KEY TAKEAWAYS
- The DUO-E phase 3 trial aimed to present OS, TFST, PFS2, and TSST as a secondary endpoint in ITT and MMR subgroup analyses.
- The results showed consistently favored experimental arms over CP. MMR subgroup analysis highlighted benefits.
The Phase III DUO-E trial (NCT04269200) showcased significant and clinically meaningful progression-free survival (PFS) enhancement in endometrial cancer (EC) patients. Addition of durvalumab to carboplatin/paclitaxel (CP), followed by durvalumab ± olaparib, surpassed CP alone.
Interim overall survival (OS) analyses in the intent-to-treat (ITT) population demonstrated substantial improvement with the experimental arms. Exploratory analyses by MMR status (deficient [dMMR] and proficient [pMMR]) revealed PFS benefits in both subgroups, with maintenance olaparib further enhancing outcomes in pMMR patients.
Jean-Francois Baurain to present OS, time to first subsequent treatment (TFST), time to second progression (PFS2), and time to second subsequent treatment (TSST) outcomes in both ITT and MMR subgroup analyses.
Patients with newly diagnosed FIGO Stage III/IV or recurrent EC, untreated with first-line systemic therapy, were randomized 1:1:1. They received either CP (CP + durvalumab placebo [pbo; 6 cycles] followed by durvalumab pbo + olaparib pbo), CP+D (CP + durvalumab [1120 mg IV q3w; 6 cycles] followed by durvalumab [1500 mg IV q4w] + olaparib pbo), or CP+D+O (CP + durvalumab [6 cycles] followed by durvalumab + olaparib [300 mg tablets bid]). OS, TFST, PFS2, and TSST were secondary endpoints. Subgroup analyses of OS, TFST, PFS2, and TSST by MMR status were exploratory.
Among 718 randomized patients, 80.1% were pMMR and 19.9% were dMMR. At the primary data cut-off (12 April 2023), interim OS subgroup analysis for the pMMR subgroup indicated a trend toward benefit for CP+D vs CP (HR [95% CI]: 0.91 [0.64–1.30]), which was enhanced for CP+D+O vs CP (HR [95% CI]: 0.69 [0.47–1.00]).
In dMMR patients, OS improvement was observed for both experimental arms vs CP (HR [95% CI] for CP+D vs CP: 0.34 [0.13–0.79]; CP+D+O vs CP: 0.28 [0.10–0.68]). TFST, PFS2, and TSST analyses indicated a trend toward benefit in both experimental arms vs CP in the ITT population and MMR subgroups.
In pMMR patients, TFST, PFS2, and TSST demonstrated benefit for CP+D vs CP (all HRs <1.00), which was enhanced for CP+D+O vs CP (all HRs <0.70). The greatest benefit with the addition of durvalumab to CP followed by durvalumab±olaparib vs CP alone was observed in the dMMR subgroup (all HRs <0.45). The safety profiles of the treatment arms were generally consistent with individual components.
Secondary efficacy endpoints in the ITT population consistently favored both experimental arms over CP. Exploratory analyses by MMR subgroup demonstrated significant benefit with durvalumab addition to CP, followed by durvalumab±olaparib, particularly in dMMR patients.
Furthermore, the inclusion of maintenance olaparib in the CP+D+O arm consistently augmented secondary efficacy benefits in patients with pMMR EC. Funding was provided by AstraZeneca.
Source: https://sgo.planion.com/Web.User/AbstractDet?ACCOUNT=SGO&ABSID=578958&CONF=AM2024&CKEY=
Clinical Trial: https://clinicaltrials.gov/study/NCT04269200
Baurain JF, Chon HS, Sundborg MJ, et al. (2024) “Durvalumab plus carboplatin/paclitaxel followed by durvalumab with or without olaparib as a first‑line treatment for endometrial cancer: Overall survival and additional secondary efficacy endpoints by mismatch repair status in the DUO-E/GOG-3041/ENGOT-EN10 Trial.” Presented at SGO 2024.
