LBA33 - ICON9: International phase III randomized study to evaluate the efficacy of maintenance therapy with olaparib and cediranib or olaparib alone in patients with relapsed platinum-sensitive ovarian cancer following a response to platinum-based chemotherapy

Background

Although many patients with recurrent ovarian cancer respond to platinum-based therapy, the duration of benefit is often short. Maintenance therapy with olaparib, a poly-ADP ribose polymerase inhibitor (PARPi), or cediranib, a vascular endothelial growth factor receptor inhibitor, prolongs progression-free survival (PFS). ICON9 investigated these agents in combination.

Methods

ICON9, an international academic phase III trial, randomised (1:1) patients with high grade platinum-sensitive recurrent ovarian cancer responding to chemotherapy to receive maintenance oral olaparib 300mg twice daily alone (O) or with cediranib 20mg once daily (O+C). Stratification was by country, tumour BRCA (tBRCA), prior bevacizumab, platinum-free interval, surgery at relapse. No prior PARPi was allowed. The primary endpoint was PFS.

Results

337 patients were randomised from 48 centres in 4 countries (Aug2018–Feb2023). Arms were well balanced, median age was 63 years (range:34–85) and 77.2% tBRCA wild-type (wt). At 37.0 months (mo) median follow-up, median PFS was 13.9 vs 11.0 mo (HR=0.84, 95%CI:0.65–1.07, p=0.24) and median OS 37.2 vs 37.8 mo (HR=0.92, 95%CI:0.67–1.25, p=0.81) in O+C and O respectively. Restricted median survival times (RMST) show that in the first 24 mo O+C had on average 1.9 mo (95%CI:0.2–3.6) more time progression-free than O (14.7 vs 12.8 mo). In the tBRCAwt group (n=260), PFS HR=0.77 (95%CI:0.58–1.01) and OS HR=0.95 (95%CI:0.67–1.35). There were more grade ≥3 adverse events with O+C (60.7% vs 36.6%); median 11 (range:0-55) and 8 (0-51) cycles of O+C or O received. Table: LBA33

Conclusions

Maintenance O+C did not improve efficacy compared to O. PARPi alone led to better than anticipated outcomes. Translational work to identify patients who might benefit most from this approach is ongoing.

Clinical trial identification

EudraCT: 2017-000161-75.

Editorial acknowledgement

Legal entity responsible for the study

University College London.

Funding

Cancer Research UK (A19714 CRUK/15/074). Supported by Stand Up To Cancer. AstraZeneca are providing trial drugs and support for international participation and translational research. Australia: supported through the Priority-driven Collaborative Cancer Research Scheme; funded by Cancer Australia (1100619) and Clinical Trials and Cohort Studies NHMRC Grant (2014936). Canada: funded by The Canadian Cancer Society.

Disclosure

S. Nicum: Financial Interests, Personal, Advisory Board: GSK, AstraZeneca, Biontech; Financial Interests, Personal, Invited Speaker: GSK, AstraZeneca, Clovis; Financial Interests, Personal, Other, scientific committee: GSK; Financial Interests, Personal, Stocks/Shares: GSK; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Research Grant: GSK. 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, Immunogen, Miltenyi, Novocure, Immagene; Financial Interests, Personal, Other, Independent Data Monitoring Committee: Mersana, Sutro Bio, Mersana; Financial Interests, Institutional, Research Grant, Clinical Research University: AstraZeneca, MSD/Merck; Non-Financial Interests, Leadership Role, ESGO Chair of the Joint IGC/ESGO journal Committee for Int J Gyn Cancer: European Society of Gynaecological Oncology; Non-Financial Interests, Officer, Chair Gynaecological Clinical Practice Guidelines ( to Dec 2023): ESMO; Non-Financial Interests, Advisory Role, Chair of the Committee: National Cancer Audit Collaborating Centre (NATCAN) ( National Ovarian Cancer Audit); Other, Associate Editor: Therapeutic Advances in Medical Oncology: Sage Publishing. L. Mileshkin: Financial Interests, Personal, Advisory Board, Participation in Dostarlimab advisory board: GSK; Financial Interests, Institutional, Coordinating PI, Institutional funding from BeiGene for an investigator-initiated trial: BeiGene; Financial Interests, Personal, Coordinating PI, Support for flights to attend ESMO meetings in Madrid and Singapore to present results of the CUPISCO trial: Roche; Financial Interests, Personal, Other, Medical writing support for publications related to the CUPISCO trial: Roche; Non-Financial Interests, Other, Co-chair of the Steering Committee for the CUPISCO trial in CUP (non-remunerated): Roche; Non-Financial Interests, Member, Member of multiple other cancer organisations as above: ASCO, MOGA, COSA, IGCS, GCIG. G.C. Jayson: Financial Interests, Personal, Advisory Board, Interview about treatment options: AstraZeneca; Financial Interests, Institutional, Coordinating PI, Funding for investigator led studies. No personal remuneration: AstraZeneca; Non-Financial Interests, Leadership Role, Coordinate Translational Research in ICON9: AstraZeneca. 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, AbbVie; Financial Interests, Personal, Writing Engagement: PeerVoice; Financial Interests, Personal, Other, IDMC: MSD; Financial Interests, Personal, Writing Engagement, Both personal and institutional: Verastem; Financial Interests, Institutional, Research Grant: AstraZeneca, Novartis, Aprea, Nucana, Medannex; Financial Interests, Institutional, Local PI: GSK, BerGenBio, MSD, Clovis, Roche, Verastem, Artios; 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. A. Michael: Financial Interests, Personal, Advisory Board: Eusa Pharma, Tesaro; Financial Interests, Personal, Invited Speaker: GSK, Ipsen, Clovis, Novartis, Pfizer; Financial Interests, Personal, Other, travel, accommodation: Merck; Financial Interests, Personal, Other, conference attendance: Ipsen; Financial Interests, Local PI: CARINA Trial, Vinehealth, OVAL-1; Financial Interests, Institutional, Local PI: MODIFY. R. Lord: Financial Interests, Personal, Advisory Board, paid advisory work: GSK; Financial Interests, Institutional, Funding, investigator led clinical trial (COMICE) financed by AstraZeneca and run through Liverpool trials unit: AstraZeneca. H. Mackay: Financial Interests, Personal, Advisory Board: Eisai, GSK, Merck; Financial Interests, Personal, Other, Associate Editor: British Journal of Cancer. M. Hall: Financial Interests, Personal, Advisory Board, Ad boards. speaker engagements: GSK; Financial Interests, Personal, Advisory Board, Ad boards: Amgen; Financial Interests, Personal, Advisory Board, Ad Boards: AZ; Financial Interests, Personal, Advisory Board, Ad Boards, speaker engagement: Clovis Oncology; Financial Interests, Institutional, Research Grant, Funding and drug for CeNtuRIOn clinical trial - Glasgow Clinical trials Unit: Clovis Oncology; Financial Interests, Institutional, Research Grant, Research funding and drugs for CeNtuRIOn clinical trial - Glasgow Clinical Trials Unit: BMS; Financial Interests, Institutional, Research Grant, Research Funding and drug for CoRinTh clinical trial - Cardiff clinical trials Unit: Merck. L. Tookman: Financial Interests, Personal, Invited Speaker, Honoraria for talks/presentations: AstraZeneca; Financial Interests, Personal, Invited Speaker, Honoraria for presentations: GSK; Financial Interests, Personal, Advisory Board, Olaparib for ovarian cancer: AstraZeneca; Financial Interests, Personal, Invited Speaker, honoraria for presentation on HRD testing: MSD; Financial Interests, Personal, Advisory Board, Dostarlimab for endometrial cancer: GSK; Financial Interests, Personal, Advisory Board, Advisory board for rucaparib (Athena clinical trial): Clovis Oncology; Financial Interests, Personal, Invited Speaker, Honoraria for talks and presentations: Clovis Oncology; Financial Interests, Steering Committee Member, endometrial real world data projectovarian cancer perspective survey: GSK; Financial Interests, Institutional, Local PI, AtTEND clinical trial: Hoffmann-La Roche; Non-Financial Interests, Advisory Role, Expert for NICE technology Appraisal for Dostarlimab: GSK; Other, Travel and congress sponsorship: MSD. S. Banerjee: Financial Interests, Personal, Advisory Board: Immunogen, Mersana, MSD, Roche, AstraZeneca, GSK, Oncxerna, Shattuck Labs, Novartis, Epsilogen, Seagen, Eisai, Regeneron, Verastem, Myriad; Financial Interests, Personal, Invited Speaker: AstraZeneca, GSK, Takeda, Medscape, Research to Practice, Peerview, Novacure, AbbVie; Financial Interests, Personal, Stocks/Shares: PerciHealth; Financial Interests, Institutional, Research Grant: AstraZeneca, GSK; Non-Financial Interests, Principal Investigator, Phase II clinical trial Global lead, ENGOTov60/GOG3052/RAMP201: Verastem; Non-Financial Interests, Principal Investigator, ENGOT-GYN1/ATARI phase II international trial (academic sponsored): AstraZeneca; Non-Financial Interests, Principal Investigator, Academic sponsored trial PI (MONITOR-UK): GSK; Non-Financial Interests, Advisory Role, Medical advisor to UK ovarian cancer charity: Ovacome Charity; Non-Financial Interests, Leadership Role, Board Member: International Cancer Foundation (ICF). Y.C. Lee: Financial Interests, Institutional, Invited Speaker, Educational events: AstraZeneca; Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Research Grant: BeiGene. L. Farrelly: Financial Interests, Institutional, Research Grant, Free drug and funding for a comparison in a trial STAMPEDE2: Novartis; Financial Interests, Institutional, Research Grant, Free drug and funding for international/translational research in ICON9: AstraZeneca. All other authors have declared no conflicts of interest.