The DUO-E trial

Professor Jean-François Baurain, medical oncologist at the Cliniques Universitaires Saint-Luc, presents the data of the DUO-E trial in endometrial cancer at the SGO congress.

This clinical trial, involving over 700 patients, evaluates the efficacy of checkpoint inhibition as a first-line treatment for endometrial cancer. The study comprises three arms: (A) standard chemotherapy with carboplatin-paclitaxel, (B) chemotherapy combined with durvalumab and maintenance therapy with durvalumab, and lastly (C) maintenance therapy with durvalumab alongside olaparib post-chemotherapy and durvalumab treatment.

Previous data presentations have demonstrated the advantageous effects of durvalumab and durvalumab plus olaparib compared to chemotherapy alone, particularly in terms of PFS comparing A and B and comparing A and C. At the ESGO conference, Professor Baudain presented data concerning the classification of the MMR status.

In dMMR patients, the addition of durvalumab to chemotherapy significantly improves the response rate, with an almost 60% increase, including a 12% increase in complete responders. Additionally, there is a notable absolute 20% benefit in OS at 18 months. The addition of olaparib does not substantially alter these outcomes.

This trial reaffirms earlier findings that dMMR patients should receive chemotherapy alongside durvalumab. Whether chemotherapy can be omitted in this subgroup is a question being addressed by ongoing trials.

Approximately 80% of endometrial cancers are pMMR patients, and even in this subgroup, the addition of durvalumab to chemotherapy positively influences response rates, PFS, and OS.

While the primary aim of the study wasn’t to directly compare A and C, with the addition of olaparib, the data reveal a significant improvement in PFS, with an increase of nearly 6 months. Although the response rate remains around 60%, there’s an enhancement in the quality of response, marked by an absolute gain of a 5% increase in complete responders and a prolonged duration of response. Consequently, an improvement in PFS and other surrogate endpoints is observed. Despite only having a 30% maturity of data, the HR for OS was 0.69.

The principal takeaway from the DUO-E trial is that MSI patients should receive chemotherapy alongside durvalumab, while MSS patients should receive both durvalumab and olaparib.