732P - Durvalumab + carboplatin/paclitaxel (CP) followed by durvalumab ± olaparib as a first-line treatment for endometrial cancer (EC): Progression-free survival (PFS) by clinical factors in DUO-E

Background

DUO-E met its primary endpoints, demonstrating a statistically significant PFS benefit with CP + durvalumab followed by durvalumab ± olaparib v CP in the intent-to-treat (ITT) population. We present further exploratory PFS analyses of key clinical factors in the ITT and mismatch repair populations (deficient [dMMR] and proficient [pMMR]).

Methods

Patients (pts) with newly diagnosed stage III/IV or recurrent EC were randomized 1:1:1 to CP (CP + durvalumab placebo [pbo] followed by durvalumab pbo + olaparib pbo), CP+D (CP + durvalumab followed by durvalumab + olaparib pbo), or CP+D+O (CP + durvalumab followed by durvalumab + olaparib). Post hoc exploratory PFS subgroup analyses by key clinical factors: age (<65 v ≥65 years); BMI (<25 v ≥25); ECOG performance status (PS; 0 v 1); and prior chemotherapy, surgery and radiotherapy (yes v no) in the ITT and mismatch repair populations are reported.

Results

At primary data cutoff (12 Apr 2023), PFS subgroup analyses by age, BMI, ECOG PS and prior treatment generally showed benefit for CP+D±O v CP in the ITT population (Table). PFS subgroup analyses showed consistent PFS benefit for CP+D v CP in dMMR pts (HRs <1.00 in all subgroups). In pMMR pts, CP+D generally showed benefit v CP, with addition of olaparib consistently enhancing PFS (HRs <1.00 for CP+D+O v CP in all subgroups).Table: 732P

∗Data missing for 2 pts in both CP and CP+D, 1 pt in CP+D+O.

†Overweight/obesity.
e, events;
n, patients; $
N, no;
Y, yes

Conclusions

The DUO-E ITT population derived PFS benefit with CP+D±O v CP across a range of key clinical factors explored in these analyses. In dMMR pts, a consistent PFS benefit was observed across key clinical factors for CP+D v CP. pMMR pts derived benefit from CP+D v CP across a range of key clinical factors, with addition of olaparib consistently enhancing PFS within each subgroup category. These DUO-E subgroup analyses support prior PFS analyses of the ITT and dMMR populations (benefit for CP+D v CP), with enhanced benefit in pMMR pts with the addition of olaparib.

Clinical trial identification

NCT04269200.

Editorial acknowledgement

Medical writing assistance was provided by Tobias M. Hedison, PhD, at Cence, funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

S.V. Blank: Financial Interests, Personal, Other, Division member: American Board of Obstetrics and Gynecology; Non-Financial Interests, Personal, Member of Board of Directors: SHARE, The Chemotherapy Foundation, HPV Alliance, NOCC; Financial Interests, Institutional, Research Funding, Contracted research with institution: AstraZeneca, Acrivon, Merck, Zentalis, GSK, Roche; Financial Interests, Institutional, Research Funding: Any Mountain. D.L. Richardson: Financial Interests, Personal, Advisory Board: AstraZeneca, GSK, ImmunoGen, Daiichi Sankyo, Mersana, Eisai, ProfoundBio; Financial Interests, Institutional, Research Funding: GSK; Financial Interests, Personal, Steering Committee Member: Karyopharm; Non-Financial Interests, Personal, Member of Board of Directors: SGO, National Ovarian Cancer Coalition. B.M. Slomovitz: Financial Interests, Personal, Advisory Board: AstraZeneca, Eisai, GSK, Genentech, Merck, ImmunoGen, Novocure, Aadi, Seagen, Incyte; Non-Financial Interests, Member of Board of Directors: GOG Foundation. C. Papadimitriou: Financial Interests, Personal, Other, Honoraria: Novartis, AstraZeneca, MSD Oncology, Servier, WinMedica; Financial Interests, Personal, Advisory Role: Amgen, Astellas, BioPharma, Roche Hellas, AstraZeneca; Financial Interests, Personal and Institutional, Research Funding: Roche Hellas, WinMedica, Servier. K. Grisan: Financial Interests, Personal, Advisory Role: GSK; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Other, Travel, accommodation, expenses: AstraZeneca, Pfizer, Genekor, GSK, MSD. M. Kowgier: Financial Interests, Personal, Other, Employment: AstraZeneca; Financial Interests, Personal, Stocks or ownership: AstraZeneca. P.M.D. Del Rosario: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. E. Van Nieuwenhuysen: Financial Interests, Institutional, Advisory Board: Regeneron, Oncoinvent; Financial Interests, Institutional, Local PI: Regeneron, Oncoinvent, Roche, Seagen, Merck, Novartis; Financial Interests, Institutional, Steering Committee Member: AstraZeneca; Financial Interests, Institutional, Coordinating PI: AstraZeneca. S. Westin: Financial Interests, Personal, Advisory Role: Roche, AstraZeneca, Genentech, Medscape, Clovis Oncology, Gerson Lehrman Group, Vaniam Group, Merck, BioAscent, OncLive, Targeted Oncology, Curio Science, GSK, Eisai, Zentalis, EQRX, Lilly, Vincerx Pharma, Mereo BioPharma, ImmunoGen, Mersana, NGM Biopharmaceuticals, Caris Life Sciences, Nuvectis Pharma, Seagen, Immunocore, ZielBio, Verastem, Gilead Sciences, pharma&; Financial Interests, Institutional, Research Funding: AstraZeneca, Novartis, Bayer, Clovis Oncology, Roche/Genentech, GOG Foundation, Mereo BioPharma, Bio-Path Holdings, Inc, GSK, Zentalis, Avenge Bio, Jazz Pharmaceuticals, Nuvectis Pharma. All other authors have declared no conflicts of interest.