Rucaparib maintenance for newly diagnosed advanced ovarian cancer: interim overall survival, progression-free survival, and safety at 5 years of follow-up from the phase III ATHENA-MONO/GOG-3020/ENGOT-ov45 study☆

R. S. Kristeleit; S. Ghamande; A. Lisyanskaya; A. Oaknin; E. Prendergast; Y. B. Kim; J. Fuentes Pradera; R. D. Littell; B. Gao; G. Valabrega; D. M. O’Malley; A. Dean; C. Pisano; J. Buscema; D. Provencher; F. Zagouri; L. P. Martin; H. H. Chou; F. Demirkiran; F. Ueland; A. Chudecka-Głaz; O. Yeku; M. Beiner; C. Anderson; V. Drochytek; R. N. Eskander; R. Agarwal; L. Maloney; D. Despain; C. Connor; M. Craib; D. Shih; K. Fujiwara; B. J. Monk

doi:10.1016/j.annonc.2025.10.007

Rucaparib maintenance for newly diagnosed advanced ovarian cancer: interim overall survival, progression-free survival, and safety at 5 years of follow-up from the phase III ATHENA-MONO/GOG-3020/ENGOT-ov45 study☆

R. S. Kristeleit
, S. Ghamande
, A. Lisyanskaya
, A. Oaknin
, E. Prendergast
, Y. B. Kim
, J. Fuentes Pradera
, R. D. Littell
, B. Gao
, G. Valabrega
, D. M. O’Malley
, A. Dean
, C. Pisano
, J. Buscema
, D. Provencher
, F. Zagouri
, L. P. Martin
, H. H. Chou
, F. Demirkiran
, F. Ueland

A. Chudecka-Głaz, O. Yeku, M. Beiner, C. Anderson, V. Drochytek, R. N. Eskander, R. Agarwal, L. Maloney, D. Despain, C. Connor, M. Craib, D. Shih, K. Fujiwara, B. J. Monk

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

Background: We report the long-term efficacy and safety from the multicenter, randomized, double-blind, placebo-controlled, phase III ATHENA-MONO/GOG-3020/ENGOT-ov45 (NCT03522246) study of first-line rucaparib maintenance for advanced ovarian cancer. Patients and methods: Patients were randomized 4 : 1 to oral rucaparib + intravenous (i.v.) placebo or oral + i.v. placebo. Stratification factors were homologous recombination deficiency (HRD; BRCA mutation and loss of heterozygosity status) classification, residual disease post-chemotherapy, and surgical timing. The primary endpoint was investigator-assessed progression-free survival (invPFS) in HRD and intent-to-treat (ITT) populations. Overall survival (OS) and safety were secondary endpoints. Second event of progression (PFS2) and time to first subsequent treatment (TFST) were exploratory. Interim OS and final safety analyses data cut-off was 9 March 2023. Updated invPFS, PFS2, and TFST analyses data cut-off was 5 May 2025. Results: Median invPFS follow-up was ∼59 months for both rucaparib (HRD, n = 185; ITT, n = 427) and placebo (HRD, n = 49; ITT, n = 111). invPFS was significantly longer with rucaparib versus placebo in the HRD [31.4 versus 12.0 months; hazard ratio (HR) 0.52, 95% confidence interval (CI) 0.35-0.76] and ITT (20.2 versus 9.2 months; HR 0.53, 95% CI 0.42-0.69) populations. Interim OS was immature (OS maturity: ITT 35%) with the median (95% CI) OS not reached with rucaparib and 46.2 (34.6-not reached) months with placebo for the ITT population (HR 0.83, 95% CI 0.58-1.17). ITT TFST (median 23.6 versus 12.1 months) and PFS2 (35.1 versus 26.9 months) were longer with rucaparib versus placebo. Overall, 34.6% of patients receiving rucaparib completed the 24-month treatment cap versus 17.3% receiving placebo. As of 5 May 2025, 40.0% of patients on rucaparib were still on study and in long-term follow-up. Safety remained consistent with the primary analysis. Conclusions: Rucaparib monotherapy provides significant and durable long-term benefit as first-line maintenance for patients with advanced ovarian cancer with and without HRD.

Original language	English
Pages (from-to)	217-228
Number of pages	12
Journal	Annals of Oncology
Volume	37
Issue number	2
DOIs	https://doi.org/10.1016/j.annonc.2025.10.007
State	Published - Feb 2026

Bibliographical note

Publisher Copyright:
© 2025 The Author(s). Published by Elsevier Ltd on behalf of European Society for Medical Oncology. This is an open access article under the CC BY-NC-ND license. http://creativecommons.org/licenses/by-nc-nd/4.0/

Funding

RSK reports receipt of honoraria/consultation fees from AstraZeneca, Celcuity, Clovis Oncology, Duke Street Bio, Eisai, Epsilogen, Genmab, GSK, Immunogen, InCyte, Leucid, Merck AG, MSD, pharma&, Prokarium, Seagen, Shattuck Labs, and Tubulis; travel, accommodation, and/or expenses from Epsilogen and pharma&; steering committee participation for AstraZeneca, Eisai, GSK, and Merck AG. SG reports receipt of grants/research support from Adaptimmune, AstraZeneca, Clovis Oncology, Eisai, GSK, Iovance, Merck, Pfizer, Seagen, and Sutro; honoraria/consultation fees from GSK; speaker’s bureau participation for GSK. AL reports receipt of honoraria (to institution) from AstraZeneca, Incuron, MSD, Regeneron, and Roche; research funding from AstraZeneca, Incuron, MSD, Regeneron, and Roche. AO reports receipt of payment/honoraria for consulting/advisory board roles for Agenus, AstraZeneca, Clovis Oncology, Corcept Therapeutics, Daiichi Sankyo, Deciphera Pharmaceutical, Eisai, Genmab/Pfizer, GSK, ImmunoGen/AbbVie, iTeos, Mersana Therapeutics, MSD/Merck, Novocure GmbH, PharmaMar, Shattuck Labs, and Sutro Biopharma; travel, accommodation, and/or expenses from AstraZeneca, PharmaMar, and Roche. EP reports receipt of honoraria/consultation fees from AstraZeneca. YBK reports receipt of research funding from Chong Kun Dang Pharmaceutical. JFP reports receipt of honoraria for advisory roles and speaking grants from AstraZeneca, BeiGene, Bristol, Johnson & Johnson, Pfizer, Regeneron, Roche, and Takeda; travel, accommodation, and/or expenses from Johnson & Johnson and Roche; research funding (to institution) from AstraZeneca, BeiGene, Daiichi Sankyo, Gilead Sciences, MSD, Pfizer, and Roche. GV reports receipt of honoraria/consulting fees from AstraZeneca, GSK, and MSD; travel, accommodation, and/or expenses from AstraZeneca, MSD, and PharmaMar; participation in advisory boards for AbbVie, AstraZeneca, Eisai, GSK, MSD, and Regeneron. DMO reports receipt of payment/honoraria for consulting/advisory board roles from AbbVie, AstraZeneca, Corcept Therapeutics, Duality Bio, GOG Foundation, GSK, Merck & Co, MSD, Regeneron Pharmaceuticals, Verastem Oncology, and Zentalis. AD reports consulting/advisory board roles for A2A Pharmaceuticals and Valo Therapeutics. CP reports receipt of honoraria for advisory board roles from AstraZeneca, Eisai, GSK, and MSD. JB reports receipt of honoraria from GSK; holds stock as a shareholder in Johnson & Johnson. DP reports receipt of payment/honoraria for advisory board roles from AbbVie, AstraZeneca, GSK, and Merck. FZ reports receipt of honoraria for lectures and advisory board roles for AstraZeneca, Daiichi Sankyo, GENESIS Pharma, Gilead Sciences, Lilly, MSD, Novartis, Pfizer, and Roche. LPM reports advisory board participation with Daiichi Sankyo, ImmunoGen, and Sutro Biopharma; institutional funding for clinical trial activities (to institution) from Agenus, AstraZeneca, ImmunoGen, Merck, Mersana Therapeutics, Regeneron, Sutro Biopharma, and Xencor. OY reports receipt of honoraria from Medscape; consulting/advisory board roles for Gimv, hC Bioscience, and TigaTx; stock and other ownership interests with hC Bioscience; has applications for patents pending for MUC16-Directed Antibodies and a Human Artificial Chromosomes, both for therapeutic applications. CA reports consulting/advisory board roles for AbbVie, Daiichi Sankyo, Faeth Therapeutics, Intuitive Surgical, and Sarah Cannon Research Institute; travel support from American Society of Clinical Oncology. RNE reports serving in a consulting/advisory board role for AbbVie, AstraZeneca, Clovis Oncology, Daiichi Sankyo, Eisai, Elevar Therapeutics, GSK, ImmunoGen Inc, Lilly, Mersana Therapeutics, Myriad Genetics Inc, Novocure GmbH, Nuvectis, Onconova Therapeutics, Pfizer, PMV Pharmaceuticals, and Regeneron; other financial/material support from GOG P Associate Clinical Trial Advisor. LM , DD , CC , MC , and DS report prior employment with Clovis Oncology; current employment with pharma&. KF reports receipt of grants/research funding from Clovis Oncology; honoraria/consultation fees from BioNTech, Eisai, and Genmab; speaker’s bureau participation for Takeda. BJM reports receipt of honoraria/consultation fees from AstraZeneca, BioNTech, Corcept, DSI, Eisai, Eli Lilly, Genmab/Seagen/Pfizer, GOG Foundation, GSK, Immunogen/AbbVie, Incyte, Karyopharm, Merck, Mersana, Mural/Alkermes, Myriad, Natera, Novartis, Novocure, OncoC4, Panavance, pharma&, ProfoundBio/Genmab, Regeneron, Roche/Genentech, Sutro, Tubulis, Verastem, Zentalis, and Zymeworks. All other authors have declared no conflicts of interest. This work was supported by Clovis Oncology (no grant number) and pharma and GmbH (no grant number). We thank the patients, their caregivers and families, and the study investigators for their participation and commitment to this clinical study. We thank Jen Borrow for her role of clinical operations oversight for ATHENA. Medical writing assistance (funded by pharma& Schweiz GmbH and coordinated by Susan Schade-Bijur, PhD, of pharma&) was provided by Miranda Bader-Goodman, PhD, of Ashfield MedComms, an Inizio Company, and by Gautam Bijur, PhD, formerly of Ashfield MedComms.

Funders
AstraZeneca
Clovis Oncology
Roche Canada
Johnson & Johnson
pharma and GmbH
Gautam Bijur
Incuron LLC
Chong Kun Dang Pharmaceutical
Daiichi Sankyo Company, Limited
Johnson & Johnson and Roche
BeiGene
MSD Sharp and Dohme
Pfizer
pharma& Schweiz GmbH
Gilead Sciences

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

PARP inhibitor
advanced ovarian cancer
long-term follow-up
maintenance therapy
rucaparib

ASJC Scopus subject areas

Hematology
Oncology

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10.1016/j.annonc.2025.10.007

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Dive into the research topics of 'Rucaparib maintenance for newly diagnosed advanced ovarian cancer: interim overall survival, progression-free survival, and safety at 5 years of follow-up from the phase III ATHENA-MONO/GOG-3020/ENGOT-ov45 study☆'. Together they form a unique fingerprint.

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Kristeleit, R. S., Ghamande, S., Lisyanskaya, A., Oaknin, A., Prendergast, E., Kim, Y. B., Fuentes Pradera, J., Littell, R. D., Gao, B., Valabrega, G., O’Malley, D. M., Dean, A., Pisano, C., Buscema, J., Provencher, D., Zagouri, F., Martin, L. P., Chou, H. H., Demirkiran, F., ... Monk, B. J. (2026). Rucaparib maintenance for newly diagnosed advanced ovarian cancer: interim overall survival, progression-free survival, and safety at 5 years of follow-up from the phase III ATHENA-MONO/GOG-3020/ENGOT-ov45 study☆. Annals of Oncology, 37(2), 217-228. https://doi.org/10.1016/j.annonc.2025.10.007

@article{50594c1548194c9d9dda55e234636750,

title = "Rucaparib maintenance for newly diagnosed advanced ovarian cancer: interim overall survival, progression-free survival, and safety at 5 years of follow-up from the phase III ATHENA-MONO/GOG-3020/ENGOT-ov45 study☆",

abstract = "Background: We report the long-term efficacy and safety from the multicenter, randomized, double-blind, placebo-controlled, phase III ATHENA-MONO/GOG-3020/ENGOT-ov45 (NCT03522246) study of first-line rucaparib maintenance for advanced ovarian cancer. Patients and methods: Patients were randomized 4 : 1 to oral rucaparib + intravenous (i.v.) placebo or oral + i.v. placebo. Stratification factors were homologous recombination deficiency (HRD; BRCA mutation and loss of heterozygosity status) classification, residual disease post-chemotherapy, and surgical timing. The primary endpoint was investigator-assessed progression-free survival (invPFS) in HRD and intent-to-treat (ITT) populations. Overall survival (OS) and safety were secondary endpoints. Second event of progression (PFS2) and time to first subsequent treatment (TFST) were exploratory. Interim OS and final safety analyses data cut-off was 9 March 2023. Updated invPFS, PFS2, and TFST analyses data cut-off was 5 May 2025. Results: Median invPFS follow-up was ∼59 months for both rucaparib (HRD, n = 185; ITT, n = 427) and placebo (HRD, n = 49; ITT, n = 111). invPFS was significantly longer with rucaparib versus placebo in the HRD [31.4 versus 12.0 months; hazard ratio (HR) 0.52, 95\% confidence interval (CI) 0.35-0.76] and ITT (20.2 versus 9.2 months; HR 0.53, 95\% CI 0.42-0.69) populations. Interim OS was immature (OS maturity: ITT 35\%) with the median (95\% CI) OS not reached with rucaparib and 46.2 (34.6-not reached) months with placebo for the ITT population (HR 0.83, 95\% CI 0.58-1.17). ITT TFST (median 23.6 versus 12.1 months) and PFS2 (35.1 versus 26.9 months) were longer with rucaparib versus placebo. Overall, 34.6\% of patients receiving rucaparib completed the 24-month treatment cap versus 17.3\% receiving placebo. As of 5 May 2025, 40.0\% of patients on rucaparib were still on study and in long-term follow-up. Safety remained consistent with the primary analysis. Conclusions: Rucaparib monotherapy provides significant and durable long-term benefit as first-line maintenance for patients with advanced ovarian cancer with and without HRD.",

keywords = "PARP inhibitor, advanced ovarian cancer, long-term follow-up, maintenance therapy, rucaparib",

author = "Kristeleit, \{R. S.\} and S. Ghamande and A. Lisyanskaya and A. Oaknin and E. Prendergast and Kim, \{Y. B.\} and \{Fuentes Pradera\}, J. and Littell, \{R. D.\} and B. Gao and G. Valabrega and O{\textquoteright}Malley, \{D. M.\} and A. Dean and C. Pisano and J. Buscema and D. Provencher and F. Zagouri and Martin, \{L. P.\} and Chou, \{H. H.\} and F. Demirkiran and F. Ueland and A. Chudecka-G{\l}az and O. Yeku and M. Beiner and C. Anderson and V. Drochytek and Eskander, \{R. N.\} and R. Agarwal and L. Maloney and D. Despain and C. Connor and M. Craib and D. Shih and K. Fujiwara and Monk, \{B. J.\}",

note = "Publisher Copyright: {\textcopyright} 2025 The Author(s). Published by Elsevier Ltd on behalf of European Society for Medical Oncology. This is an open access article under the CC BY-NC-ND license. http://creativecommons.org/licenses/by-nc-nd/4.0/",

year = "2026",

month = feb,

doi = "10.1016/j.annonc.2025.10.007",

language = "English",

volume = "37",

pages = "217--228",

number = "2",

}

Kristeleit, RS, Ghamande, S, Lisyanskaya, A, Oaknin, A, Prendergast, E, Kim, YB, Fuentes Pradera, J, Littell, RD, Gao, B, Valabrega, G, O’Malley, DM, Dean, A, Pisano, C, Buscema, J, Provencher, D, Zagouri, F, Martin, LP, Chou, HH, Demirkiran, F, Ueland, F, Chudecka-Głaz, A, Yeku, O, Beiner, M, Anderson, C, Drochytek, V, Eskander, RN, Agarwal, R, Maloney, L, Despain, D, Connor, C, Craib, M, Shih, D, Fujiwara, K & Monk, BJ 2026, 'Rucaparib maintenance for newly diagnosed advanced ovarian cancer: interim overall survival, progression-free survival, and safety at 5 years of follow-up from the phase III ATHENA-MONO/GOG-3020/ENGOT-ov45 study☆', Annals of Oncology, vol. 37, no. 2, pp. 217-228. https://doi.org/10.1016/j.annonc.2025.10.007

Rucaparib maintenance for newly diagnosed advanced ovarian cancer: interim overall survival, progression-free survival, and safety at 5 years of follow-up from the phase III ATHENA-MONO/GOG-3020/ENGOT-ov45 study☆. / Kristeleit, R. S.; Ghamande, S.; Lisyanskaya, A. et al.
In: Annals of Oncology, Vol. 37, No. 2, 02.2026, p. 217-228.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Rucaparib maintenance for newly diagnosed advanced ovarian cancer

T2 - interim overall survival, progression-free survival, and safety at 5 years of follow-up from the phase III ATHENA-MONO/GOG-3020/ENGOT-ov45 study☆

AU - Kristeleit, R. S.

AU - Ghamande, S.

AU - Lisyanskaya, A.

AU - Oaknin, A.

AU - Prendergast, E.

AU - Kim, Y. B.

AU - Fuentes Pradera, J.

AU - Littell, R. D.

AU - Gao, B.

AU - Valabrega, G.

AU - O’Malley, D. M.

AU - Dean, A.

AU - Pisano, C.

AU - Buscema, J.

AU - Provencher, D.

AU - Zagouri, F.

AU - Martin, L. P.

AU - Chou, H. H.

AU - Demirkiran, F.

AU - Ueland, F.

AU - Chudecka-Głaz, A.

AU - Yeku, O.

AU - Beiner, M.

AU - Anderson, C.

AU - Drochytek, V.

AU - Eskander, R. N.

AU - Agarwal, R.

AU - Maloney, L.

AU - Despain, D.

AU - Connor, C.

AU - Craib, M.

AU - Shih, D.

AU - Fujiwara, K.

AU - Monk, B. J.

N1 - Publisher Copyright: © 2025 The Author(s). Published by Elsevier Ltd on behalf of European Society for Medical Oncology. This is an open access article under the CC BY-NC-ND license. http://creativecommons.org/licenses/by-nc-nd/4.0/

PY - 2026/2

Y1 - 2026/2

N2 - Background: We report the long-term efficacy and safety from the multicenter, randomized, double-blind, placebo-controlled, phase III ATHENA-MONO/GOG-3020/ENGOT-ov45 (NCT03522246) study of first-line rucaparib maintenance for advanced ovarian cancer. Patients and methods: Patients were randomized 4 : 1 to oral rucaparib + intravenous (i.v.) placebo or oral + i.v. placebo. Stratification factors were homologous recombination deficiency (HRD; BRCA mutation and loss of heterozygosity status) classification, residual disease post-chemotherapy, and surgical timing. The primary endpoint was investigator-assessed progression-free survival (invPFS) in HRD and intent-to-treat (ITT) populations. Overall survival (OS) and safety were secondary endpoints. Second event of progression (PFS2) and time to first subsequent treatment (TFST) were exploratory. Interim OS and final safety analyses data cut-off was 9 March 2023. Updated invPFS, PFS2, and TFST analyses data cut-off was 5 May 2025. Results: Median invPFS follow-up was ∼59 months for both rucaparib (HRD, n = 185; ITT, n = 427) and placebo (HRD, n = 49; ITT, n = 111). invPFS was significantly longer with rucaparib versus placebo in the HRD [31.4 versus 12.0 months; hazard ratio (HR) 0.52, 95% confidence interval (CI) 0.35-0.76] and ITT (20.2 versus 9.2 months; HR 0.53, 95% CI 0.42-0.69) populations. Interim OS was immature (OS maturity: ITT 35%) with the median (95% CI) OS not reached with rucaparib and 46.2 (34.6-not reached) months with placebo for the ITT population (HR 0.83, 95% CI 0.58-1.17). ITT TFST (median 23.6 versus 12.1 months) and PFS2 (35.1 versus 26.9 months) were longer with rucaparib versus placebo. Overall, 34.6% of patients receiving rucaparib completed the 24-month treatment cap versus 17.3% receiving placebo. As of 5 May 2025, 40.0% of patients on rucaparib were still on study and in long-term follow-up. Safety remained consistent with the primary analysis. Conclusions: Rucaparib monotherapy provides significant and durable long-term benefit as first-line maintenance for patients with advanced ovarian cancer with and without HRD.

AB - Background: We report the long-term efficacy and safety from the multicenter, randomized, double-blind, placebo-controlled, phase III ATHENA-MONO/GOG-3020/ENGOT-ov45 (NCT03522246) study of first-line rucaparib maintenance for advanced ovarian cancer. Patients and methods: Patients were randomized 4 : 1 to oral rucaparib + intravenous (i.v.) placebo or oral + i.v. placebo. Stratification factors were homologous recombination deficiency (HRD; BRCA mutation and loss of heterozygosity status) classification, residual disease post-chemotherapy, and surgical timing. The primary endpoint was investigator-assessed progression-free survival (invPFS) in HRD and intent-to-treat (ITT) populations. Overall survival (OS) and safety were secondary endpoints. Second event of progression (PFS2) and time to first subsequent treatment (TFST) were exploratory. Interim OS and final safety analyses data cut-off was 9 March 2023. Updated invPFS, PFS2, and TFST analyses data cut-off was 5 May 2025. Results: Median invPFS follow-up was ∼59 months for both rucaparib (HRD, n = 185; ITT, n = 427) and placebo (HRD, n = 49; ITT, n = 111). invPFS was significantly longer with rucaparib versus placebo in the HRD [31.4 versus 12.0 months; hazard ratio (HR) 0.52, 95% confidence interval (CI) 0.35-0.76] and ITT (20.2 versus 9.2 months; HR 0.53, 95% CI 0.42-0.69) populations. Interim OS was immature (OS maturity: ITT 35%) with the median (95% CI) OS not reached with rucaparib and 46.2 (34.6-not reached) months with placebo for the ITT population (HR 0.83, 95% CI 0.58-1.17). ITT TFST (median 23.6 versus 12.1 months) and PFS2 (35.1 versus 26.9 months) were longer with rucaparib versus placebo. Overall, 34.6% of patients receiving rucaparib completed the 24-month treatment cap versus 17.3% receiving placebo. As of 5 May 2025, 40.0% of patients on rucaparib were still on study and in long-term follow-up. Safety remained consistent with the primary analysis. Conclusions: Rucaparib monotherapy provides significant and durable long-term benefit as first-line maintenance for patients with advanced ovarian cancer with and without HRD.

KW - PARP inhibitor

KW - advanced ovarian cancer

KW - long-term follow-up

KW - maintenance therapy

KW - rucaparib

UR - https://www.scopus.com/pages/publications/105024706061

UR - https://www.scopus.com/pages/publications/105024706061#tab=citedBy

U2 - 10.1016/j.annonc.2025.10.007

DO - 10.1016/j.annonc.2025.10.007

M3 - Article

C2 - 41115469

AN - SCOPUS:105024706061

SN - 0923-7534

VL - 37

SP - 217

EP - 228

JO - Annals of Oncology

JF - Annals of Oncology

IS - 2

ER -

Kristeleit RS, Ghamande S, Lisyanskaya A, Oaknin A, Prendergast E, Kim YB et al. Rucaparib maintenance for newly diagnosed advanced ovarian cancer: interim overall survival, progression-free survival, and safety at 5 years of follow-up from the phase III ATHENA-MONO/GOG-3020/ENGOT-ov45 study☆. Annals of Oncology. 2026 Feb;37(2):217-228. doi: 10.1016/j.annonc.2025.10.007

Rucaparib maintenance for newly diagnosed advanced ovarian cancer: interim overall survival, progression-free survival, and safety at 5 years of follow-up from the phase III ATHENA-MONO/GOG-3020/ENGOT-ov45 study☆

Abstract

Bibliographical note

Funding

UN SDGs

Keywords

ASJC Scopus subject areas

Access to Document

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