764P - How long is long enough? An international survey exploring practice variations on the recommended duration of maintenance therapy with PARP inhibitors in platinum sensitive recurrent ovarian cancer and long-term outcomes

Background

There is no consensus on the optimal duration of PARP inhibitor (PARPi) maintenance therapy for exceptional responders with platinum sensitive recurrent ovarian cancer (PS-ROC), defined as being progression-free for 5 years (yr) or longer. The current label is to continue PARPi until progression or toxicity, however practice varies internationally. The risk of late recurrence and of late onset myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML) are unknown.

Methods

An online international survey of experts from June 2023 to April 2024, disseminated at Gynaecologic Cancer Intergroup meetings and by Chairs of Cooperative Groups to select experienced members.

Results

178 responses were received from 25 countries, including Australia (n=27), the United Kingdom (21), The Netherlands (16), France (13), Canada (12), Italy (11), Japan (11), Spain (11) and others (53). Most clinicians (136, 76%) lacked guidelines regarding PARPi duration. For those with guidelines, recommendations varied: 1 yr (1), 2 yr (10), 3 yr (3), or indefinite (17). Recommendations also varied for those without guidelines: most (101, 56.7%) recommended ≥5 yr, and 33 (18.3%) recommended <5 yr. Of those recommending ≥5 yr, 62 (34.8%) recommended indefinite PARPi. 55 (30.9%) reported having patients who progressed after 5 yr of PARPi, and 37 (21.9%) reported late onset MDS/AML in patients on PARPi for >5 yr. Surveillance practices including the frequency of clinical reviews, blood tests and imaging varied substantially.

Conclusions

This survey highlights the diverse practice variations and disparate views on the optimal duration of maintenance therapy with PARPi in PS-ROC. The survey suggests a notable risk of late progression and MDS/AML among exceptional responders. Detailed individual patient data is needed to draw more reliable conclusions. A large international retrospective cohort study is underway to investigate long term outcomes of exceptional responders with PS-ROC. The results will help inform development of uniform practice guidelines.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

South Eastern Sydney Local Health District.

Funding

Has not received any funding.

Disclosure

L.R. Haggstrom: Other, Sponsorship fees for ESMO + ASCO virtual registration: Pfizer; Other, Sponsorship to attend ESMO preceptorship: ESMO; Other, Sponsorship to attend BCT Annual Scientific Meeting: Breast Cancer Trials. Y.C. Lee: Financial Interests, Personal, Invited Speaker, Educational events: AstraZeneca; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Institutional, Research Grant: BeiGene. C.L. Scott: Financial Interests, Personal, Advisory Board, Scientific Advisory Board, member, Sept 2021 - current: OncologyOne; Financial Interests, Institutional, Full or part-time Employment, Laboratory Head and Head Clinical Discovery Translation, WEHI: Walter and Eliza Hall Institute of Medical Research; Financial Interests, Institutional, Full or part-time Employment, Chair, Gynaecological Cancer: University of Melbourne; Financial Interests, Institutional, Full or part-time Employment, Specialist Medical Oncologist: Peter MacCallum Cancer Centre, Melbourne Health; Financial Interests, Institutional, Royalties, Royalties via my institution Walter and Eliza Hall Institution of Medical Research: Venetoclax; Financial Interests, Institutional, Research Grant, Research grant, PI, To my laboratory, including provision of drugs for research: AstraZeneca; Financial Interests, Institutional, Funding, Research grant, PI, To my laboratory, including provision of drug: Eisai, Sierra Oncology; Financial Interests, Institutional, Other, In kind research support including provision of drug, to my laboratory: Clovis Oncology; Financial Interests, Institutional, Other, In kind research support, provision of drug, to my laboratory: Beigene; Financial Interests, Institutional, Coordinating PI, Funding of the SOLACE2 trial, Study Chair and PI, Steering committee, Chair: AstraZeneca; Financial Interests, Institutional, Coordinating PI, Provision of study drug, Eribulin, for the EPOCH trial, Study Chair: Eisai; Financial Interests, Institutional, Coordinating PI, Provision of study drug, Pembrolizumab, for the EPOCH trial, Study Chair: MSD; Financial Interests, Institutional, Steering Committee Member, EMBRACE clinical trial, AZ supplied olaparib, My role, member of the steering committee; performing translation (funds from govt grant): AstraZeneca; Financial Interests, Institutional, Funding, Research grant, To my laboratory, including provision of drug for research: Boehringer Ingelheim; Financial Interests, Institutional, Research Grant, Research grant, PI, to my laboratory, including provision of drug: Ideaya Biosciences; Non-Financial Interests, Advisory Role, Advisory Boards, member: AstraZeneca; Non-Financial Interests, Advisory Role, Advisory Board, Member: Eisai; Non-Financial Interests, Advisory Role, Advisory Board, member: Sierra Oncology, Roche, Takeda, MSD, GSK; Non-Financial Interests, Advisory Role, Advisory Board, Chair: EpsilaBio; Non-Financial Interests, Institutional, Proprietary Information, Research collaboration, provision of drugs and discussion of commercial in confidence information: AstraZeneca, Eisai; Non-Financial Interests, Institutional, Product Samples, Research collaboration, provision of drugs: AstraZeneca, Eisai; Non-Financial Interests, Institutional, Proprietary Information, Research collaboration, provision of drugs: Boerhinger Ingelheim, Ideaya Biosciences; Non-Financial Interests, Other, Board, Chair: International Rare Cancer Initiative; Non-Financial Interests, Leadership Role, GCIG Executive Board of Directors, Member: Gynaecological Cancer InterGroup (GCIG), Director; Other, PI, funded by theAustralian Government as part of the Australian Genomic Cancer Medicine Centre (AGCMC) (OMICO).: Australian Rare Cancer Portal. J.A. Ledermann: Financial Interests, Personal, Advisory Board, Advisory Board and Speaker Fees: AstraZeneca, Clovis Oncology, GSK; Financial Interests, Personal, Advisory Board: Artios Pharma, Eisai, Merck/MSD, VBL Therapeutics, Bristol Myers Squibb, Nuvation, Ellipses, ImmunoGen, Miltenyi, Novocure, Immagene; Financial Interests, Personal, Invited Speaker, Speaker Fees: Neopharm; Financial Interests, Personal, Other, Independent Data Monitoring Committee: Mersana; Financial Interests, Personal, Other, IDMC: Sutro Bio, Mersana; Financial Interests, Institutional, Research Grant, Clinical Research University: AstraZeneca, MSD/Merck; Non-Financial Interests, Leadership Role, Vice President ( 2019-2021): European Society of Gynaecological Oncology; Non-Financial Interests, Officer, Chair Gynaecological Clinical Practice Guidelines: ESMO; Other, Associate Editor: Therapeutic Advances in Medical Oncology: Sage Publishing. C. Gourley: Financial Interests, Personal, Invited Speaker, Both personal and institutional: Roche, AstraZeneca, MSD, GSK, Clovis, Chugai, Takeda, Eisai; Financial Interests, Personal, Advisory Board, Both personal and institutional: AstraZeneca, MSD, GSK; Financial Interests, Personal, Writing Engagement: Cor2Ed, PeerVoice; Financial Interests, Personal, Other, IDMC: MSD; Financial Interests, Institutional, Research Grant: AstraZeneca, Novartis, Aprea, Nucana, Medannex; Financial Interests, Institutional, Local PI: GSK, BerGenBio, MSD, Clovis, Roche, Verastem; Non-Financial Interests, Other, Committee member: Cancer Research UK Clinical Research Committee; Non-Financial Interests, Other, Committee Member: German Cancer Aid Scientific Review Committee, International Clinical Cancer Research Committee, Institut National du Cancer, France. I. McNeish: Financial Interests, Personal, Advisory Board, Advisory Boards and travel: AstraZeneca, GSK; Financial Interests, Personal, Advisory Board: Roche, Alkermes, OncoC4, Theolytics; Financial Interests, Personal, Advisory Board, Advisory and consultancy on development of novel therapeutics in ovarian cancer: Duke Street Bio; Financial Interests, Personal, Advisory Board, Advice ahead of NICE submission: Pharma&; Financial Interests, Personal, Advisory Board, Advisory Board: BioNTech; Financial Interests, Institutional, Funding: AstraZeneca; Non-Financial Interests, Member of Board of Directors, Trustee of this charity: Worldwide Cancer Research. F. Amant: Financial Interests, Institutional, Advisory Board: MiMARK Diagnostics; Financial Interests, Institutional, Funding: Estée Lauder. I.L. Ray-Coquard: Financial Interests, Personal, Advisory Board: Roche, GSK, AstraZeneca, Mersana, Deciphera, Amgen, Oxnea, Merck Sereno, Agenus, Novartis, Macrogenics, Clovis, EQRX, adaptimmun, Eisai, SUTRO, BMS, Adaptimmune, Daichi-Santyo, ImmunoGen, Seagen, PMV Pharma; Financial Interests, Institutional, Other, COLIBRI translational research: BMS; Financial Interests, Institutional, Advisory Board, translational research NEOPREMBROV trial: MSD; Non-Financial Interests, Principal Investigator: PAOLA1; Non-Financial Interests, Other, President: GINECO. A. Leary: Financial Interests, Personal, Advisory Board: Zentalis; Financial Interests, Personal, Invited Speaker, Educational: GSK, Medscape; Financial Interests, Personal, Writing Engagement, Educational: Onko+; Financial Interests, Institutional, Other, Steering committee: MSD; Financial Interests, Institutional, Advisory Board: GSK, AZ, Clovis, Ability Pharma, MSD, Merck Serono, Apmonia, Blueprint; Financial Interests, Institutional, Invited Speaker, Educational: Kephren publishing; Financial Interests, Institutional, Other, Consultancy: Orion; Financial Interests, Institutional, Invited Speaker: AZ, Clovis; Financial Interests, Personal, Other, Consultancy: GLG; Financial Interests, Institutional, Other, consultancy: OWKIN; Financial Interests, Institutional, Research Grant, PI translational research: ARCAGY-GINECO, Sanofi, AZ; Financial Interests, Institutional, Funding, CI clinical trial: AZ; Financial Interests, Institutional, Research Grant, Int CI clinical trial: OSE immuno; Financial Interests, Institutional, Funding, PI clinical trial: Agenus, BMS, Iovance, GSK; Financial Interests, Institutional, Funding, PI 5 clinical trials: Roche; Financial Interests, Institutional, Funding, PI 2 clinical trials: AZ; Financial Interests, Institutional, Funding, PI 3 clinical trials and steering committee: MSD; Non-Financial Interests, Institutional, Other, Academic research project: Owkin, LXRepair; Non-Financial Interests, Personal, Proprietary Information, IDMC member: Clovis; Non-Financial Interests, Personal, Proprietary Information, IDMC chair: Pfizer; Non-Financial Interests, Member: GCIG. A.M. Oza: Financial Interests, Personal, Advisory Board: Morphosys, AstraZeneca, BMS; Non-Financial Interests, Personal, Leadership Role, CEO and Board Member: Ozmosis Research. A. Tinker: Financial Interests, Personal, Advisory Board: GSK, AstraZeneca, Eisai, Merck. A. González-Martín: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Clovis, GSK, Genmab, Alkermes, Sutro, Roche, Sotio, PharmaMar, Oncoinvent, Novartis, Mersana, MSD, Macrogenics, Eisai, Inmunogen, Regeneron, HederaDx, Illumina, Tubulis; Financial Interests, Personal, Invited Speaker: GSK, AstraZeneca, Clovis, Roche, Novocure, MSD, Takeda, Zaylab; Financial Interests, Institutional, Coordinating PI, PI of ANITA trial: GSK, Roche; Financial Interests, Personal, Steering Committee Member, Member of ENGOT ov43-SC: MSD; Financial Interests, Institutional, Coordinating PI, ENGOT PI of EPIK-O trial: Novartis; Financial Interests, Institutional, Coordinating PI, ENGOT PI of AVB-500 phase III trial: ARAVIVE. S.C. Cecere: Financial Interests, Personal, Other, Honoraria: AstraZeneca, MSD, PharmaMar. N. Colombo: Financial Interests, Personal, Advisory Board, Various: Roche, AstraZeneca, MSD/Merck, Clovis Oncology, GSK, ImmunoGen, Mersana; Financial Interests, Personal, Invited Speaker, Congress, Symposia, Lectures: AstraZeneca; Financial Interests, Personal, Advisory Board, Lectures: Eisai; Financial Interests, Personal, Advisory Board, Advisory role: Nuvation Bio, Pieris; Financial Interests, Personal, Advisory Board, Advisory Role: Onxerna; Financial Interests, Personal, Invited Speaker: MSD/MERCK; Financial Interests, Personal, Invited Speaker, Speaker: GSK; Financial Interests, Personal, Advisory Board: Novocure, BioNTech; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche, GSK; Non-Financial Interests, Leadership Role, Chair, Scientific Committee: ACTO (Alleanza contro il tumore ovarico). C. Marth: Financial Interests, Personal, Advisory Board: AstraZeneca, Roche Austria, Novartis, MSD, PharmaMar, GSK, Pfizer, ImmunoGen, Daiichi Sankyo, Biontech, Novocure, Eisai; Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche, GSK, Novartis, MSD, PharmaMar, Roche, AstraZeneca, GSK; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche. D.S. Tan: Financial Interests, Personal, Invited Speaker: AstraZeneca, MSD, Merck Serono, Roche, Eisai, GSK, Takeda; Financial Interests, Personal, Advisory Board: AstraZeneca, Bayer, MSD, Eisai, Roche, Genmab, GSK, Boehringer Ingelheim; Financial Interests, Personal, Stocks/Shares: Asian Microbiome Library (AMiLi); Financial Interests, Institutional, Research Grant: Roche, Bayer, Karyopharm Therapeutics, AstraZeneca; Financial Interests, Institutional, Coordinating PI: AstraZeneca, Bergen Bio; Financial Interests, Institutional, Local PI: Zeria Pharmaceutical Co Ltd, Bayer, Byondis B.V.; Non-Financial Interests, Leadership Role, Ex society president: Gynecologic Cancer Group Singapore; Non-Financial Interests, Member of Board of Directors: Gynaecologic Cancer Intergroup (GCIG); Non-Financial Interests, Leadership Role, Ex- Chair: Asia-Pacific Gynecologic Oncology Trials Group (APGOT); Non-Financial Interests, Institutional, Product Samples, Research Study: MSD, Eisai, AstraZeneca, Cyclacel Pharmaceuticals. K.N. Moore: Financial Interests, Personal, Advisory Board: AstraZeneca, Aravive, Alkemeres, Blueprint Pharma, Eisai, EMD Serono, GSK/Tesaro, Genentech/Roche, Hengrui, Immunogen, IMab, Mereo, Myriad, Caris, Mersana, Novartis, Novocure, OncXerna, OncoNova, Tarveda, VBL Therapeutics, Clovis, Caris, Lilly, Novartis, Pannavance, Verastem, Zentalis, Merck; Financial Interests, Institutional, Advisory Board, advisory board work for gynecologic trial: Aadi; Financial Interests, Institutional, Advisory Board, work on clinical trial and planning for next trial: duality; Financial Interests, Personal, Full or part-time Employment: GOG Partners Associate Director; Financial Interests, Institutional, Full or part-time Employment: NRG Ovarian Cancer Chair; Financial Interests, Personal, Member of Board of Directors, not reimbursed: ASCO; Financial Interests, Institutional, Member of Board of Directors, not reimbursed: GOG Foundation; Financial Interests, Personal, Royalties: UP to Date; Financial Interests, Institutional, Coordinating PI, international CO-PI, local site PI: AstraZeneca; Financial Interests, Institutional, Coordinating PI: ImmunoGen, GSK/Tesaro, PTC Therapeutics, duality; Financial Interests, Institutional, Local PI: Lilly, Daiichi Sankyo, Regeneron, Artios, Bolt, Verastem; Non-Financial Interests, Member of Board of Directors: GOG. M.L. Friedlander: Financial Interests, Personal, Advisory Board: AstraZeneca, GSK, MSD, Takeda; Financial Interests, Personal, Invited Speaker: Limbic; Financial Interests, Institutional, Funding: AstraZeneca, Novartis, BeiGene; Non-Financial Interests, Personal and Institutional, Principal Investigator: AstraZeneca, BeiGene. All other authors have declared no conflicts of interest.