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.
Bibliographic record
Abstract
LBA5506 Background: Olaparib (ola) maintenance (mtx) improved outcomes in pts with newly diagnosed AOC and a BRCAm (DiSilvestro J Clin Oncol 2023;41:609–17) or with bev in pts with homologous recombination deficiency (HRD+) tumors (Ray-Coquard Ann Oncol 2022: LBA29) in response to 1L treatment, but an unmet need remains. Combining an immune checkpoint inhibitor with an antiangiogenic agent and a PARP inhibitor may enhance antitumor effect (Banerjee Ann Oncol 2022: 529MO). The Phase III DUO-O trial (NCT03737643) evaluates PC + bev + durva, followed by mtx bev + durva + ola, in pts with non-tBRCAm AOC in the 1L setting. Methods: Pts had newly diagnosed FIGO stage III or IV, high-grade epithelial, non-tBRCAm AOC and had completed upfront, or were planned to receive interval, debulking surgery and 1 cycle of PC ± bev. At Cycle 2, pts were randomized 1:1:1 to Arm 1: PC + bev (15 mg/kg IV q3w) + durva pbo (up to 6 cycles) followed by mtx bev (15 mg/kg IV q3w; total 15 months [mo]) + durva pbo (total 24 mo) + ola pbo (total 24 mo); Arm 2: PC + bev + durva (1120 mg IV q3w) followed by mtx bev + durva (1120 mg IV q3w) + ola pbo; or Arm 3: PC + bev + durva followed by mtx bev + durva + ola (300 mg bid tablets). The primary endpoint, progression-free survival (PFS; modified RECIST 1.1 per investigator) in Arm 3 vs Arm 1, was tested first in the non-tBRCAm HRD+ population (GIS ≥42, Myriad MyChoice CDx) and then the intent-to-treat (ITT) population. Results: 1130 pts were randomized: 378 Arm 1, 374 Arm 2, and 378 Arm 3. At a prespecified interim analysis (DCO Dec 5, 2022), a statistically significant improvement in PFS was observed for Arm 3 vs Arm 1: HR 0.49 (95% CI 0.34–0.69; P<0.0001) and HR 0.63 (95% CI 0.52–0.76; P<0.0001) in the HRD+ and ITT populations, respectively; a consistent PFS effect was observed in the HRD- subgroup (HR 0.68, 95% CI 0.54–0.86). A numerical improvement in PFS was shown for Arm 2 vs Arm 1 (ITT population), but statistical significance was not reached (Table). During the study, any serious adverse events were reported in 34%, 43% and 39% of pts in Arms 1, 2 and 3, respectively. Conclusions: PC + bev + durva followed by mtx bev + durva + ola in pts with newly diagnosed non-tBRCAm AOC resulted in a statistically significant and clinically meaningful improvement in PFS vs PC + bev followed by mtx bev. Safety was generally consistent with the known profiles of each agent. Clinical trial information: NCT03737643 . [Table: see text]
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".