43O - Durvalumab (D) + carboplatin/paclitaxel (CP) + bevacizumab (B) followed by D, B + olaparib (O) maintenance (mtx) for newly diagnosed advanced ovarian cancer (AOC) without a tumour BRCA1/BRCA2 mutation (non-tBRCAm): Updated results from DUO-O

Background

DUO-O, a phase III, placebo-controlled study, showed statistically significant and clinically meaningful PFS benefit with D + CP + B followed by D + B + O mtx vs CP + B followed by B in non-tBRCAm HRD+ and non-tBRCAm ITT populations (primary endpoint; Harter JCO 2023;41:17; LBA5506). We report updated data.

Methods

Patients (pts) had newly diagnosed high-grade epithelial AOC and primary, or planned interval, debulking surgery. After 1 cycle of CP ± B, pts with non-tBRCAm AOC were randomized 1:1:1, stratified by timing and outcome of cytoreductive surgery (no macroscopic residual disease after upfront primary surgery and all others), and geographic region (North America, Europe, and other regions), to Arm 1 (control): CP + B followed by B; Arm 2: D + CP + B followed by D + B; or Arm 3: D + CP + B followed by D + B + O mtx. We present final descriptive PFS and subgroup analyses (Arm 3 vs 1); secondary endpoints of PFS (Arm 2 vs 1; non-tBRCAm ITT) and interim OS (both formally tested per the predefined multiple testing procedure); and PFS2.

Results

At DCO2 (18 Sep 2023), PFS benefit for Arm 3 vs 1 was sustained in both the non-tBRCAm HRD+ and non-tBRCAm ITT populations (Table), and was consistent across preplanned subgroups, including for the stratification factors. The interim OS analysis for Arm 3 vs 1 (non-tBRCAm ITT) was not statistically significant. A favourable OS trend was shown for Arm 3 vs 1 in the non-tBRCAm HRD+ population. In both populations, PFS2 was improved for Arm 3 vs 1 and Arm 2 vs 1 (Table). DCO2 safety findings were similar to DCO1.Table: 43O

*Myriad MyChoice® CDx assay, genomic instability score ≥42.^†vs Arm 1. Estimated from a stratified Cox model (stratified by timing and outcome of cytoreductive surgery [HRD+: PFS, OS, PFS2] or by timing and outcome of cytoreductive surgery and geographic region [ITT: PFS]) or an unstratified Cox model (ITT: OS, PFS2).

Conclusions

D + CP + B followed by D + B + O mtx continued to improve PFS vs control, including by subgroup; in the non-tBRCAm HRD+ population, median PFS was 45.1 mo, the longest seen for these pts in the first-line setting to date, with an associated favourable OS trend. PFS2 was improved in both the non-tBRCAm HRD+ and non-tBRCAm ITT populations.

Clinical trial identification

NCT03737643.

Editorial acknowledgment

Medical writing assistance was provided by Abbie Newman BSc, Cence, funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

F. Trillsch: Financial Interests, Personal, Advisory Board: AstraZeneca, ImmunoGen, GSK, Eisai, MSD; Financial Interests, Personal, Invited Speaker: AstraZeneca, MSD; Financial Interests, Personal, Other, Honoraria: AstraZeneca, GSK, MSD; Financial Interests, Personal, Other, Travel expenses: AstraZeneca, ImmunoGen, GSK; Financial Interests, Institutional, Funding, Research funding: AstraZeneca, SAGA diagnostics. A. Okamoto: Financial Interests, Personal, Invited Speaker, Lecture fee: AstraZeneca K.K. V. Salutari: Financial Interests, Personal and Institutional, Advisory Board: MSD, AstraZeneca; Financial Interests, Personal and Institutional, Invited Speaker: MSD, AstraZeneca; Financial Interests, Personal, Advisory Board: GSK, Eisai; Financial Interests, Personal, Invited Speaker: GSK, Eisai. J. Frenel: Financial Interests, Personal and Institutional, Advisory Board: AstraZeneca, Daiichi Sankyo, GSK, Gilead, Novartis, Lilly, Pfizer, MSD; Financial Interests, Personal and Institutional, Invited Speaker: AstraZeneca, Daiichi Sankyo, GSK, Gilead, Novartis, Lilly, Pfizer, MSD. N. Colombo: Financial Interests, Personal, Advisory Board: AstraZeneca, GSK, Clovis Oncology, Eisai, Immunogen, Mersana, MSD/Merck, Oncxerna, Pfizer, Pieris, Roche, Novocure; Financial Interests, Personal, Invited Speaker: AstraZeneca, GSK, Clovis Oncology, EISAI, MSD/Merck; Financial Interests, Personal, Other: Nuvation Bio. A.M. Chudecka-Glaz: Financial Interests, Personal, Other, Honoraria: AstraZeneca, GSK Company, Novocure Company, Aravive INC; Financial Interests, Personal, Advisory Role: GSK Company. S. Lheureux: Financial Interests, Personal, Advisory Role: AstraZeneca, Merck, GSK, Shattuck Labs, Novartis, Roche/Genentech; Financial Interests, Personal, Other, Honoraria: AstraZeneca, Merck, GSK, Shattuck Labs, Roche/Genentech; Financial Interests, Institutional, Funding, Research funding: Tesaro, AstraZeneca, Roche/Genentech, Regeneron, Merck, GSK, Repare Therapeutics. T. Engler: Financial Interests, Personal and Institutional, Advisory Board: AstraZeneca, GSK, Gilead, Novartis, Eli Lilly, Pfizer, MSD, Stemline, Roche; Financial Interests, Personal and Institutional, Invited Speaker: AstraZeneca, GSK, Gilead, Novartis, Eli Lilly, Pfizer, MSD, Roche; Financial Interests, Personal and Institutional, Funding, Research funding: AstraZeneca, Daiichi Sankyo, GSK, Gilead, Novartis, Eli Lilly, Pfizer, MSD, Stemline, Roche; Financial Interests, Personal and Institutional, Other, Congress travel expenses: Daiichi Sankyo, GSK, Gilead, Eli Lilly; Financial Interests, Personal and Institutional, Other, Honoraria publication: GSK; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Other, Congress travel expenses: Pierre Fabre; Financial Interests, Institutional, Funding, Research funding: Exscientia, Tesaro. R.M. Wenham: Financial Interests, Personal and Institutional, Funding, Research funding: GSK/Tesaro, Eisai, AstraZeneca, Merck, Genentech, Seagen, Sonnett Biotherapeutics, Tapimmune, Mersana, Regeneron, OnTarget Labs, Ovation Diagnostics; Financial Interests, Personal and Institutional, Other, Consulting fees: GSK/Tesaro, Eisai, AstraZeneca, Merck, Genentech, Seagen, Sonnett Biotherapeutics, Tapimmune, Mersana, Regeneron, OnTarget Labs, Ovation Diagnostics; Financial Interests, Personal and Institutional, Invited Speaker: GSK/Tesaro; Financial Interests, Personal, Invited Speaker: Curioscience, OncLive; Financial Interests, Personal, Other, Consulting fees: Shattuck Labs, Clovis, Legend Biotech; Financial Interests, Personal, Funding, Research funding: Clovis; Financial Interests, Institutional, Funding, Research funding: Anixa Biosciences. A. Correa: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. P. Harter: Financial Interests, Personal, Advisory Board, Value includes honoraria for lectures: AstraZeneca; Financial Interests, Personal, Advisory Board, includes honoraria for lectures: GSK, Roche, MSD; Financial Interests, Personal, Invited Speaker: Amgen, Stryker, Zailab, Eisai, Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Clovis, Immunogen, Novartis, Mersana, Miltenyi; Financial Interests, Personal, Other, IDMC member: Sotio; Financial Interests, Personal, Expert Testimony: Exscientia; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Roche, GSK, Genmab, Immunogen; Financial Interests, Institutional, Funding: Seagen, Clovis; Financial Interests, Institutional, Other, Co-investigator: Novartis; Non-Financial Interests, Personal, Principal Investigator: AstraZeneca; Other, Personal, Other, Travel support for conference: AstraZeneca. C. Aghajanian: Financial Interests, Institutional, Funding, Clinical trial funding to institution (MSK): AbbVie, Artios Pharma, AstraZeneca, Clovis, Genentech/Roche; Non-Financial Interests, Personal and Institutional, Advisory Board, no consulting fee: Blueprint Medicine; Financial Interests, Personal and Institutional, Advisory Board: Merck, AstraZeneca; Financial Interests, Personal and Institutional, Other, AZ eVOLVE DMC 4/26/23-ongoing: AstraZeneca; Non-Financial Interests, Personal, Member of Board of Directors, Unpaid: GOGFoundation, NRG Oncology . All other authors have declared no conflicts of interest.