How long is long enough? An international survey exploring practice variations on the recommended duration of maintenance therapy with PARP inhibitors in patients with platinum sensitive recurrent ovarian cancer and long-term outcomes.

Objective: There are no data, and thus no consensus, on the optimal duration of poly(ADP-ribose) polymerase (PARP) inhibitor maintenance therapy for exceptional responders (here defined as progression-free for 5 years or longer) with platinum sensitive recurrent ovarian cancer. The current licence is to continue PARP inhibitors until progression or toxicity; however, international practice varies considerably. The risks of late progression and late-onset myeloid malignancies, defined as occurring beyond 5 years of PARP inhibition, are unknown. This study aims to examine the practice patterns and opinions regarding the management and surveillance protocols of exceptional responders with platinum sensitive recurrent ovarian cancer.
Methods: An online international survey of experts from June 2023 to June 2024 was carried out, disseminated at Gynaecologic Cancer Intergroup meetings and by Chairs of Cooperative Groups.
Results: 210 responses were received from 26 countries including Australia (27 respondents), Germany (24), the UK (21), the Netherlands (16), France (13), Spain (12), Canada (12), Italy (11), Japan (11), and other countries (63). Most respondents did not have institutional or trials group guidelines regarding duration of PARP inhibitors (154, 73.3%). For the minority with guidelines, recommendations varied: 1 year (2), 2 years (13), 3 years (4), and indefinite treatment (22). Individual practice varied considerably for those without guidelines: most (116, 76.3%) recommended ≥5 years of PARP inhibition, of which 73 (48.0%) recommended indefinite PARP inhibition. Sixty-six respondents (31.4%) reported having patients with late progression and 46 (22.0%) had cases with late-onset myeloid malignancies. Surveillance practices varied widely across all respondents.
Conclusions: This international survey highlights the diverse practice variations and disparate views on the optimal duration of maintenance therapy with PARP inhibitors in platinum sensitive recurrent ovarian cancer. The responses suggest a notable risk of late progression and myelodysplastic syndrome/acute myeloid leukemia among exceptional responders which needs confirmation. Detailed individual patient data is required to draw more reliable conclusions; another study is underway addressing this.
Competing Interests: Competing interests: The authors have the following relevant disclosures within the last 36 months: AGM: honoraria from AstraZeneca, GlaxoSmithKline, Clovis, Roche, Novocure, MSD, Takeda, Zaylab; travel support from AstraZeneca, GSK and MSD; participation on a Data Safety Monitoring Board or Advisory Board for Alkermes, AstraZeneca, Amgen, Clovis, Eisai, GlaxoSmithKline, Immunogen, GenMab, Kartos, Sutro, Roche, Sotio, Macrogenics, Mersana, MSD, Pharmamar, Novartis, Oncoinvent, Regeneron, HederaDx, Illumina, Tubulis, Daiichi Sakyo, Incyte, Novocure, BionTech and other institutional financial or non-financial interests from GSK and Roche. AL: institutional funding from GSK, MSD, AstraZeneca, Immunogen, Owkin, Oseimmuno, Incyte, Adaptimmune, Eisai, Zentalis; consulting fees from MSD, GSK, AstraZeneca, Zentalis, Apmonia, Daiichi, Owkin, Immunogen, Incite, Genmab (payments for these to institution); honoraria from GSK, MSD, AstraZeneca and Servier; travel support from Oseimmuno, AstraZeneca and GSK; participation on a Data Safety Monitoring Board or Advisory Board for Pfizer; leadership role in GINECO; member of strategic committee in GCIG, ENGOT member and ESMO track chair/faculty. AO: grants from AstraZeneca and Amgen; consulting fees from BMS; participation on a Data Safety Monitoring Board or Advisory Board for AstraZeneca and GSK, Steering Committee for AstraZeneca and GSK; and Principal Investigator of investigator initiated trials for AstraZeneca and GSK. AT: honoraria from GSK and AstraZeneca; travel support from GSK. CM: funded research: EU, FWF, AstraZeneca, Roche; honoraria/expenses from Roche, Novartis, MSD, Pharmamar, AstraZeneca, GSK and Consulting/Advisory Board for Roche, Novartis, MSD, AstraZeneca, Pfizer, Pharmamar, ImmunoGen, Daiichi Sankyo, Biontech, Novocure, Eisai, GSK, Abbvie, and Seagen. CG: manuscript support, grants, and contracts from AstraZeneca, GlaxoSmithKline, Tesaro, Clovis, MSD, BergenBio, Novartis, Aprea, Artios, Verastem, Roche, and Medannex; consulting fees from AstraZeneca, MSD, GlaxoSmithKline, and Verastem; honoraria for lectures and presentations from AstraZeneca, MSD, GlaxoSmithKline, Tesaro, Clovis, Roche, Nucana, Chugai, Takeda, Cor2Ed, and Peervoice; advisory board attendance from AstraZeneca, MSD, GlaxoSmithKline, Tesaro, Roche, Nucana, Chugai, and Verastem; Committee Member for the Scottish Medicines Consortium. CS: grant and research support from Clovis Oncology, Eisai Inc, Sierra Oncology, Roche, Beigene, AstraZeneca; membership on Advisory boards: AstraZeneca, Clovis Oncology, Roche, Eisai, Sierra Oncology, Takeda, MSD; committee membership on GCIG, IRCI (Chair), ANZGOG (Chair). DT: research funding from the National Medical Research Council (NMRC) Clinician Scientist Award Senior Investigator Grant (CSASI21jun-0003), the Pangestu Family Foundation Gynaecological Cancer Research Fund, and product samples from AstraZeneca, Eisai, and MSD (non-financial interest) for research trials; institutional research grants from AstraZeneca, Bayer, Karyopharm Therapeutics, and Roche; personal fees for advisory board membership from AstraZeneca, Bayer, BioNTech, Boehringer Ingelheim, Eisai, Genmab, GSK, MSD, PMV Pharma, Daiichi Sankyo and Roche; personal fees as an invited speaker from AstraZeneca, Eisai, GSK, Merck Serono, MSD, Roche, and Takeda; travel support from AstraZeneca, Eisai, GSK, Merck Serono, MSD, Roche, and Takeda; current non-renumerated role as protocol chair of Asia Pacific Gynecologic Oncology Trials Group (APGOT); previous non-renumerated role as Chair of the Asia Pacific Gynecologic Oncology Trials Group (APGOT); a previous non-renumerated role as the Society President of the Gynecologic Cancer Group Singapore; non-renumerated membership of the Board of Directors of the GCIG, and ownership of stocks/shares of Asian Microbiome Library (AMiLi). FA: participation on Advisory Board for MiMark. IM: consulting fees from AstraZeneca, Bicycle Therapeutics, Clovis Oncology/pharma, Duke Street Bio, Epsila Bio, Roche, Scancell, GSK, Theolytics, Transgene Biotek, and OncoC4; honoraria from GSK; participation on a Data Safety Monitoring Board or Advisory Board for Roche; unpaid trustee of Worldwide Cancer Research (charity). IRC: grants/contracts from AstraZeneca, Clovis, GSK, Mersana, BMS and MSD; honoraria from AstraZeneca, Clovis, GSK, Mersana, BMS and MSD, Roche, Pharmamar, Seagen, Eisai, Novartis; travel support from Roche, GSK, AstraZeneca, Pharmamar, MSD; participation on a Data Safety Monitoring Board or Advisory Board for Clovis, Deciphera, Adaptimmune, Sutro, Immunogen. JL: grants from AstraZeneca, Merck/MSD; consulting fees from AstraZeneca, Clovis Oncology, GSK, Artios Pharma, Merck/MSD, VBL Therapeutics, Bristol Myers Squibb, Nuvation, Immagene, Incyte, Immunogen/Abbvie, Novocure; honoraria from AstraZeneca, MSD/Merck, Clovis Oncology, GSK; participation on a Data Safety Monitoring Board or Advisory Board for Mersana and SutroBio; Editor for ESMO Clinical Practice Guidelines – Gynaecological Cancer until December 2023; Past Vice President ESGO until 2021; Chair of National Ovarian Cancer Audit Committee. EMG-G: honoraria and travel support from AstraZeneca, Amgen, Merck and Eisai; participation on a Data Safety Monitoring Board or Advisory Board for Merck, AstraZeneca and Roche. HY: no relevant disclosures. KM: grants/contracts from PTC Therapeutics, Lilly, Clovis, Genentech, GSK, Verastem (all institutional); royalties or licenses from UptoDate; consulting fees from AstraZeneca, Aravive, Aadi, Blueprint pharma, Clovis, Caris, Duality, Eisai, GSK, Genentech/Roche, Hengrui, Immunogen, Iovance, Janssen, Lilly, Mereo, Mersana, Merck, Myriad, Novartis, Novocure, Pannavance, Onconova, VBL Therapeutics, Verastem, Zentalis; honoraria from AstraZeneca, GSK, Immunogen, PRIME, RTP, Medscape, Great Debates and Updates; travel support from AstraZeneca, BioNTech, GOG P Associate Director. LH: support from Pfizer for meeting registration fees. LW: grants/contracts from Seagen, MSD, Roche, Gilead, German Cancer Aid and AstraZeneca (all institutional); consulting fees from Pfizer, MSD, Roche, Seagen, Eisai, GSK, Myriad and AstraZeneca; honoraria from Pfizer, MSD, Roche, Seagen, Eisai, GSK, Novartis and AstraZeneca; travel support from AstraZeneca; participation on a Data Safety Monitoring Board or Advisory Board for MSD, Roche, Seagen/Pfizer, Eisai, GSK and Myriad; leadership roles in German Vulva Cancer Group and current President of the European College for the Study of Vulval Disease. MF: consulting fees from AstraZeneca, Novartis, GSK, Incyclix; honoraria from AstraZeneca, GSK, MSD and The Limbic; participation on a Data Safety Monitoring Board or Advisory Board for AGITG IDSMB, ENDO-3; institutional research grants from AstraZeneca, Beigene and Novartis. NC: grants from AstraZeneca, PharmaMar and Roche; honoraria from AstraZeneca and Novartis; participation on a Data Safety Monitoring Board or Advisory Board for AstraZeneca, Clovis Oncology, Eisai, GSK, ImmunoGen, Mersana, MSD/Merck, Nuvation Bio, Onxerna, Pfizer, PharmaMar, Pieris and Roche, Novocure; membership of the ESMO Guidelines Steering Committee; leadership role as Chair of the Alleanza Control il Tumore Ovarico (ACTO) Scientific Committee. OR: consulting fees from AstraZeneca, MSD, Medison, Neopharm; travel support from AstraZeneca and MSD; honoraria from AstraZeneca. PH: grants from AstraZeneca, Roche, GlaxoSmithKline, Genmab, Immunogen, Seagen, Clovis, Novartis; consulting fees from Miltenyi; honoraria from Amgen, AstraZeneca, GSK, Roche, Immunogen, Sotio, Stryker, Zai Lab, MSD, Clovis, Eisai, Mersana, Exscientia, Daiichi Sankyo, Karyopharm; travel support from AstraZeneca; participation on a Data Safety Monitoring Board or Advisory Board for AstraZeneca, Roche, GlaxoSmithKline, Clovis, Immunogen, MSD, Miltenyi, Novartis, Eisai. SCC: meeting/travel support from AstraZeneca, MSD and GSK; participation on a Data Safety Monitoring Board or Advisory Board for AstraZeneca, MSD and GSK. SP: research funding from MSD, Roche, AstraZeneca, GSK, Pfizer and honoraria from MSD, AstraZeneca, GSK, Novartis, Pfizer, Pharmamar and Roche. YCL: institutional research grant from BeiGene; honoraria from AstraZeneca; participation on Advisory Board for AstraZeneca.
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