Zie ook in gerelateerde artikelen hieronder of hiernaast

20 oktober 2024: Bron: 

Uit de eindresultaten van de gerandomiseerde placebo gecontroleerde Fase III PRIMA/ENGOT-OV26/GOG-3012 studie blijkt dat niraparib - Zejul als eerstelijns behandeling bij patiënten met bij diagnose gevorderde eierstokkanker stadium III en IV na chemobehandeling en een hoog risico op een recidief voor een verdubbeling te zorgen van de overall overleving op 5-jaars meting in vergelijking met een placebo. 

In onderstaande grafiek zijn de resultaten en karakteristieken van de deelnemende patiënten te lezen:

Table 1. Subsequent anticancer therapies by treatment arm in the overall and HRd populations

Empty Cell NiraparibPlacebo
Any subsequent anticancer therapyHRd (n = 247)Overall (n = 487)HRd (n = 126)Overall (n = 246)
Total, n (%) 141 (57.1) 325 (66.7) 94 (74.6) 180 (73.2)
Number of lines of subsequent therapy during follow-up, n (%)
 1 44 (17.8) 94 (19.3) 39 (31.0) 60 (24.4)
 2 37 (15.0) 90 (18.5) 18 (14.3) 46 (18.7)
 3 24 (9.7) 58 (11.9) 20 (15.9) 34 (13.8)
 ≥4 36 (14.6) 83 (17.0) 16 (12.7) 37 (15.0)
Surgery, n (%) 41 (16.6) 77 (15.8) 19 (15.1) 37 (15.0)
Radiotherapy, n (%) 20 (8.1) 41 (8.4) 11 (8.7) 19 (7.7)
Platinum-based chemotherapya, n (%) 126 (51.0) 285 (58.5) 81 (64.3) 153 (62.2)
Bevacizumab or bevacizumab biosimilar, n (%) 77 (31.2) 189 (38.8) 35 (27.8) 88 (35.8)
Taxaneb, n (%) 83 (33.6) 203 (41.7) 42 (33.3) 84 (34.1)
Doxorubicinc, n (%) 91 (36.8) 223 (45.8) 60 (47.6) 130 (52.8)
Gemcitabined, n (%) 82 (33.2) 172 (35.3) 40 (31.7) 89 (36.2)
PARP inhibitor, n (%) 39 (15.8) 57 (11.7) 61 (48.4) 93 (37.8)
 Niraparib 12 (4.9) 16 (3.3) 19 (15.1) 35 (14.2)
 Niraparib tosylate monohydrate 1 (0.4) 1 (0.2) 0 (0) 0 (0)
 Olaparib 24 (9.7) 34 (7.0) 38 (30.2) 53 (21.5)
 Rucaparib 3 (1.2) 7 (1.4) 5 (4.0) 8 (3.3)
 Talazoparib 0 (0) 0 (0) 1 (0.8) 1 (0.4)
HRd, homologous recombination deficient; PARP, poly(ADP)-ribose polymerase.
a
Includes carboplatin, cisplatin, and oxaliplatin.
b
Includes docetaxel and paclitaxel.
c
Includes doxorubicin, doxorubicin hydrochloride, liposomal doxorubicin, liposomal doxorubicin hydrochloride, pegylated liposomal doxorubicin, and pegylated liposomal doxorubicin hydrochloride.
d
Includes gemcitabine and gemcitabine hydrochloride.

Het volledige studierapport bevat veel meer grafieken en uitleg. Klik op de titel van het abstract voor het volledige studierapport:

Annals of Oncology

Available online 14 September 2024
In Press, Corrected Proof
Annals of Oncology
Original article

Niraparib first-line maintenance therapy in patients with newly diagnosed advanced ovarian cancer: final overall survival results from the PRIMA/ENGOT-OV26/GOG-3012 trial☆

https://doi.org/10.1016/j.annonc.2024.08.2241Get rights and content
Under a Creative Commons license
open access

Highlights

  • •
    No difference in OS was observed between treatment arms in the overall population or by HRD/BRCA status.
  • •
    In the HRd population, patients alive at 5 years were two times as likely to be progression free with niraparib than placebo.
  • •
    A higher rate of subsequent poly(ADP)-ribose polymerase inhibitor therapy was observed in patients who received a placebo.
  • •
    Long-term safety findings were consistent with the known safety profile of niraparib; no new safety signals were observed.

Background

The phase III PRIMA/ENGOT-OV26/GOG-3012 trial met its primary endpoint. Niraparib first-line maintenance significantly prolonged progression-free survival (PFS) among patients with newly diagnosed advanced ovarian cancer that responded to first-line platinum-based chemotherapy, regardless of homologous recombination deficiency (HRD) status. Final overall survival (OS) results are reported.

Patients and methods

Patients were randomized 2:1 to niraparib or placebo, stratified by response to first-line treatment, receipt of neoadjuvant chemotherapy, and tumor HRD status. After reaching 60% target maturity, OS was evaluated via a stratified log-rank test using randomization stratification factors and summarized using Kaplan–Meier methodology. OS testing was hierarchical [overall population first, then the homologous recombination-deficient (HRd) population]. Other secondary outcomes and long-term safety were assessed; an updated, ad hoc analysis of investigator-assessed PFS was also conducted (cut-off date, 8 April 2024).

Results

The median follow-up was 73.9 months. In the overall population, the OS hazard ratio was 1.01 [95% confidence interval (CI) 0.84-1.23; P = 0.8834] for niraparib (n = 487) versus placebo (n = 246). In the HRd (n = 373) and homologous recombination-proficient (n = 249) populations, the OS hazard ratios were 0.95 (95% CI 0.70-1.29) and 0.93 (95% CI 0.69-1.26), respectively. Subsequent poly(ADP-ribose) polymerase inhibitor therapy was received by 11.7% and 15.8% of niraparib patients and 37.8% and 48.4% of placebo patients in the overall and HRd populations, respectively. The 5-year PFS rate numerically favored niraparib in the overall (niraparib, 22%; placebo, 12%) and HRd populations (niraparib, 35%; placebo, 16%). Myelodysplastic syndromes/acute myeloid leukemia incidence was <2.5% (niraparib, 2.3%; placebo, 1.6%). No new safety signals were observed.

Conclusions

In patients with newly diagnosed advanced ovarian cancer at high risk of recurrence, there was no difference in OS between treatment arms. In the HRd population, patients alive at 5 years were two times as likely to be progression free with niraparib treatment than placebo. Long-term safety remained consistent with the established niraparib safety profile.

Acknowledgements

We thank the patients, their families, the clinical investigators, and site personnel who participated in the study, and the members of the trial-specific independent data and safety monitoring committee. Writing and editorial support, funded by GSK (Waltham, MA) and coordinated by Hasan H. Jamal, MSc of GSK, was provided by Betsy C. Taylor, PhD, CMPP, Jessica M. Weems, PhD, and Mary C. Wiggin of Ashfield MedComms, an Inizio company. GSK sponsored the study, provided the study drugs, and collaborated with the study investigators on the study design and the collection, analysis, and interpretation of the data.

Authors’ contributions

All authors contributed to drafting the manuscript with editorial and writing assistance funded by the sponsor, had access to all the data in the study, provided final approval to publish, and agreed to be accountable for all aspects of the manuscript.

Funding

This work was supported by GSK (no grant number is applicable).

Disclosure

BMJ reports consulting fees from Acrivon Therapeutics, Adaptimmune, Agenus, Akesobio, Amgen, Aravive, AstraZeneca, Bayer, Clovis Oncology, Eisai, Elevar Therapeutics, EMD Serono, Genmab/Seagen, GOG Foundation, Gradalis, Hengrui, ImmunoGen, Iovance Biotherapeutics, Karyopharm Therapeutics, Laekna, MacroGenics, MSD, Mersana Therapeutics, Myriad Genetics, Novartis, Novocure, OncoC4, Panavance Therapeutics, Pieris, Pfizer, Puma Biotechnology, Regeneron, Roche/Genentech, Sorrento, Tesaro/GSK, US Oncology Research, VBL Therapeutics, Verastem Oncology, and Zentalis and speakers’ bureau honoraria from AstraZeneca, Eisai, Myriad Genetics, Roche/Genentech, and Tesaro/GSK. MPBG reports consulting or advisory role fees from AstraZeneca, Clovis Oncology, GSK, MSD, PharmaMar, and Roche and travel support from AstraZeneca, GSK, MSD, PharmaMar, and Roche. BP reports consulting fees from AstraZeneca, BioNTech, Imunon, Daiichi-Sankyo, Duality Bio, Eisai, GOG Foundation, ImmunoGen, Imvax, Incyte, InxMed, Lily, Onconova Therapeutics, OnCusp Therapeutics, R Pharm US, Regeneron, Seagen, Signatera, Sutro Biopharma, and Tesaro/GSK; payment or honoraria for lectures presentations, speakers’ bureaus, manuscript writing, or educational events from Albert Einstein-Montefiore, Bio Ascend, Colorado University, Curio, Lankenau Hospital, OncLive, Peer View, PERS, Vaniam Group, and Yale University; grants or contracts from Acrivon Therapeutics, Agenus, Alkermes, AstraZeneca, Celgene, Imunon, Clovis Oncology, Duality Bio, Eisai, I-Mab Biopharma, ImmunoGen, Incyte, InxMed, Karyopharm Therapeutics, LOXO Oncology/Lily, MSD, Mersana Therapeutics, Novocure, NRG Oncology, Onconova Therapeutics, Roche/Genentech, Seagen, Sutro Biopharma, Takeda, Tesaro/GSK, Toray Industries, VBL Therapeutics, and Xencor; support for attending meetings and/or travel from GOG Partners; participation on a data safety monitoring board or advisory board for AstraZeneca, BioNTech, Imunon, GOG Foundation, I-Mab Biopharma, Imvax, InxMed, MSD, Mersana Therapeutics, Nuvation Bio, Sutro Biopharma, Tesaro/GSK, and Toray Industries; and leadership or fiduciary roles in GOG Foundation, GOG Partners, NYOB Society (Vice President), and SGO Board of Directors. IV reports payments for consulting from Akesobio, Bristol Myers Squibb, Deciphera, Eisai, Elevar Therapeutics, Genmab, GSK, ITM, Jazz Pharmaceuticals, Karyopharm Therapeutics, MSD, Novocure, Oncoinvent, Sanofi, Regeneron, Roche, Seagen, Sotio, and Zentalis and for data monitoring committees from Agenus, AstraZeneca, Corcept Therapeutics, Daiichi-Sankyo, Exelixis, ImmunoGen, Kronos Bio, Mersana Therapeutics, Novartis, OncXerna Therapeutics, Roche, and Verastem Oncology. WG reports consulting and speaker fees from GSK. MRM reports advisory board fees from Allarity Therapeutics, AstraZeneca, BioCAD, BioNTech, Boehringer Ingelheim, Clovis Oncology, Daiichi-Sankyo, Eisai, Genmab, GSK, ImmunoGen, Incyte, Karyopharm Therapeutics, MSD, Mersana Therapeutics, Novartis, Regeneron, Roche, Seagen, Takeda, Tesaro, and Zai Lab; membership on the board of directors or stockholder/shareholder in Karyopharm Therapeutics and Sera Prognostics; institutional research grants from Allarity Therapeutics, Apexigen, AstraZeneca, Boehringer Ingelheim, Clovis Oncology, GSK, Novartis, Tesaro, and Ultimovacs; and serving as a trial chair for AstraZeneca, Boehringer Ingelheim, Deciphera, Daiichi-Sankyo, GSK, MSD, Mersana Therapeutics, Nuvation Bio, and Tesaro. CCM reports personal fees for advisory boards for Clovis Oncology, GSK, ImmunoGen, and MSD. DL reports grants or contracts from Alkermes, AstraZeneca, Clovis Oncology, Corcept Therapeutics, Genmab, GSK, ImmunoGen, Incyte, MSD, Novartis, Pharma&, PharmaMar, Roche, and Seagen; consulting fees from AstraZeneca, Clovis Oncology, Corcept Therapeutics, Daiichi-Sankyo, Genmab, GSK, ImmunoGen, MSD, Novartis, Novocure, Oncoinvent, Seagen, and Sutro Biopharma; honoraria from AstraZeneca, Corcept Therapeutics, Genmab, GSK, ImmunoGen, MSD, and Seagen; support for attending meetings and/or travel from AstraZeneca, GSK, Menarini Group, and MSD; participation on a data safety monitoring board or advisory board for AstraZeneca, Clovis Oncology, Corcept Therapeutics, Daiichi-Sankyo, Genmab, GSK, ImmunoGen, MSD, Novocure, Oncoinvent, Seagen, and Sutro Biopharma; and leadership or fiduciary roles in ENGOT, GCIG, and MITO. RGM reports consulting fees from Fujirebio. GF reports honoraria from GSK. REO reports support for the present manuscript from NCI/NIH P30 CA008748; institutional contracts or grants from AbbVie/StemCentrx, Acrivon Therapeutics, Alkermes/Mural Oncology, ArsenalBio, Atara Biotherapeutics, Bayer/Celgene/Juno, Genentech, Genmab/Seagen, Gynecologic Oncology Foundation, Kite, Ludwig Cancer Institute, Lyell, Marker Therapeutics, MSD, OnCusp Therapeutics, Regeneron, Syndax, TCR2 Therapeutics, and Tesaro/GSK; payment or honoraria for lectures from Curio/OncLive/PER/MJH/Aptitude Health, GSK, Gynecologic Oncology Canada, and Society for Immunotherapy of Cancer; support for attending meetings and/or travel from Gathering Around Center Ireland, GOG Foundation, Hitech Health, and SGO; participation on a data safety monitoring board or advisory board for 2seventybio, Acrivon Therapeutics, AstraZeneca, Bayer, Carina Biotech, GSK, ImmunoGen, Link Immunotherapeutics, LOXO Oncology, Miltenyi Biotec, Mural Oncology, OnCusp Therapeutics, R Pharm US, and Seattle Genetics/Seagen/Pfizer; and leadership or fiduciary roles in NRG Oncology (Chair, Developmental Therapeutics Committee) and SGO (Vice-Chair, Clinical Practice Committee). FH reports honoraria from AstraZeneca, GSK, Roche, and Tesaro and consulting fees from AstraZeneca, GSK, ImmunoGen, Novocure, PharmaMar, Roche, Tesaro, and Zai Labs. DMO reports personal fees from AbbVie, Adaptimmune, Agenus, Arquer Diagnostics, Arcus Biosciences, AstraZeneca, Atossa Therapeutics, Boston Biomedical, Cardiff Oncology, Celcuity, Clovis Oncology, Corcept Therapeutics, Duality Bio, Eisai, Elevar Therapeutics, Exelixis, Genentech, Genelux, GSK, GOG Foundation, ImmunoGen, Imvax, InterVenn, InxMed, Iovance Biotherapeutics, Janssen, Jazz Pharmaceuticals, Laekna, Leap Therapeutics, Luzsana Biotechnology, MSD, Mersana Therapeutics, Myriad, Novartis, Novocure, OncoC4, Onconova Therapeutics, Regeneron, RepIimune, R Pharm US, Roche, Seagen, Sorrento Therapeutics, Sutro Biopharma, Tarveda Therapeutics, Toray Industries, Trillium Therapeutics Inc, Umoja Biopharma, Verastem Oncology, VBL Therapeutics, Vincerx Pharma, Xencor, Zentalis; and grants and contracts to the institution from AbbVie, Advaxis, Agenus, Alkermes, Aravive, Arcus Biosciences, AstraZeneca, Boston Biomedical, Bristol Myers Squibb, Clovis Oncology, Deciphera, Eisai, EMD Serono, Exelixis, Genentech, Genmab, GSK, GOG Foundation, ImmunoGen, Incyte, Iovance Biotherapeutics, Karyopharm Therapeutics, Leap Therapeutics, Ludwig Institute for Cancer Research, MSD, Mersana Therapeutics, NCI, Novartis, Novocure, NRG Oncology, OncoC4, OncoQuest Pharmaceuticals, Pfizer, Precision BioSciences, Prelude Therapeutics, Regeneron, Roche, RTOG Foundation, Rubius Therapeutics, Seagen, Sutro Biopharma, SWOG, Verastem Oncology. AR reports consulting fees from AstraZeneca, Boehringer Ingelheim, GSK, MSD, and Pharma&; honoraria from AstraZeneca, GSK, MSD, and Pharma&; and support for attending meetings and/or travel from AstraZeneca, GSK, and MSD. MSS reports consulting fees from AstraZeneca, GSK, ImmunoGen, and MSD; honoraria from AstraZeneca, Eisai, GSK, ImmunoGen, and MSD; and board membership for Unite for Her. CV reports medical writing support from GSK; consulting fees from Astellas, Atheneum, Bristol Myers Squibb, GSK, Janssen-Cilag, Leo Pharma, MSD, and Roche; advisory board fees from AstraZeneca, Bayer, GSK, Janssen-Cilag, Leo Pharma, MSD; and travel support from Pfizer and Roche. WHB reports consulting fees from OncoC4 and participation on a data safety monitoring board or advisory board for Imunon. CAH reports honoraria for lectures from AstraZeneca, Bristol Myers Squibb, and GSK and consultancy for AstraZeneca. DMC reports support for the present manuscript from GSK; consulting fees from AstraZeneca, Eisai, GSK, and ImmunoGen; payment or honoraria for speakers’ bureaus from AstraZeneca, Eisai, GSK, ImmunoGen, and Pfizer; support for attending meetings and/or travel from GSK; participation on a data safety monitoring board for NRG Oncology; and a leadership role on the GOG Investigator Council. CP reports honoraria for presentations from AstraZeneca, Eisai, GSK, and MSD and honoraria for participation on advisory boards from AstraZeneca, Eisai, GSK, and MSD. LLH has nothing to disclose. MJRP has nothing to disclose. PD reports consulting fees from AstraZeneca, Daiichi-Sankyo, and GSK/Tesaro. LG reports consulting fees and honoraria from AstraZeneca, Clovis Oncology, GSK, MSD, and PharmaMar; support for attending meetings and/or travel from AstraZeneca, GSK, and MSD; and participation in a data safety monitoring board or advisory board for AstraZeneca and GSK. TJH reports scientific advisory boards and/or consulting fees from Aadi Bioscience, AstraZeneca, Caris Life Sciences, Clovis Oncology, Corcept Therapeutics, Eisai, Epsilogen, Genentech, GSK, Johnson&Johnson, MSD, Mersana Therapeutics, Novocure, and Seagen. IB reports consulting fees from GSK. NC is a former employee of GSK and is currently receiving consulting fees from GSK. LS and IAM are employees of and may hold stock in GSK. AGM reports fees for different educational or advisory-related activities from Alkermes, Amgen, AstraZeneca, BioNTech, Clovis Oncology, Daiichi-Sankyo, Eisai, Genmab, GSK, Hedera Dx, ImmunoGen, Illumina, Karyopharm Therapeutics, MacroGenics, Mersana Therapeutics, MSD, Novartis, Novocure, Oncoinvent, PharmaMar, Regeneron, Roche, Seagen, Sotio, Sutro Biopharma, Takeda, and Tubulis.

Data sharing

Please refer to the GSK weblink to access GSK’s data sharing policies and as applicable seek anonymized subject-level data via the link https://www.gsk-studyregister.com/en/.

Supplementary data

Supplementary data

References

Cited by (0)

†
Present address: Johns Hopkins Hospital, Baltimore, USA.
‡
Present address: Humanitas San Pio X, Milan, Humanitas University, Pieve Emanuele (Milan), Italy.
§
Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany;
☆
Note: This study was presented at the 2024 meeting of the European Society for Medical Oncology, 13-17 September 2024, Barcelona, Spain.
© 2024 The Author(s). Published by Elsevier Ltd on behalf of European Society for Medical Oncology.

eierstokkanker, Niraparib, PARP-remmers, overall overleving, hoog risico patienten, onderhoudsbehandeling, Fase III PRIMA/ENGOT-OV26/GOG-3012 studie


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