LBA29 - Final overall survival (OS) in patients (pts) with newly diagnosed advanced ovarian cancer (aOC) treated with niraparib (nir) first-line (1L) maintenance: Results from PRIMA/ENGOT-OV26/GOG-3012

Background

The phase 3 PRIMA trial met its primary endpoint, demonstrating that nir 1L maintenance significantly extended progression-free survival (PFS) in pts with aOC that responded to 1L platinum-based chemotherapy (PBCT) in the homologous recombination-deficient (HRd) and overall populations (González-Martín A, et al. N Engl J Med. 2019;381(25);2391–2402). Here, we report final planned OS and updated ad hoc PFS results.

Methods

In PRIMA, 733 pts were randomized 2:1 to maintenance nir or placebo (PBO), stratified by response to 1L PBCT, receipt of neoadjuvant PBCT, and tumor homologous recombination deficiency (HRD) status. OS testing occurred after 60% maturity was reached in the overall population (pop), and was hierarchical (overall first, then HRd). Other secondary efficacy outcomes and long-term safety were assessed; an updated, ad hoc analysis of investigator-assessed PFS was also conducted (data cutoff, 08Apr2024).

Results

Median follow-up was 73.9 mo; OS, time to first subsequent therapy, and PFS2 are shown in the table. In the overall pop, the OS hazard ratio (HR) was 1.01 (95% CI, 0.84–1.23) for nir vs PBO. OS HR was 0.95 (95% CI, 0.70–1.29) in the HRd pop and was 0.93 (95% CI 0.69–1.26) in the homologous recombination-proficient pop. In the overall pop, 11.7% of nir and 37.8% of PBO pts received subsequent PARP inhibitor (PARPi) therapy (HRd pop: nir, 15.8%; PBO, 48.4%). 5 y PFS in the overall pop was 22% for nir vs 12% for PBO (HRd pop: 35% vs 16%). MDS/AML incidence was

Conclusions

In pts with newly diagnosed aOC at high risk for recurrence, no difference in OS was observed between treatment arms. There was a higher rate of subsequent PARPi use in the PBO arm. In the HRd pop, pts alive at 5 y were twice as likely to be progression free with nir treatment than PBO. Long-term safety data remained consistent with the known safety profile of nir.

Clinical trial identification

NCT02655016.

Editorial acknowledgement

Writing and editorial support, funded by GSK (Waltham, MA, USA) and coordinated by Hasan H. Jamal, MSc, of GSK, was provided by Betsy C. Taylor, PhD, CMPP, and Mary C. Wiggin of Ashfield MedComms, an Inizio company.

Legal entity responsible for the study

This study was designed and sponsored by Tesaro, Inc, a fully owned subsidiary of GSK, in collaboration with the authors and academic groups under the European Network of Gynaecological Oncological Trial groups (ENGOT) and the Gynecologic Oncology Group (GOG) Foundation, according to the ENGOT model C.

Funding

This study (NCT02655016) was sponsored by Tesaro, Inc, a fully owned subsidiary of GSK (Waltham, MA, USA).

Disclosure

A. González-Martín: Financial Interests, Personal, Advisory Role: Alkermes, Amgen, AstraZeneca, Clovis, Genmab, GSK, Hedera Dx, Immunogen, Illumina, Karyopharm, Mersana, MSD, Novartis, Novocure, Oncoinvent, PharmaMar, Regeneron, Roche, Seagen, Sotio, Sutro, Takeda, Tubulis. B. Pothuri: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, BioNTech, Celsion, Daiichi Sankyo, Duality Bio, Eisai, GOG Foundation, ImmunoGen, Imvax Inc, Incyte Corporation, InxMed, Lily, Onconova Therapeutics, OnCusp, R Pharm, Regeneron, Seagen, Signatera, Sutro Biopharma, Tesaro, GSK; Financial Interests, Personal, Other, payment or honoraria for lectures presentations, speakers’ bureaus, manuscript writing, or educational events: Albert Einstein-Montefiore, Bioascend, Colorado University, Curio, Lankenau Hospital, OncLive, Peer View, PERS, Vanium, Yale University; Financial Interests, Personal, Other, grants or contracts: Acrivon, Agenus, Alkermes, AstraZeneca, Celgene, Celsion/Immunon, Clovis Oncology, Duality Bio, Eisai, Imab, ImmunoGen, Incyte, InxMed, Karyopharm Therapeutics, LOXO/Lily, Merck, Mersana, Novocure, NRG Oncology, Onconova, Roche/Genentech, Seagen, Sutro Biopharma, Takeda, Tesaro/GSK, Toray, VBL Therapeutics, Xencor; Financial Interests, Personal, Other, support for attending meetings and/or travel: GOG Partners; Financial Interests, Personal, Advisory Board, participation on a data safety monitoring board or advisory board: AstraZeneca, BioNTech, Celsion/Immunon, GOG Foundation, Imab, Imvax, InxMed, Merck, Mersana, Nuvation, Sutro, Tesaro/GSK, Toray; Financial Interests, Personal, Leadership Role, participation on a data safety monitoring board or advisory board: GOG Foundation; Financial Interests, Personal, Leadership Role: GOG Partners, NYOB Society (Vice President), SGO Board of Directors. M.P. Barretina Ginesta: Financial Interests, Personal, Advisory Board, consulting or advisory role fees: AstraZeneca, Clovis Oncology, GSK, MSD, PharmaMar, Roche; Financial Interests, Personal, Other, travel support: AstraZeneca, GSK, MSD, PharmaMar, Roche. W.S. Graybill: Financial Interests, Personal, Speaker, Consultant, Advisor: GSK. I.B. Vergote: Financial Interests, Personal, Speaker, Consultant, Advisor: Akesobio, Bristol Myers Squibb, Deciphera Pharmaceuticals, Eisai, Elevar Therapeutics, F. Hoffmann-La Roche, Genmab, GSK, ITM, Jazzpharma, Karyopharm, MSD, Novocure, Oncoinvent, Sanofi, Seagen, Sotio, Regeneron, Zentalis; Financial Interests, Personal, Other, payments for data monitoring committees: Agenus, AstraZeneca, Corcept, Daiichi Sankyo, Exelixis, F. Hoffmann-La Roche, ImmunoGen, Kronos Bio, Mersana, Novartis, OncXerna, Verastem Oncology. C. McCormick: Financial Interests, Personal, Advisory Board: Clovis, GSK, ImmunoGen, Merck. M.R. Mirza: Financial Interests, Personal, Advisory Board: Allarity Therapeutics, AstraZeneca, Biocad, BioNTech, Boehringer Ingelheim, Clovis, Daiichi Sankyo, Eisai, Genmab, GSK, ImmunoGen, Incyte, Karyopharm, Merck/MSD, Mersana, Novartis, Regeneron, Roche, Seagen, Takeda, Tesaro, Zailab; Financial Interests, Personal, Member of Board of Directors, membership on the board of directors or stockholder/shareholder: Karyopharm Therapeutics, Sera Prognostics; Financial Interests, Institutional, Research Grant: Allarity, Apexigen, AstraZeneca, Boehringer Ingelheim, Clovis, GSK, Novartis, Tesaro, Ultimovacs; Financial Interests, Personal, Trial Chair: AstraZeneca, Boehringer Ingelheim, Deciphera, Daiichi Sankyo, GSK, Merck, Mersana, NuvationBio, Tesaro. R.G. Moore: Financial Interests, Personal, Speaker, Consultant, Advisor: Fujirebio Diagnostics Inc.. D. Lorusso: Financial Interests, Personal, Other, grants or contracts: Alkermes, AstraZeneca, Clovis Oncology, Corcept, Genmab, GSK, ImmunoGen, Incyte, MSD, Novartis, Pharma&, PharmaMar, Roche, Seagen; Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, Clovis Oncology, Corcept, Daiichi Sankyo, Genmab, GSK, ImmunoGen, MSD, Novartis, Novocure, Oncoinvest, Seagen, Sutro; Financial Interests, Personal, Other, honoraria: AstraZeneca, Corcept, Genmab, GSK, ImmunoGen, MSD, Seagen; Financial Interests, Personal, Other, support for attending meetings and/or travel: AstraZeneca, GSK, Menarini, MSD; Financial Interests, Personal, Advisory Board, participation on a data safety monitoring board or advisory board: AstraZeneca, Clovis Oncology, Corcept, Daiichi Sankyo, Genmab, GSK, ImmunoGen, MSD, Novocure, Oncoinvest, Seagen, Sutro; Financial Interests, Personal, Leadership Role, leadership or fiduciary roles: ENGOT, GCIG, MITO. R.E. O'Cearbhaill: Financial Interests, Personal, Other, support for the present manuscript: NCI/NIH P30 CA008748; Financial Interests, Institutional, Other, contracts or grants: AbbVie/StemCentrx, Acrivon, Alkermes/Mural Oncology, Arsenalbio, Atara Biotherapeutics, Bayer/Celgene/Juno, Genentech, Genmab/Seagen Therapeutics, Gynecologic Oncology Foundation, Kite Pharma, Ludwig Cancer Institute, Lyell Immunopharma, MarkerTherapeutics, Merck, OnCusp Therapeutics, Regeneron, Syndax Pharmaceuticals, TCR2 Therapeutics, Tesaro/GSK; Financial Interests, Personal, Other, payment or honoraria for lectures: Curio/OncLive/PER/MJH/Aptitude Health, GSK, Gynecologic Oncology Canada, Society for Immunotherapy of Cancer; Financial Interests, Personal, Other, support for attending meetings and/or travel: Gathering Around Center Ireland, GOG Foundation, Hitech Health, SGO; Financial Interests, Personal, Officer, participation on a data safety monitoring board or advisory board: 2seventybio; Financial Interests, Personal, Advisory Board, participation on a data safety monitoring board or advisory board: Acrivon, AstraZeneca, Bayer, Carina Biotech, GSK, ImmunoGen, Link Therapeutics, Loxo, Miltenyi, Mural Oncology, OnCusp Therapeutics, R-Pharm, Seattle Genetics/Seagen/Pfizer; Financial Interests, Personal, Leadership Role: NRG Oncology (Chair, Developmental Therapeutics Committee), SGO (Vice-Chair, Clinical Practice Committee). G. Freyer: Financial Interests, Personal, Other, honoraria: GSK. D.M. O'Malley: Financial Interests, Personal and Institutional, Other, grants and contracts: AbbVie, Agenus,Inc, Arcus Biosciences, Inc., AstraZeneca, Boston Biomedical, Clovis Oncology, Eisai, Exelixis, Genentech Inc, GSK, GOG Foundation, Hoffmann-La Roche Inc, ImmunoGen, Inc, Iovance Biotherapeutics, Leap Therapeutics, Inc, Merck & Co, Merck Sharp & Dohme, Mersana Therapeutics, Inc, Novartis, NovoCure, OncoC4, Inc, Regeneron Pharmaceuticals, Inc, Seagen, Sutro Biopharma, Verastem, Inc; Financial Interests, Personal, Other: AdaptImmune, Arquer Diagnostics, Atossa Therapeutics, Cardiff Oncology, Celcuity, Corcept Therapeutics, Duality Bio, Elevar, Genelux, Imvax, InterVenn, INXMED, Janssen, Jazz Pharmaceuticals, Laekna, Luzsana Biotechology, Myriad, Onconova, RepImmune, R Pharm, Roche Diagnostics, Sorrento, Tarveda Therapeutics, Toray, Trillium, Umoja, VBL Therapeutics, Vincerx Pharma, Xencor, Zentalis; Financial Interests, Institutional, Other, grants and contracts: Advaxis, Alkermes, Aravive, Inc, BeiGene USA, Inc, Bristol Myers Squibb, Deciphera Pharma, EMD Serono, Inc, Genmab, Incyte Corporation, Karyopharm, Ludwig Institute for Ca, NCI, NRG Oncology, OncoQuest Inc, Pfizer Inc, Precision Therapeutics, Inc, Prelude Therapeutics, RTOG, Rubius Therapeutics, SWOG. F. Heitz: Financial Interests, Personal, Other, honoraria: AstraZeneca, GSK, ImmunoGen, Merck; Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, GSK, ImmunoGen, NovoCure, PharmaMar, Roche, Tesaro, Zailabs. M.S. Shahin: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, GSK, ImmunoGen, Merck; Financial Interests, Personal, Other, honoraria: AstraZeneca, Eisai, GSK, ImmunoGen, Merck; Financial Interests, Personal, Member of Board of Directors: Unite for Her. W.H. Bradley: Financial Interests, Personal, Speaker, Consultant, Advisor: OncoC4; Financial Interests, Personal, Advisory Board, participation on a data safety monitoring board or advisory board: Imunon. N. Compton: Financial Interests, Personal, Full or part-time Employment, former employee: GSK; Financial Interests, Personal, Speaker, Consultant, Advisor: GSK. I. Malinowska: Financial Interests, Personal, Full or part-time Employment: GSK; Financial Interests, Personal, Stocks or ownership: GSK. A. Redondo: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, Boehringer Ingelheim, GSK, MSD, Pharma&; Financial Interests, Personal, Other, honoraria: AstraZeneca, GSK, MSD, Pharma&; Financial Interests, Personal, Other, support for attending meetings and/or travel: AstraZeneca, GSK, MSD. B.J. Monk: Financial Interests, Personal, Speaker, Consultant, Advisor: Acrivon, Adaptimune, Agenus, Akeso Bio, Amgen, Aravive, AstraZeneca, Bayer, Clovis, Easai, Elevar, EMD Merck, Genmab/Seagen, GOG Foundation, Gradalis, Heng Rui, ImmunoGen, Iovance, Karyopharm, Laekna, MacroGenics, Merck, Mersana, Myriad, Novartis, Novocure, OncoC4, Panavance, Pieris, Pfizer, Puma, Regeneron, Roche/Genentech, Sorrento, Teasro/GSK, US Oncology Research, VBL, Verastem, Zentalis; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Eisai, Myriad, Roche/Genentech, Tesaro/GSK. All other authors have declared no conflicts of interest.