Immune checkpoint inhibition improves PFS in non-BRCA-mutated ovarian cancer

Patients with newly diagnosed advanced ovarian cancer without BRCA mutations who received durvalumab and olaparib in addition to the standard-of-care had improved progression-free survival (PFS) compared with those who received the standard-of-care only, according to the interim results of the DUO-O trial.

Maintenance therapy with the PARP inhibitor olaparib has improved outcomes of first-line treatment of advanced ovarian cancer [1]. However, unmet needs remain, especially in non-BRCA-mutated patient subgroups. Recently, the phase 2 MEDIOLA study (NCT02734004) showed promising clinical activity of durvalumab/bevacizumab/olaparib maintenance treatment in patients with non-germline BRCA mutation [2].

The current phase 3 DUO-O study (NCT03737643) evaluates first-line treatment with chemotherapy/bevacizumab/durvalumab followed by bevacizumab/durvalumab/olaparib maintenance therapy in patients with newly diagnosed non-BRCA-mutated advanced ovarian cancer. Dr Philipp Harter (Kliniken Essen-Mitte, Germany) presented the results of the first, pre-planned interim analysis [3].

A total of 1,120 participants (FIGO stage III–IV, non-BRCA mutation) were randomised 1:1:1 to Arm 1: chemotherapy/bevacizumab (6 cycles) followed by bevacizumab (total of 15 months); Arm 2: chemotherapy/bevacizumab/durvalumab followed by bevacizumab/durvalumab (24 months); or Arm 3: chemotherapy/bevacizumab/durvalumab followed by bevacizumab/durvalumab/olaparib (24 months). The primary endpoint was PFS in Arm 3 versus Arm 1 (in HRD-positive and intention-to-treat [ITT] cohorts, respectively).

In the HRD-positive population, the median PFS was significantly higher in Arm 3 compared with Arm 1 (37.3 vs 23.0 months; HR 0.49; P<0.0001). In the HRD-negative population, the median PFS was also significantly higher in Arm 3 compared with Arm 1 (20.9 vs 17.4 months; HR 0.68; P<0.0001).

In the ITT population, the median PFS was higher in Arm 3 versus Arm 1 (24.2 vs 19.3 months; HR 0.63; P<0.0001). The PFS benefit in Arm 3 versus Arm 1 was not affected by age, performance status, stage of disease, or PD-L1 expression. Moreover, a numerical but not statistical improvement in median PFS was observed in Arm 2 versus Arm 1: 20.6 versus 19.3 months (HR 0.87; P=0.13).

Discontinuation due to adverse events was more often observed in Arm 3 compared with Arm 1: 35% versus 20% overall, and 26% versus 13% during maintenance treatment.

“DUO-O met its primary endpoint, demonstrating statistically significant and clinically meaningful improvement in PFS with first-line chemotherapy/bevacizumab/durvalumab followed by maintenance bevacizumab/durvalumab/olaparib compared with chemotherapy/bevacizumab followed by maintenance bevacizumab,” concluded Dr Harter.

1. DiSilvestro P, et al. J Clin Oncol. 2023;41:609–617.


2. Bannerjee S, et al. Ann Oncol. 2022;33(suppl_7):S235–S282.


3. Harter P, et al. Durvalumab with paclitaxel/carboplatin and bevacizumab followed by maintenance durvalumab, bevacizumab and Olaparib in patients with newly diagnosed advanced ovarian cancer without a tumour BRCA1/BRACA2 mutation: results from the randomized, placebo-controlled phase III DUO-O/ENGOT-ov46/AGO-OVAR 23/GOG-3025 trial. Abstract LBA5506. ASCO Annual Meeting 2023, 2–6 June, Chicago, USA.

 

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Posted on 1 August, 20231 August, 2023