Incorporating Durvalumab and Olaparib Into Ovarian Cancer Treatment Improves PFS

Adding durvalumab to first-line therapy and incorporating durvalumab and olaparib into maintenance therapy improves progression-free survival (PFS) in patients with ovarian cancer, according to research presented at the ASCO Annual Meeting 2023.

Patients who received first-line treatment with paclitaxel, carboplatin, bevacizumab, and durvalumab, followed by maintenance with bevacizumab, durvalumab, and olaparib had significantly better PFS than patients who received first-line treatment with paclitaxel, carboplatin, and bevacizumab, followed by bevacizumab maintenance alone.

These results come from the phase 3 DUO-O trial (ClinicalTrials.gov Identifier: NCT03737643). The trial included 1130 patients with stage III-IV, high-grade, epithelial ovarian cancer whose tumors did not have BRCA1/2 mutations. The patients had received no prior systemic therapy but had undergone primary debulking or planned interval debulking surgery. 

The patients were randomly assigned to 1 of 3 treatment arms:

• In arm 1 (n=378), patients received paclitaxel, carboplatin, and bevacizumab, followed by maintenance with bevacizumab for 15 months.
• In arm 2 (n=374), patients received paclitaxel, carboplatin, bevacizumab, and durvalumab, followed by maintenance with bevacizumab for 15 months and durvalumab for 24 months.
• In arm 3 (n=378), patients received paclitaxel, carboplatin, bevacizumab, and durvalumab, followed by maintenance with bevacizumab for 15 months, durvalumab for 24 months, and olaparib for 24 months.

Baseline characteristics were similar across the arms. Overall, about 90% of patients completed all planned cycles of chemotherapy and started maintenance. The median follow-up was 25.5 months in arm 1, 23.1 months in arm 2, and 23.3 months in arm 3.

The primary endpoint was PFS in arm 1 compared with arm 3 in both the homologous recombination-deficient (HRD) population and the intent-to-treat (ITT) population. In both populations, patients in arm 3 had significantly longer median PFS than patients in arm 1. 

In the HRD population, the median PFS was 23.0 months in arm 1 and 37.3 months in arm 3 (hazard ratio [HR], 0.49; 95% CI, 0.34-0.69; P <.0001). The 24-month PFS rate was 46% and 70%, respectively.

In the ITT population, the median PFS was 19.3 months in arm 1 and 24.2 months in arm 3 (HR, 0.63; 95% CI, 0.52-0.76; P <.0001). The 24-month PFS rate was 32% and 51%, respectively.

The PFS benefit in arm 3 was observed across subgroups, including in the HRD-negative population. In this group, the median PFS was 17.4 months in arm 1 and 20.9 months in arm 3 (HR, 0.68; 95% CI, 0.54-0.86).

“DUO-O made its primary endpoint at the planned PFS interim analysis, demonstrating a statistically significant and clinically meaningful improvement in progression-free survival with first-line carboplatin, paclitaxel, bevacizumab, and durvalumab, followed by maintenance with bevacizumab, durvalumab, and olaparib,” said study presenter Philipp Harter, MD, PhD, of the Kliniken Essen-Mitte in Essen, Germany.

A secondary endpoint was PFS in the ITT population in arm 2 compared to arm 1. The median PFS was numerically higher in arm 2 than arm 1 (20.6 months and 19.3 months, respectively), but this difference was not statistically significant (HR, 0.87; 95% CI, 0.73-1.04; P =.13).

Safety results were generally consistent with the known profiles of each individual agent, according to Dr Harter. 

Grade 3 or higher adverse events (AEs) occurred in 61% of patients in arm 1, 66% in arm 2, and 71% in arm 3. Grade 3 or higher anemia was more common in arm 3 (24%) than in arm 1 or 2 (8% for both arms).

AEs led to treatment discontinuation in 20% of patients in arm 1, 26% in arm 2, and 35% in arm 3. Fatal AEs occurred in 1%, 2%, and 2%, respectively.

Myelodysplastic syndromes/acute myeloid leukemia occurred in 1 patient in arm 1 and 2 patients in arm 3. New primary malignancies occurred in 1 patient in arm 1, 1 patient in arm 2, and 4 patients in arm 3.

Dr Harter noted that this trial is ongoing. Final PFS, overall survival, and other results will be reported in the future. 

Disclosures: This research was supported by AstraZeneca. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures. 

Reference
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. ASCO 2023. June 2-6, 2023. Abstract LBA5506.

This article originally appeared on Cancer Therapy Advisor