40MO - First-line (1L) durvalumab + carboplatin/paclitaxel (CP) followed by durvalumab ± olaparib for endometrial cancer (EC) (DUO-E): Objective response rate (ORR), duration of response (DoR) and time to treatment discontinuation or death (TDT) by mismatch repair (MMR) status

Background

DUO-E showed statistically significant and clinically meaningful PFS benefit with CP + durvalumab followed by durvalumab ± olaparib v CP alone (primary endpoints); addition of olaparib conferred enhanced benefit in MMR proficient (pMMR) patients (pts).

Methods

Pts with newly diagnosed FIGO Stage III (measurable disease [RECIST 1.1] before randomization) or IV, or recurrent EC, and naïve to systemic 1L treatment were randomized 1:1:1 to CP + durvalumab placebo (pbo; 6 cycles) followed by durvalumab pbo + olaparib pbo (CP arm); CP + durvalumab (1120 mg IV q3w) followed by durvalumab (1500 mg IV q4w) + olaparib pbo (CP+D arm); or CP + durvalumab followed by durvalumab + olaparib (300 mg bid; CP+D+O arm). ORR, DoR and TDT were assessed in ITT and MMR populations (exploratory).

Results

In the ITT at primary data cutoff (12 Apr 2023), ORRs with CP+D and CP+D+O were improved v CP (62 and 64 v 55%); median (m)DoR and mTDT were longer for CP+D v CP (mDoR: 13.1 [95% CI 6.0–NR] v 7.7 [5.1–13.5] months [mo]; mTDT: 9.9 [8.8–11.2] v 8.8 [7.6–9.7] mo) and further increased with CP+D+O (mDoR: 21.3 [8.1–29.9] mo; mTDT: 15.1 [12.5–18.6] mo; Table). In MMR deficient (dMMR) pts, CP+D and CP+D+O v CP improved ORRs (71 and 73 v 40%), mDoR (NR and 29.9 [95% CI 9.7–29.9] v 10.5 [4.6–NR] mo) and mTDT (21.2 [9.3–NR] and 20.6 [13.4–NR] v 6.7 [5.1–7.9] mo). In pMMR pts, ORRs were similar across arms but mDoR and mTDT were longer with CP+D v CP (mDoR: 10.6 [95% CI 5.6–NR] v 7.6 [5.1–13.1] mo; mTDT: 9.6 [8.1–10.6] v 9.3 [8.0–9.9] mo) and further extended with CP+D+O (mDoR: 18.7 [8.0–NR] mo; mTDT: 13.4 [10.6–15.6] mo).

Conclusions

CP + durvalumab followed by durvalumab ± olaparib improved ORR, DoR and TDT v CP (ITT population). In dMMR pts, CP+D consistently improved ORR, DoR and TDT v CP. In pMMR pts, CP+D improved mDoR v CP and adding olaparib further extended mDoR and mTDT v CP+D.Table: 40MO

*In pts with measurable disease at baseline. CI, confidence interval; IQR, interquartile range; ITT, intent to treat; NR, not reached.

Clinical trial identification

NCT04269200.

Editorial acknowledgment

Medical writing assistance was provided by Rachel Dodd PhD, Cence, funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

E. Van Nieuwenhuysen: Financial Interests, Institutional, Advisory Role: Regeneron, AstraZeneca; Financial Interests, Personal, Advisory Role: Oncoinvent; Financial Interests, Institutional, Other, Travel, Accommodations, Expenses: Regeneron; Financial Interests, Institutional, Funding, Research funding: AstraZeneca, Eli Lilly, Merck, Seagen, Roche, Novartis, Regeneron, Oncoinvent. H.S. Chon: Financial Interests, Personal, Advisory Role: Envision Communications, Eisai; Financial Interests, Personal, Speaker’s Bureau: Clinical Care Options; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Agenus; Financial Interests, Personal, Other, Honoraria: Curio Science, Envision Communications, MJH Healthcare Holdings, LLC, Guidepoint Global. M. Sundborg: Financial Interests, Personal, Full or part-time Employment: GSK; Financial Interests, Personal, Speaker’s Bureau: GSK; Financial Interests, Personal, Other, Honoraria: GSK. M. Gold: Financial Interests, Personal, Other, Travel, Accommodations, Expenses: ASCCP. S.V. Blank: Financial Interests, Personal, Member, 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, Other, Contracted research with institution: AstraZeneca, Acrivon, Merck, Zentalis, GSK, Roche; Financial Interests, Institutional, Other, Research funding: Any Mountain. K.N. Moore: Financial Interests, Personal, Advisory Role: Genentech/Roche, Immunogen, AstraZeneca, VBL Therapeutics, Merck, Eisai, Myriad Genetics, OncXerna Therapeutics, Onconova Therapeutics, Mereo BioPharma, Novartis, Verastem/Pharmacyclics, AADi, Clovis Oncology, Caris Life Sciences, Hengrui Pharmaceutical, Novartis/Pfizer, Iovance Biotherapeutics, aadi, Janssen Oncology, Regeneron, Zentalis; Financial Interests, Institutional, Advisory Role: Mersana, Alkermes, lueprint Medicines, GSK/Tesaro, Duality Biologics; Financial Interests, Personal, Leadership Role: GOG Partners; Financial Interests, Institutional, Leadership Role: NRG Oncology; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: GSK, AstraZeneca; Financial Interests, Personal, Royalties: Up to Date; Financial Interests, Institutional, Other: GOG Partners; Financial Interests, Personal, Other, Honoraria: Research To Practice, Prime Oncology, Physicians' Education Resource, Great Debates and Updates; Financial Interests, Institutional, Funding, Research funding: PTC Therapeutics, Eli Lilly, Merck, Tesaro, Genentech, Clovis Oncology, Lilly Foundation, Regeneron, Bristol Myers Squibb, Verastem, Novartis Pharmaceuticals UK Ltd, AstraZeneca, Agenus, Takeda, Immunogen, Novogen, Artios, Bolt Biotherapeutics, Amgen, Daiichi Sankyo/Lilly, Cyteir, Immunocore. J. Martinez-Garcia: Financial Interests, Personal, Advisory Role: AstraZeneca Spain, GSK; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: PharmaMar, Roche, MSD Oncology. 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, Funding, 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, Accommodations, Expenses: AstraZeneca, Pfizer, Genekor, GSK, MSD. X. Liu: Financial Interests, Personal and Institutional, Stocks/Shares, Stock owner: AstraZeneca; Financial Interests, Personal and Institutional, Full or part-time Employment: 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, Mersana, Nuvectis Pharma, pharma&; Financial Interests, Institutional, Funding, Research funding: AstraZeneca, Novartis, Bayer, Clovis Oncology, Roche/Genentech, GOGFoundation, Mereo BioPharma, Bio-Path Holdings, Inc, GSK, Zentalis, Avenge Bio, Jazz Pharmaceuticals, Nuvectis Pharma. All other authors have declared no conflicts of interest.