niraparib (300 mg/day) or matched placebo until disease progression or unacceptable toxicity (NCT03705156). Following a protocol amendment, patients with a bodyweight <77 kg or a platelet count <150 × 103/μl received 200 mg/day, and all other patients 300 mg/day, as an individualized starting dose (ISD). Randomization was carried out by an interactive web response system and stratified by BRCA mutation, time to recurrence following penultimate chemotherapy, and response to most recent chemotherapy. The primary endpoint was progression-free survival (PFS) assessed by blinded independent central review.

Results: Between 26 September 2017 and 2 February 2019, 265 patients were randomized to receive niraparib (n = 177) or placebo (n = 88); 249 patients received an ISD (300 mg, n = 14; 200 mg, n = 235) as per protocol. In the intention-to-treat population, median PFS was significantly longer for patients receiving niraparib versus placebo: 18.3 [95% confidence interval (CI), 10.9-not evaluable] versus 5.4 (95% CI, 3.7-5.7) months [hazard ratio (HR) = 0.32; 95% CI, 0.23-0.45; P < 0.0001], and a similar PFS benefit was observed in patients receiving an ISD, regardless of BRCA mutation status. Grade ≥3 treatment-emergent adverse events occurred in 50.8% and 19.3% of patients who received niraparib and placebo, respectively; the most common events were neutrophil count decreased (20.3% versus 8.0%) and anemia (14.7% versus 2.3%).

Conclusions: Niraparib maintenance treatment reduced the risk of disease progression or death by 68% and prolonged PFS compared to placebo in patients with platinum-sensitive recurrent ovarian cancer. Individualized niraparib dosing is effective and safe and should be considered standard practice in this setting.

Keywords: maintenance therapy; niraparib; ovarian cancer.

Conflict of interest statement

Disclosure MRM has received fees for serving on advisory boards from Tesaro, GSK, Clovis Oncology, AstraZeneca, and Zai Lab and speaker fees from AstraZeneca, Tesaro, GSK, Zai Lab, and Roche. The other authors have declared no conflicts of interest. Data sharing From the publication date, upon reasonable request to the corresponding author (researchers who provide a methodologically sound proposal and assuming use of the data to meet the goals of this proposal), individual participant data that underlie the results reported in this article (text, tables, and figures) can be made available after de-identification. The study protocol can also be made available with reasonable request.

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Cited by 6 articles




niraparib maintenance therapy prolonged PFS in patients with newly diagnosed advanced Ovarian Cancer regardless of postoperative residual disease or biomarker status. The ISD was effective and safe in the first-line maintenance setting.

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Abstract
Treatment With Niraparib Maintenance Therapy in Patients With Newly Diagnosed Advanced Ovarian Cancer: A Randomized Clinical Trial
Key Points

Question  Does treatment with niraparib prolong progression-free survival in patients with newly diagnosed advanced ovarian cancer?

Finding  In the PRIME phase 3 randomized clinical trial of 384 patients with newly diagnosed advanced ovarian cancer after receiving first-line platinum-based chemotherapy, including those who underwent R0 resection at primary debulking surgery, treatment with niraparib with an individualized starting dose significantly extended progression-free survival vs placebo and reduced the risk of disease progression or death by 55%.

Meaning  The results of this randomized clinical trial support niraparib monotherapy as a standard of care after first-line platinum-based chemotherapy in a broad patient population with advanced ovarian cancer.

Abstract

Importance  The efficacy of niraparib maintenance therapy with an individualized starting dose (ISD) warrants further investigation in a broad population with newly diagnosed advanced ovarian cancer (aOC), including patients without postoperative residual disease.

Objective  To evaluate the efficacy and safety of niraparib with an ISD in a broad population with newly diagnosed aOC (R0 resection permitted).

Design, Setting, and Participants  This multicenter, randomized, double-blind, placebo-controlled, phase 3 study was conducted in China and enrolled 384 patients with newly diagnosed aOC who received primary or interval debulking surgery and responded to treatment with first-line platinum-based chemotherapy. By data cutoff (September 30, 2021), median follow-up for progression-free survival (PFS) was 27.5 (IQR, 24.7-30.4) months.

Interventions  Patients were randomized 2:1 to receive niraparib or placebo with ISD (200 mg/d for those with a body weight of <77 kg and/or platelet count of <150 ×103/μL [to convert to ×109/μL, multiply by 1] at baseline; 300 mg/d otherwise) stratified by germline BRCA variant status, tumor homologous recombination deficiency status, neoadjuvant chemotherapy, and response to first-line platinum-based chemotherapy.

Main Outcomes and Measurements  The primary end point was blinded, independent central review–assessed PFS in the intention-to-treat population.

Results  A total of 384 patients were randomized (255 niraparib [66.4%]; median age, 53 [32-77] years; 129 placebo [33.6%]; median age, 54 [33-77] years), and 375 (247 niraparib [65.9%], 128 placebo [34.1%]) received treatment at a dose of 200 mg per day. Median PFS with niraparib vs placebo was 24.8 vs 8.3 months (hazard ratio , 0.45; 95% CI, 0.34-0.60; P < .001) in the intention-to-treat population; not reached vs 10.8 months (HR, 0.40; 95% CI, 0.23-0.68) and 19.3 vs 8.3 months (HR, 0.48; 95% CI, 0.34-0.67) in patients with and without germline BRCA variants, respectively; not reached vs 11.0 months (HR, 0.48; 95% CI, 0.34-0.68) and 16.6 vs 5.5 months (HR, 0.41; 95% CI, 0.22-0.75) in homologous recombination deficient and proficient patients, respectively; and 24.8 vs 8.3 months (HR, 0.44; 95% CI, 0.32-0.61) and 16.5 vs 8.3 months (HR, 0.27; 95% CI, 0.10-0.72) in those with optimal and suboptimal debulking, respectively. Similar proportions of niraparib-treated and placebo-treated patients (6.7% vs 5.4%) discontinued treatment due to treatment-emergent adverse events.

Conclusion and Relevance  This randomized clinical trial found that niraparib maintenance therapy prolonged PFS in patients with newly diagnosed aOC regardless of postoperative residual disease or biomarker status. The ISD was effective and safe in the first-line maintenance setting.

Trial RegistrationClinicalTrials.gov Identifier: NCT03709316  

Article Information

Accepted for Publication: May 4, 2023.

Published Online: July 13, 2023. doi:10.1001/jamaoncol.2023.2283

Open Access: This is an open access article distributed under the terms of the CC-BY-NC-ND License. © 2023 Li N et al. JAMA Oncology.

Corresponding Author: Lingying Wu, MD, PhD, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 Panjiayuan Nali, Chaoyang District, Beijing 100021, China (wulingying@csco.org.cn).

Author Contributions: Dr L. Wu had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Drs N. Li, Zhu, and Yin are co–first authors and contributed equally to the manuscript.

Concept and design: N. Li, Jing Wang, X. Wu, Zhen, Hang, Hou, L. Wu.

Acquisition, analysis, or interpretation of data: All authors.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: N. Li, Zhen, Hang, Hou.

Obtained funding: L. Wu.

Administrative, technical, or material support: N. Li, Zhu, Yin, Jing Wang, L. Pan, Kong, Zheng, J. Liu, X. Wu, L. Wang, Huang, K. Wang, Zou, Zhao, C. Wang, Lu, Lin, Lou, G. Li, Qu, H. Yang, Zhang, Cai, Y. Pan, Hao, Z. Liu, Cui, Y. Yang, Yao, Zhen, Hang, Juan Wang, L. Wu.

Supervision: Hou, L. Wu.

Conflict of Interest Disclosures: Drs Zhen, Hang, Hou, and Juan Wang reported being employees of and holding shares and stock options in Zai Lab during the conduct of the study. Dr L. Wu reported grants from Zai Lab during the conduct of the study. No other disclosures were reported.

Funding/Support: This study was funded by Zai Lab (Shanghai) Co, Ltd, and partially supported by the National Major Scientific and Technological Special Project for Significant New Drugs Development in 2020 (China; grant 2020ZX09101-014).

Role of the Funder/Sponsor: The study sponsor, Zai Lab, supported the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Meeting Presentations: Results from this study were presented in part as oral presentations at the 2022 Society of Gynecologic Oncology (SGO) Annual Meeting (Phoenix, Arizona; March 18-21, 2022), European Society for Medical Oncology (ESMO) Gynaecological Cancers Congress 2022 (Valencia, Spain; June 17-18, 2022), and ESMO Gynaecological Cancers Congress 2023 (Valencia, Spain; January 23-24, 2023), and as posters at the 2022 American Society of Clinical Oncology Annual Meeting (ASCO; Chicago, Illinois; June 3-7, 2022), the 2022 International Gynecologic Cancer Society Annual Global Meeting (New York, New York; September 29-October 1, 2022), 2023 SGO Annual Meeting (Tampa, Florida; March 25-28, 2023), and the 2023 ASCO Annual Meeting (Chicago, Illinois; June 2-6, 2023).

Data Sharing Statement: See Supplement 4.

Additional Contributions: We thank the patients, the investigators, and their teams who took part in this study. Zai Lab provided funding for third-party writing assistance for this article from Jinlong Guo, PhD, Costello Medical. He did not receive any additional compensation beyond his usual salary.

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