Durvalumab Combo Maintains PFS Benefit in Ovarian Cancer

Durvalumab (Imfinzi) plus chemotherapy and bevacizumab (Avastin), followed by maintenance with olaparib (Lynparza), durvalumab, and bevacizumab, led to improved progression-free survival (PFS) compared with the control arm of chemotherapy and bevacizumab, followed by maintenance bevacizumab. Patients with newly diagnosed advanced ovarian cancer who did not harbor BRCA1/2 mutations were evaluated in the phase 3 DUO-O trial (NCT03737643). The updated results were presented at the 2024 European Society for Medical Oncology Gynaecological Cancers Congress in June.¹

Findings demonstrated that in patients with BRCA-unmutated, homologous recombination deficient (HRD)–positive disease, the median PFS was 45.1 months in the treatment arm (arm 3; n = 140) compared with 23.3 months for patients treated in the control arm (arm 1; n = 143; HR, 0.46; 95% CI, 0.33-0.65). Patients treated with durvalumab plus chemotherapy and bevacizumab, followed by maintenance durvalumab plus bevacizumab (arm 2; n = 148) achieved a median PFS of 25.1 months (HR vs arm 1, 0.89; 95% CI, 0.67-1.19).

In the BRCA-unmutated, intention-to-treat (ITT) population, the median PFS was 25.1 months for arm 3 (n = 578) vs 19.3 months for arm 1 (n = 378; HR, 0.61; 95% CI, 0.51-0.73). The median PFS for arm 2 (n = 374) was 20.6 months (HR vs arm 1, 0.87; 95% CI, 0.74-1.03; P = .11).

“DUO-O continues to demonstrate a clinically meaningful PFS benefit with first-line durvalumab, chemotherapy, and bevacizumab, followed by durvalumab, bevacizumab, and olaparib maintenance [in arm 3] vs the control [arm 1],” Fabian Trillsch, MD, deputy director of Polyclinic for Gynecology and Obstetrics at Ludwig-Maximilians-University of Munich Hospital in Germany, stated during the presentation.

Notably, at a previously planned interim PFS analysis presented during the 2023 American Society of Clinical Oncology Annual Meeting, investigators shared that the investigational approach led to a statistically significant improvement in PFS compared with the control.²

Patients with HRD-positive disease had a median PFS of 37.3 months in arm 3 compared with 23.0 months in arm 1 (HR, 0.49; 95% CI, 0.34-0.69; P < .0001). In the ITT population, the median PFS was 24.2 months in arm 3 vs 19.3 months in arm 1 (HR, 0.63; 95% CI, 0.52-0.76; P < .0001).

The updated data included results from the final PFS analysis and an interim OS analysis, as well as an analysis of time to second progression (PFS2).¹

DUO-O enrolled patients with newly diagnosed, FIGO stage III to IV high-grade epithelial ovarian cancer who did not harbor BRCA mutations, were treatment-naive, and had undergone primary debulking or planned interval debulking surgery.²

The study included a run-in featuring treatment with carboplatin plus paclitaxel during cycle 1 before patients were randomly assigned 1:1:1. After the chemotherapy phase in each randomized arm, patients with a response, stable disease, or no evidence of disease were allowed to receive maintenance therapy. In arm 1, patients received carboplatin and paclitaxel plus bevacizumab prior to maintenance bevacizumab. Patients in arm 2 received durvalumab plus carboplatin, paclitaxel, and bevacizumab, followed by bevacizumab and durvalumab in the maintenance phase. In arm 3, patients received durvalumab plus carboplatin, paclitaxel, and bevacizumab, followed by maintenance bevacizumab, durvalumab, and olaparib.²

The primary end point of the study was PFS per RECIST 1.1 criteria for arm 3 vs arm 1 in the HRD-positive and ITT populations. Key secondary end points included OS, PFS2, and safety.²

The final PFS analysis was scheduled to be performed when PFS data in arms 3 and 1 reached 58% maturity in the HRD-positive population and 62% in the ITT population.²

“In line with a previous analysis, we observed a PFS benefit for arm 3 vs arm 1 across the prespecified subgroup analysis in the BRCA-unmutated, HRD-positive population, [based on] stratification factors and other clinically relevant factors,” Trillsch reported. “Similarly, a PFS benefit for arm 3 vs arm 1 was also seen across the predefined subgroups in the BRCA-unmutated ITT population.”

In the HRD-positive population, the median OS was not reached (NR) in all 3 arms; however, trends favoring arm 3 vs arm 1 (HR, 0.84; 95% CI, 0.51-1.37; P = .48) and arm 2 vs arm 1 (HR, 0.69; 95% CI, 0.41-1.15) were observed. In the ITT population, the median OS was 48.5 months in arm 3 vs 48.0 months in arm 1 (HR, 0.95; 95% CI, 0.76-1.20; P = 0.68). The median OS was NR in arm 2 (HR vs arm 1, 0.92; 95% CI, 0.73-1.16; P = .48).²

In the HRD-positive cohort, the median PFS2 was NR for arm 3 vs 42.0 months for arm 1 (HR, 0.62; 95% CI, 0.40-0.95). The median PFS2 was 48.3 months in arm 2 (HR vs arm 1, 0.91; 95% CI, 0.60-1.36). In the ITT cohort, the median PFS2 was 35.4 months in arm 3 vs 32.8 months in arm 1 (HR, 0.82; 95% CI, 0.67-1.01). The median PFS2 was 33.2 months in arm 2 (HR vs arm 1, 0.91; 95% CI, 0.75-1.12).²

Regarding safety, findings were consistent with the primary analysis of the study, according to investigators. The most common grade 3 or higher adverse events in arm 3 were neutropenia (31%; arm 2, 28%; arm 1, 26%) and anemia (25%; 8%; 8%, respectively).²

“DUO-O is ongoing, and further insight into the long-term benefit of the combination will be provided with additional follow-up,” Trillsch concluded.

REFERENCES:
1. Trillsch F, Okamoto A, Kim JW, et al. Durvalumab + carboplatin/paclitaxel + bevacizumab followed by durvalumab, bevacizumab + olaparib maintenance for newly diagnosed advanced ovarian cancer without a tumour BRCA1/ BRCA2 mutation: updated results from DUO-O. Ann Oncol. 2024;9(suppl 5):1-19. doi:10.1016/esmoop/esmoop103501

2. Harter P, Trillsch F, Okamoto A, et al. Durvalumab with paclitaxel/carboplatin (PC) and bevacizumab (bev), followed by maintenance durvalumab, bev, and olaparib in patients (pts) with newly diagnosed advanced ovarian cancer (AOC) without a tumor BRCA1/2 mutation (non-tBRCAm): results from the randomized, placebo (pbo)-controlled phase III DUO-O trial. J Clin Oncol. 2023;41(suppl 17):LBA5506. doi:10.1200/ JCO.2023.41.17_suppl.LBA5506