LBA41 - Durvalumab (durva) plus carboplatin/paclitaxel (CP) followed by maintenance (mtx) durva ± olaparib (ola) as a first-line (1L) treatment for newly diagnosed advanced or recurrent endometrial cancer (EC): Results from the phase III DUO-E/GOG-3041/ENGOT-EN10 trial

Background

Combination of immunotherapy with CP led to improved progression-free survival (PFS) in patients (pts) with advanced EC. DUO-E (NCT04269200) evaluated addition of durva to standard 1L CP, followed by mtx durva ± ola, in pts with EC.

Methods

Pts with newly diagnosed FIGO Stage III/IV or recurrent EC and naïve to systemic treatment were randomised 1:1:1 to CP (CP + durva placebo [pbo] for 6 cycles followed by mtx durva pbo + ola pbo), CP + durva (CP + durva [1120 mg IV q3w] for 6 cycles followed by mtx durva [1500 mg IV q4w] + ola pbo), or CP + durva + ola (CP + durva for 6 cycles followed by mtx durva + ola [300 mg tablets bid]). Dual primary endpoints were PFS (investigator-assessed RECIST v1.1) in the intent-to-treat (ITT) population for CP + durva vs CP and CP + durva + ola vs CP; overall survival (OS) was a secondary endpoint. A multiple testing procedure with gatekeeping strategy was applied to PFS and OS. PFS by mismatch repair (MMR) status was a prespecified subgroup analysis.

Results

In the ITT population (N=718), CP + durva and CP + durva + ola showed statistically significant and clinically meaningful PFS benefit vs CP (Table). Interim OS data were immature (27.7%) yet with a trend towards benefit (CP + durva vs CP: HR [95% CI] 0.77 [0.56–1.07]; P=0.120; CP + durva + ola vs CP: 0.59 [0.42–0.83]; P=0.003). PFS subgroup analysis showed benefit for both arms vs CP in MMR-deficient (dMMR; n=143) and -proficient (pMMR) pts (n=545). In pMMR pts, mtx ola further enhanced PFS benefit (Table). Safety profiles of the treatment arms were generally consistent with individual components. Table: LBA41

*Vs CP; ^†In censored patients.

Conclusions

DUO-E met both primary endpoints, showing statistically significant and clinically meaningful PFS improvement with the addition of durva to CP followed by maintenance durva ± ola vs CP alone. Mtx ola further improved PFS in pts with pMMR disease.

Clinical trial identification

D9311C00001; NCT04269200.

Editorial acknowledgement

Medical writing assistance was provided by Simone Boldt, PhD, at Cence, funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca.

Funding

This study was funded by AstraZeneca.

Disclosure

S.N. Westin: Financial Interests, Institutional, Research Grant: AstraZeneca, AvengeBio, Bayer, Bio-Path, Clovis Oncology, GSK, Mereo, Novartis, Roche/Genentech, Zentalis; Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, Caris, Clovis Oncology, Eisai, EQRX, Gilead, GSK, ImmunoGen, Lilly, Merck, Mereo, Mersana, NGM Bio, Nuvectis, Roche/Genentech, SeaGen, Verastem, Vincerx, Zentalis, ZielBio. K.N. Moore: Financial Interests, Personal, Advisory Board: AstraZeneca, Aravive, Alkemeres, Blueprint Pharma, Eisai, Emd Serono, GSK/Tesaro, Genentech/Roche, Hengrui, Immunogen, IMab, Mereo, Myriad, Caris, Mersana, Novartis, Novocure, OncXerna, OncoNova, Tarveda, VBL Therapeutics, Clovis, Caris, Lilly, Nonvartis, Pannavance, Verastem, Zentalis, Merck; Financial Interests, Institutional, Advisory Board, advisory board work for gynecologic trial: Aadi; Financial Interests, Institutional, Advisory Board, work on clinical trial and planning for next trial: duality; Financial Interests, Personal, Full or part-time Employment: GOG Partners Associate Director; Financial Interests, Institutional, Full or part-time Employment: NRG Ovarian Cancer Chair; Financial Interests, Personal, Member of Board of Directors, not reimbursed: ASCO; Financial Interests, Institutional, Member of Board of Directors, not reimbursed: GOG Foundation; Financial Interests, Personal, Royalties: UP to Date; Financial Interests, Institutional, Coordinating PI, international CO-PI, local site PI: AstraZeneca; Financial Interests, Institutional, Coordinating PI: Immunogen, GSK/Tesaro, PTC Therapeutics, duality; Financial Interests, Institutional, Local PI: Lilly, Daiichi Sankyo, Regeneron, Artios, Bolt, verastem; Non-Financial Interests, Member of Board of Directors: GOG. J. Lee: Financial Interests, Personal, Invited Speaker: AstraZeneca, Takeda, MSD, Roche; Financial Interests, Personal, Advisory Board: Eisai, GI Innovation; Financial Interests, Institutional, Local PI: Alkermes, AstraZeneca, BergenBio, Cellid, Clovis Oncology, Eisai, GI Innovation, ImmunoGen, Janssen, Merck, Mersana, MSD, Novartis, OncoQuest, Roche, Seagen, Synthon; Financial Interests, Personal and Institutional, Local PI: BeiGene; Financial Interests, Personal, Steering Committee Member: AstraZeneca, OncoQuest, Seagen, ImmunoGen, MSD; Financial Interests, Institutional, Research Grant: ONO, Takeda. M. Sundborg: Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Speaker, Consultant, Advisor: GSK. J. de la Garza: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Merck, Seagen; Non-Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Other, DaVinci Robot proctor: Intuitive. T. Tillmanns: Financial Interests, Personal, Speaker, Consultant, Advisor: GSK, Eisai. F. Contreras Mejia: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Eli-Lilly, GSK, MSD, Novartis; Financial Interests, Personal, Advisory Board: BMS, Eli-Lilly, Janssen; Financial Interests, Personal, Expert Testimony: GSK, MSD. A.C. de Melo: Financial Interests, Institutional, Research Grant: Amgen, AstraZeneca, Bristol Myers Squibb, Clovis Oncology, GSK, Merck Sharp & Dohme, Novartis, Regeneron, and Roche; Financial Interests, Personal, Other, Honoraria for lectures: AstraZeneca, Bristol Myers Squibb, GSK, Merck Sharp & Dohme, Novartis, Roche, and Sanofi; Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myers Squibb, GSK, Merck Sharp & Dohme, Novartis, and Roche. D. Klasa-Mazurkiewicz: Financial Interests, Personal, Other, Honoraria for lectures: AstraZeneca, GSK and Roche. C.A. Papadimitriou: Financial Interests, Personal, Other, Honoraria: Novartis, AstraZeneca, Genesis, MSD Oncology, Servier, WinMedica; Financial Interests, Personal, Advisory Role: Amgen, Astellas, BioPharma, Roche Hellas, AstraZeneca; Financial Interests, Institutional, Research Funding: Roche Hellas, WinMedica, Servier. M. Gil Martín: Financial Interests, Personal, Invited Speaker: MSD, AstraZeneca, GSK; Financial Interests, Personal, Other, Registration and attending scientific meetings: MSD, Clovis, GSK.. B. Brasiuniene: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Expert Testimony: AstraZeneca; Financial Interests, Personal, Other, Reimbursement of travel expenses: AstraZeneca; Non-Financial Interests, Personal, Advisory Board, Member of NSGO and NSGO-CTU scientific committee member: NSGO. C. Donnelly: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. X. Liu: 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. All other authors have declared no conflicts of interest.