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Proffered Paper session: Gynaecological cancers

518O - Overall survival results from ARIEL4: A phase III study assessing rucaparib vs chemotherapy in patients with advanced, relapsed ovarian carcinoma and a deleterious BRCA1/2 mutation

Date

09 Sep 2022

Session

Proffered Paper session: Gynaecological cancers

Topics

Clinical Research;  Targeted Therapy

Tumour Site

Ovarian Cancer

Presenters

Amit Oza

Citation

Annals of Oncology (2022) 33 (suppl_7): S235-S282. 10.1016/annonc/annonc1054

Authors

A.M. Oza1, A.S. Lisyanskaya2, A.A. Fedenko3, A.C. de Melo4, Y. Shparik5, I. Bondarenko6, N. Colombo7, D. Lorusso8, D. Cibula9, R.L. Póka10, A. Oaknin11, T. Safra12, B. Maćkowiak-Matejczyk13, L. Ma14, D. Thomas15, K.K. LIN16, K. McLachlan17, S. Goble18, R. Kristeleit19

Author affiliations

  • 1 Division Of Medical Oncology And Hematology, Princess Margaret Cancer Centre, University Health Network, M5G 2M9 - Toronto/CA
  • 2 Oncogynecological Department, Saint Petersburg City Oncological Dispensary, 197341 - Saint Petersburg/RU
  • 3 Department Of Chemotherapy, N.N. Blokhin Russian Cancer Research Center, 125284 - Moscow/RU
  • 4 Clinical Research Division, Instituto Nacional de Câncer - Hospital do Câncer II, 20230-130 - Rio de Janeiro/BR
  • 5 Department Of Chemotherapy, Lviv Regional Oncology Dispensary, 79000 - Lviv/UA
  • 6 Oncology And Medical Radiology Department, Dnipropetrovsk Medical Academy, Dnipro/UA
  • 7 Gynecologic Cancer Program, University of Milan-Bicocca and European Institute of Oncology (IEO) IRCCS, 20141 - Milan/IT
  • 8 Mito And Gynecologic Oncology Unit, Fondazione Policlinico Universitario Gemelli IRCCS and Catholic University of Sacred Heart, Rome/IT
  • 9 Department Of Obstetrics And Gynecology, First Faculty of Medicine, Charles University and General University Hospital, 121 11 - Prague/CZ
  • 10 Department Of Obstetrics And Gynecology, Clinical Center, University of Debrecen, 4032 - Debrecen/HU
  • 11 Gynaecologic Cancer Programme, Vall d'Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d’Hebron, Vall d’Hebron Barcelona Hospital Campus, 8035 - Barcelona/ES
  • 12 Oncology Department, Tel Aviv Medical Center, and Sackler Faculty of Medicine, Tel Aviv University, 64239 - Tel Aviv/IL
  • 13 Department Of Gynecologic Oncology, Bialostockie Centrum Onkologii im. Marii Sklodowskiej-Curie,, Białostockie/PL
  • 14 Medical Oncology, Rocky Mountain Cancer Centers, Lakewood/US
  • 15 Clinical Operations, Clovis Oncology, Inc., Boulder/US
  • 16 Molecular Diagnostics And Translational Medicine, Clovis Oncology, Inc., Boulder/US
  • 17 Clinical Development, Clovis Oncology, Inc., 80301 - Boulder/US
  • 18 Biostatistics, Clovis Oncology, Inc., Boulder/US
  • 19 Department Of Oncology, Guy’s and St Thomas’ NHS Foundation Trust, SE11 4TX - London/GB
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Resources

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Abstract 518O

Background

In the primary analysis of ARIEL4 (NCT02855944), rucaparib significantly improved progression-free survival (PFS) vs standard-of-care chemotherapy (CT) in patients (pts) with relapsed, heavily pretreated, BRCA1/2-mutated ovarian carcinoma (Kristeleit et al. Lancet Oncol. 2022;23:465-78). Here, we present final overall survival (OS) and PFS on the subsequent line of therapy (PFS2) results from the intent-to-treat (ITT) population.

Methods

Pts were randomised 2:1 to oral rucaparib 600 mg BID or CT. In the CT group, pts with progression-free interval (PFI) ≥1 to <6 months (platinum resistant) or ≥6 to <12 months (partially platinum sensitive) received weekly paclitaxel; pts with PFI ≥12 months (fully platinum sensitive) received investigator’s choice of platinum-based CT (single-agent platinum or platinum doublet). Pts in the CT group could cross over to receive rucaparib upon confirmed radiographic progression per RECIST. OS was a standalone secondary endpoint; PFS2 was an exploratory endpoint.

Results

At data cutoff, 14/233 (6%) pts in the rucaparib group and 0/116 in the CT group were ongoing on assigned study treatment. Following progression on CT, 80 (69%) pts crossed over to receive rucaparib; overall, 313/349 (90%) pts received rucaparib from randomisation or after crossover. Death events have occurred in 244 (70%) pts. Efficacy endpoints are presented in the Table. Rucaparib safety was consistent with previous reports. Table: 518O

n PFS HR (95% CI)* PFS2 HR (95% CI) Median OS, mo OS HR (95% CI)
ITT
Rucaparib 233 0.665 (0.516–0.858); P=0.002 0.860 (0.674–1.098) 19.4 1.313 (0.999–1.725)
CT 116 25.4
ITT, excluding pts who crossed over to rucaparib
Rucaparib 233 NA NA 19.4 0.423 (0.276–0.650)
CT 36 9.1
ITT, censoring pts who crossed over to rucaparib
Rucaparib 233 NA NA 19.4 1.059 (0.688–1.630)
CT 116 26.2
Platinum-sensitive
Rucaparib 113 0.502 (0.343–0.733); P=0.0004 0.737 (0.512–1.060) 29.4 1.071 (0.709–1.618)
CT 57 27.6
Platinum-resistant
Rucaparib 120 0.821 (0.583–1.155); P=0.257 0.968 (0.697–1.344) 14.2 1.511 (1.053–2.170)
CT 59 22.2

HR, hazard ratio; NA, not analysed. *Data cutoff: 30 Sep 2020; †Data cutoff: 10 Apr 2022.

Conclusions

PFS2 was not significantly different for pts in the rucaparib or CT groups. In the ITT population, the secondary endpoint of OS favoured CT. Amongst patients with platinum-sensitive disease, OS was similar between the treatment groups; the difference in the ITT population was driven by the platinum-resistant subgroup. OS was confounded by the high rate of crossover, raising important questions about the optimal sequencing of PARP inhibitors in advanced disease.

Clinical trial identification

NCT02855944 August 4, 2016.

Editorial acknowledgement

Medical writing and editorial support were funded by Clovis Oncology, Inc. and provided by Shelly Lim and Kathleen Blake of Ashfield MedComms, an Ashfield Health company.

Legal entity responsible for the study

Clovis Oncology, Inc.

Funding

Clovis Oncology, Inc.

Disclosure

A.M. Oza: Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Advisory Board: AstraZeneca, Clovis Oncology, Inc., GlaxoSmithKline; Financial Interests, Personal and Institutional, Principal Investigator: AstraZeneca, Clovis Oncology, Inc., GlaxoSmithKline. A.A. Fedenko: Financial Interests, Personal, Invited Speaker: MSD, Amgen; Financial Interests, Personal, Advisory Board: Novartis. A.C. de Melo: Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol-Myers Squibb, F. Hoffmann-La Roche, GlaxoSmithKline, Merck Sharp and Dohme; Financial Interests, Personal, Invited Speaker: AstraZeneca, Bristol-Myers Squibb, F. Hoffmann-La Roche, GlaxoSmithKline, Merck Sharp and Dohme, Novartis, Sanofi; Financial Interests, Institutional, Invited Speaker: Regeneron Pharmaceuticals, Novartis, Merck Sharp and Dohme, GlaxoSmithKline, F. Hoffmann-La Roche, Clovis Oncology, Inc., Bristol-Myers Squibb, AstraZeneca, Amgen. Y. Shparik: Financial Interests, Personal, Other, honoraria: AstraZeneca, Merck Sharp & Dohme; Financial Interests, Other, honoraria: Roche. N. Colombo: Financial Interests, Personal, Advisory Board, Various: Roche, PharmaMar, AstraZeneca, MSD/Merck, Clovis Oncology, Tesaro, GSK, Pfizer, Takeda, BIOCAD, ImmunoGen, Mersana; Financial Interests, Personal, Invited Speaker, Congress, Symposia, Lectures: AstraZeneca, Tesaro; Financial Interests, Personal, Invited Speaker, Lectures: Novartis; 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, Institutional, Research Grant: AstraZeneca, PharmaMar, Roche; Non-Financial Interests, Other, Sterring committee member Clinical Guidelines: ESMO; Non-Financial Interests, Leadership Role, Chair, Scientific Committee: ACTO( Alleanza contro il tumore ovarico). D. Lorusso: Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speaker: GSK, Clovis Oncology, PharmaMar; Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speakers: AstraZeneca, MSD; Financial Interests, Personal, Other, Consultancy: PharmaMar, Amgen, AstraZeneca, Clovis Oncology, GSK, MSD, ImmunoGen, Genmab, Seagen; Financial Interests, Personal, Advisory Board, Participation in Advisory Boards: Merck Serono; Financial Interests, Personal, Advisory Board, Invited member of advisory board: Seagen, ImmunoGen, Genmab, Oncoinvest, Corcept, Sutro; Financial Interests, Institutional, Funding, Grant for founding accdemic trial: MSD, Clovis Oncology, PharmaMar; Financial Interests, Institutional, Funding, Grant for founding acamemic trial: GSK; Financial Interests, Institutional, Invited Speaker, ENGOT trial with institutional support for coordination: Clovis Oncology; Financial Interests, Institutional, Invited Speaker, ENGOT trial with insitutional support for coordination: Genmab, MSD; Financial Interests, Institutional, Funding, Clnical trial/contracted research: AstraZeneca, Clovis Oncology, GSK, MSD, Seagen; Financial Interests, Institutional, Funding, Clinical trials/contracted research: Genmab, Immunogen, Incyte, Novartis, Roche; Non-Financial Interests, Principal Investigator, PI of several trials, no compensation received: GSK; Non-Financial Interests, Principal Investigator, PI of several trials. No personal compensation received: AstraZeneca, Genmab; Non-Financial Interests, Principal Investigator, PI in several trials. No personal compensation received: MSD; Non-Financial Interests, Principal Investigator, PI of clinical trial. No personal compensation received: immunogen, clovis, Incyte; Non-Financial Interests, Principal Investigator, PI of clinical trial. No personal compensation receive: Roche; Non-Financial Interests, Member, Board of Directors: GCIG. D. Cibula: Financial Interests, Personal, Advisory Board: Roche, Sotio, Novocure, MSD, GSK, Akesobio, Seagen; Financial Interests, Personal, Invited Speaker: AstraZeneca. A. Oaknin: Financial Interests, Personal, Advisory Board: AstraZeneca, Clovis Oncology, Deciphera Pharmaceuticals, Genmab, GSK, Immunogen, Mersana Therapeutics, PharmaMar, Roche, Tesaro, Merck Sharps & Dohme de España, SA, Agenus, Sutro, Corcept Therapeutics, EMD Serono, Novocure, prIME Oncology, Sattucklabs, Itheos, Eisai, F. Hoffmann-La Roche,; Financial Interests, Personal, Other, Travel and accomodation: AstraZeneca, PharmaMar, Roche; Financial Interests, Institutional, Funding: Abbvie Deutschland, Advaxis Inc., Aeterna Zentaris, Amgen, Aprea Therapeutics AB, Clovis Oncology Inc, EISAI limited LTD, F. Hoffmann –La Roche LTD, Regeneron Pharmaceuticals, Immunogen Inc, Merck, Sharp & Dohme de España SA, Millennium Pharmaceuticals Inc, PharmaMar SA, Tesaro Inc., Bristol Myers Squibb; Non-Financial Interests, Leadership Role, Executive Board member as a Co-Chair: GEICO; Non-Financial Interests, Leadership Role, Phase II Committee and Cervix Cancer Committee Representative on behalf of GEICO: GCIG; Non-Financial Interests, Officer, Chair of Gynaecological Track ESMO 2019. Scientific Track Member Gynaecological Cancers ESMO 2018, ESMO 2020, ESMO 2022. Member of Gynaecological Cancers Faculty and Subject Editor Gyn ESMO Guidelines: ESMO; Non-Financial Interests, Member: ESMO, ASCO, GCIG, SEOM, GOG. B. Maćkowiak-Matejczyk: Financial Interests, Personal, Invited Speaker, honoraria: AstraZeneca, GlaxoSmithKline, Roche; Financial Interests, Personal, Advisory Board: Seagen , GlaxoSmithKline; Financial Interests, Personal and Institutional, Funding: Clovis Oncology, Inc., AstraZeneca AB, AstraZeneca Pharma Poland sp zoo, MERSANA Therapeutics, MSD Polska Sp zoo, Parexel International Limited, Quiniles Eastern Holdings, Regeneron Pharmaceuticals, Roche Polska sp zoo, Seagen, Tesaro, Tesaro Bio Netherlands BV. D. Thomas: Financial Interests, Personal, Full or part-time Employment: Clovis Oncology, Inc.; Financial Interests, Personal, Stocks/Shares: Clovis Oncology, Inc. K.K. LIN: Financial Interests, Personal, Full or part-time Employment: Clovis Oncology, Inc.; Financial Interests, Personal, Stocks/Shares: Clovis Oncology, Inc. K. McLachlan: Financial Interests, Personal, Full or part-time Employment: Clovis Oncology, Inc.; Financial Interests, Personal, Stocks/Shares: Clovis Oncology, Inc. S. Goble: Financial Interests, Personal, Full or part-time Employment: Clovis Oncology, Inc.; Financial Interests, Personal, Stocks/Shares: Clovis Oncology, Inc. R. Kristeleit: Financial Interests, Personal, Advisory Board: GSK, Eisai, Basilea Pharmaceutica, iTEOS, Clovis Oncology, Shattuck Labs, AstraZeneca, Regeneron; Financial Interests, Personal, Invited Speaker: GSK, Zydus Cadila, Clovis Oncology, AstraZeneca, GSK; Financial Interests, Personal, Expert Testimony: Amgen; Financial Interests, Personal, Other, Membert of Oncology and Haematology Expert Advisory Group: Commission on Human Medicines; Financial Interests, Institutional, Invited Speaker: GSK, Clovis Oncology, Clovis Oncology, Eisai, InCyte, AstraZeneca, MSD, Roche, BerGenBio, Allarity, IoVance, Artios, Regeneron; Financial Interests, Institutional, Research Grant: MSD. All other authors have declared no conflicts of interest.

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