CONFERENCE UPDATE: ASCO 2023

Addition of olaparib and durvalumab to current SOC may improve PFS in patients with advanced OC without BRCA1/2 mutation

ONCOLOGY OBSTETRICS & GYNECOLOGY
18 Aug 2023

STUDY DESIGN

The combination of olaparib and bevacizumab as first-line maintenance therapy has demonstrated improved outcomes in advanced ovarian cancer (OC).1 Yet, the unmet needs remain among patients without breast cancer (BRCA) mutations.1 In the phase 2 MEDIOLA study, the clinical benefits of the combined therapy of bevacizumab, durvalumab, and olaparib among platinum-sensitive advanced OC patients without germline BRCA1/2 mutation were demonstrated, indicating the potential of applying immuno-oncology agents for improving the outcomes of these specific advanced OC patient subgroups.1

The DUO-O study is a randomized, phase 3 study designed to investigate the safety and efficacy of paclitaxel/carboplatin + bevacizumab + durvalumab followed by maintenance therapy with bevacizumab + durvalumab + olaparib in adult patients with newly diagnosed, International Federation of Gynecology and Obstetrics (FIGO) stage III to IV high-grade epithelial non-tumor BRCA mutation (tBRCAm) advanced OC.1 The patients did not receive prior systemic therapy for OC and were naïve to poly (ADP‐ribose) polymerase (PARP) inhibitors and immunotherapies.1 A total of 1,130 participants were recruited and randomized 1:1:1 into 3 arms: Arm 1 patients received chemotherapy + bevacizumab + durvalumab placebo, followed up with a 15-month maintenance therapy of bevacizumab + durvalumab placebo + olaparib placebo; arm 2 patients received chemotherapy + bevacizumab + durvalumab, followed up with a 15-month maintenance therapy of bevacizumab + a 24-month therapy of durvalumab + olaparib placebo; and arm 3 patients received chemotherapy + bevacizumab + durvalumab, followed up with a 15-month maintenance therapy of bevacizumab + 24-month therapies of durvalumab + olaparib.1 The treatment was continued until disease progression or treatment completion.1  The primary endpoint was progression-free survival (PFS), determined by Response Evaluation Criteria in Solid Tumors (RECIST) per investigator in arm 3 vs. arm 1.1 The positive preplanned PFS analysis was presented in the 2023 ASCO annual meeting.1 The DUO-O trial is still ongoing.1

FINDINGS

 Primary endpoint:
  • The primary endpoints were the difference in PFS between arm 1 and arm 3, particularly the non-tBRACm homologous recombination deficiency (HRD)-positive and intention-to-treat (ITT) populations in each arm1
  • The non-tBRCAm HRD-positive population in arm 3 (n=140) had a significantly longer median PFS than that in arm 1 (n=143) (37.3 vs. 23.0 months; HR=0.49; 95% CI: 0.34-0.69; p<0.001)1
  • As to the HRD-negative subgroup, arm 3 also demonstrated a significantly longer PFS than that in arm 1 (20.9 vs. 17.4 months; HR=0.68; 95% CI: 0.54-0.86)1
  • Similarly, the ITT population in arm 3 (n=378) exhibited a significantly longer median PFS compared with the ITT population in arm 1 (n=378) (24.2 vs. 19.3 months; HR=0.63; 95% CI: 0.52-0.76; p<0.0001)1
Secondary endpoints:
  • The secondary endpoints included the PFS difference between arm 1 and arm 2, and overall survival (OS)1
  • Results indicated that patients in arm 2 had similar PFS vs. patients in arm 1 (20.6 vs. 19.3 months; HR=0.87; 95% CI: 0.73-1.04; p=0.13)1
Safety:
  • Overall, the safety profile was generally consistent with previous studies for each agent1
  • Grade ≥3 neutropenia occurred in 31% of patients in arm 3 and 26% in arm 1 throughout the study. The rates of grade ≥3 neutropenia were lower during the maintenance phase, with 9% and 2% in arm 3 and arm 1, respectively1

 

“We observe statistically significant and clinically meaningful improvements in PFS with first-line chemotherapy + bevacizumab + durvalumab, accompanied with a combined maintenance therapy of bevacizumab + durvalumab + olaparib”

Dr. Philipp Harter
Department of Gynecology & Gynecologic Oncology,
Evangelische Kliniken Essen-Mitte,
Essen, Germany

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