517O - Overall survival (OS) at 7-year (y) follow-up (f/u) in patients (pts) with newly diagnosed advanced ovarian cancer (OC) and a BRCA mutation (BRCAm) who received maintenance olaparib in the SOLO1/GOG-3004 trial

Background

In the Phase III SOLO1/GOG-3004 trial (NCT01844986), maintenance olaparib provided sustained benefit beyond the end of treatment in pts with newly diagnosed advanced OC and a BRCAm. At 5-y f/u, median progression-free survival was 56.0 months [m] with olaparib vs 13.8m with placebo (pbo) (HR 0.33; 95% CI 0.25–0.43); 48% vs 21% of pts, respectively, were progression-free (KM estimates) (Banerjee et al. Lancet Oncol 2021). Given that most OC deaths occur 5‒10y after diagnosis, we report OS in SOLO1 at 7-y f/u, a clinically relevant timepoint.

Methods

Pts who were in response to first-line platinum-based chemotherapy received maintenance olaparib tablets 300 mg bid or pbo for up to 2y or until progression. A descriptive analysis of OS, a secondary endpoint, was performed 7y after the last pt was randomized; prespecified final analysis of OS is planned at 60% data maturity.

Results

260 pts were randomized to olaparib and 131 to pbo (median treatment duration 24.6 vs 13.9m, respectively). At OS data maturity of 38.1% (data cut-off 7 Mar 2022), median OS was not reached in olaparib pts vs 75.2m in pbo pts, with an OS HR of 0.55 (95% CI 0.40–0.76; unadjusted for crossover; 44.3% of pbo pts received a PARP inhibitor in a subsequent line of therapy) (Table). At 7y, 45.3% of olaparib pts vs 20.6% of pbo pts were alive and had still not received a first subsequent treatment (KM estimates). The incidence of MDS/AML remained low and new primary malignancies remained balanced between arms (Table). Table: 517O

*P<0.0001 required for statistical significance; ^†KM estimates; ^‡1 pt randomized to pbo did not receive treatment. AE, adverse event; AML, acute myeloid leukaemia; CI, confidence interval; HR, hazard ratio; KM, Kaplan–Meier; MDS, myelodysplastic syndrome; NR, not reached.

Conclusions

2y of maintenance olaparib provided a clinically meaningful improvement in OS over pbo in pts with newly diagnosed advanced OC and a BRCAm. At 7y, 67.0% of olaparib pts vs 46.5% of pbo pts were alive; no new safety signals were detected. These data provide the longest f/u for any PARP inhibitor in this setting and support use of maintenance olaparib to achieve long-term remission and enhance the potential for cure.

Clinical trial identification

NCT01844986.

Editorial acknowledgement

Medical writing assistance was provided by Gillian Keating, MBChB, of Cence, funded by AstraZeneca and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Legal entity responsible for the study

AstraZeneca.

Funding

This study was funded by AstraZeneca and is part of an alliance between AstraZeneca and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Disclosure

S. Banerjee: Financial Interests, Institutional, Research Grant: AstraZeneca, GSK, Tesaro; Financial Interests, Personal, Funding, Personal and consulting fees: AstraZeneca, GSK, Amgen, Pfizer; Financial Interests, Personal, Funding, Consulting fees: Epsilogen, Genmab, ImmunoGen, Mersana, MSD, Merck Serono, Oncxerna, Roche; Non-Financial Interests, Personal, Advisory Board, Unpaid: Epsilogen; Financial Interests, Personal, Funding, Personal fees: Tesaro, Clovis Oncology, Takeda; Financial Interests, Personal, Funding, Travel: Nucana; Non-Financial Interests, Personal, Member, Director of Membership: unpaid: European Society of Medical Oncology . N. Colombo: Financial Interests, Institutional, Research Grant: AstraZeneca, PharmaMar, Roche; Financial Interests, Personal, Funding, Personal and consulting fees: AstraZeneca, Clovis Oncology, Eisai, GSK, Merck Sharp & Dohme, Tesaro; Financial Interests, Personal, Funding, Consulting fees: Biocad, Roche, PharmaMar, ImmunoGen, Mersana, Oncxerna, Pfizer; Financial Interests, Personal, Funding, Personal fees: Novartis. G. Scambia: Financial Interests, Institutional, Research Grant: MSD Italia S.r.l.; Financial Interests, Personal, Funding, Consulting fees: Johnson & Johnson, Tesaro; Financial Interests, Personal, Speaker’s Bureau: Clovis Oncology. A. Oaknin: Financial Interests, Institutional, Research Grant: AbbVie Deutschland, Abililty Pharmaceuticals, Advaxis Inc, Aeterna Zentaris, Amgen SA, Aprea Therapeutics AB, Bristol Myers Squibb, Clovis Oncology Inc, Eisai Ltd, F, F. Hoffmann-La Roche Ltd, ImmunoGen Inc, Merck, Sharp & Dohme de España SA, Millennium Pharmaceuticals Inc., PharmaMar SA, Regeneron Pharmaceuticals, Tesaro; Financial Interests, Personal, Funding, Personal fees: Clovis Oncology Inc, Deciphera Pharmarceutia, Genmab, GSK, ImmunoGen, Mersana Therapeutic, Sutro; Financial Interests, Personal, Funding, Personal and travel fees: PharmaMar, AstraZeneca, Roche. M.L. Friedlander: Financial Interests, Personal, Advisory Board: AstraZeneca, Novartis, GSK, Lilly, Takeda; Financial Interests, Institutional, Research Grant: AstraZeneca, Novartis, BeiGene; Financial Interests, Personal, Funding, Travel fees: AstraZeneca; Financial Interests, Personal, Funding, Personal lecture fees: GSK, Act Genomics; Financial Interests, Personal, Member: MSD, AGITG IDMSC; Financial Interests, Personal, Funding, Consulting fees: AbbVie. A. Floquet: Financial Interests, Personal, Funding, Travel fees: AstraZeneca. A. Leary: Financial Interests, Institutional, Research Grant: AstraZeneca, Sanofi; Financial Interests, Personal, Advisory Board: AstraZeneca, Ability Pharma, Biocad, Clovis Oncology, GSK , Medscape, Merck Serono, MSD, Touch Congress, Zentalis, ARIEL4 , TROPHIMMUNE; Financial Interests, Personal, Funding, Travel fees: AstraZeneca, Clovis Oncology, GSK, Roche; Financial Interests, Personal, Funding, Consulting fees: Seattle Genetics. G.S. Sonke: Financial Interests, Institutional, Research Grant: AstraZeneca, Novartis, Roche; Financial Interests, Institutional, Funding, Consulting fees: Biovica, Seagen. C. Gourley: Financial Interests, Institutional, Research Grant: AstraZeneca, BergenBio, Clovis Oncology, GSK, Medannexin, MSD, Novartis, Nucana, Aprea, Tesaro; Financial Interests, Personal, Funding, Consulting fees: AstraZeneca, GSK, MSD, Tesaro; Financial Interests, Personal, Funding, Lecture fees: AstraZeneca, Clovis Oncology, GSK, MSD, Nucana, Tesaro, Chugai, Roche, Takeda, Cor2Ed; Financial Interests, Personal, Advisory Board: AstraZeneca, GSK, MSD, Nucana, Tesaro, Chugai, Roche; Financial Interests, Personal, Member: Scottish Medicines Consortium. A.M. Oza: Financial Interests, Institutional, Research Grant: AstraZeneca. A.J. Gonzalez Martin: Financial Interests, Institutional, Research Grant: GSK, Roche; Financial Interests, Personal, Funding, Consulting fees: GSK, Roche, Alkermes, Amgen, AstraZeneca, Clovis Oncology, Genmab, Immunogen, Mersana, MSD, Oncoinvent, PharmaMar, Sotio, Takeda; Financial Interests, Personal, Funding, Personal and travel fees: GSK, Roche, AstraZeneca, MSD, PharmaMar; Financial Interests, Personal, Funding, Personal fees: Clovis Oncology; Financial Interests, Personal, Member of the Board of Directors: GEICO, ENGOT. C. Aghajanian: Financial Interests, Personal, Advisory Board: AbbVie, AstraZeneca/Merck, Eisai/Merck, Mersana Therapeutics, Repare Therapeutics, Roche/Genentech, Blueprint Medicine; Financial Interests, Institutional, Research Grant: AbbVie, AstraZeneca, Clovis Oncology, Genentech; Financial Interests, Personal, Member of the Board of Directors: GOGFoundation, NRG Oncology. C. Mathews: Financial Interests, Institutional, Research Grant: Syros, Deciphera, Astellas Pharma, GSK/Tesaro, Seattle Genetics, EMD Serono, Merck, Regeneron, Moderna, AstraZeneca, Laekna. J. McNamara: Financial Interests, Institutional, Full or part-time Employment, Stocks: AstraZeneca. E. Lowe: Financial Interests, Institutional, Full or part-time Employment, Stocks: AstraZeneca. K.N. Moore: Financial Interests, Personal, Research Grant, Contracts for ovarian cancer investigator-initiated trials: Genentech/Roche, Lilly Pharmaceuticals, PTC Therapeutics; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Funding, Consulting fees: IMab; Financial Interests, Institutional, Funding, Payment for educational content: Onc Live, Physician Education Resource (PER), PRIME Oncology, Research to Practice; Financial Interests, Institutional, Advisory Board: Alkemeres, Aravive, Blueprint Pharmaceuticals, Eisai, Genentech/Roche, ImmunoGen, Mersana, Mereo, VBL Therapeutics; Financial Interests, Personal, Member, Participation on a data safety monitoring board: Incyte; Financial Interests, Institutional, Member, Associate Director: GOG partners; Financial Interests, Institutional, Member, Committee chair: NRG Ovarian Cancer. All other authors have declared no conflicts of interest.