BAYOU: A phase II, randomized, multicenter, double-blind, study of durvalumab (D) in combination with olaparib (O) for the first-line treatment of platinum-ineligible patients with unresectable, stage IV urothelial carcinoma (UC).
Bibliographic record
Abstract
437 Background: The prognosis for patients (pts) with advanced UC remains poor, particularly for those unable to tolerate platinum-based chemotherapy. Defects in DNA damage repair (e.g., mutations in homologous recombination repair [HRR] genes) are common in UC and render tumor cells sensitive to poly(ADP-ribose) polymerase (PARP) inhibition. HRR gene mutations (HRRm) and PARP inhibition may enhance the antitumor response of immune checkpoint inhibitors. We conducted a randomized phase II study to evaluate D (anti–PD-L1) in combination with O (a PARP inhibitor) or placebo (P) as a first-line treatment for platinum-ineligible pts with unresectable, stage IV UC (BAYOU; NCT03459846). Methods: Eligible pts were an age of ³18 years with an ECOG performance status (PS) of 0, 1, or 2, histologically or cytologically confirmed transitional cell carcinoma, and who had not received prior systemic therapy for unresectable, stage IV disease. Pts were randomized 1:1 to receive D (1500 mg IV q4w) plus O (orally at 300 mg BID) vs D (1500 mg IV q4w) plus O-matching placebo (P). Pts were stratified according to centrally-determined HRR status (mutant vs wild-type) and Bajorin risk index (a composite of visceral metastases and ECOG PS [0, 1 vs 2]). The primary endpoint was progression-free survival (PFS) by RECIST v1.1 (investigator assessed) in the intention-to-treat (ITT) population. Secondary endpoints included overall survival (OS) in the ITT population and PFS in the subset of pts with HRRm. The data cutoff occurred on October 15, 2020. Results: A total of 154 pts were randomized to receive D+O (n = 78) or D+P (n = 76). Among all randomized pts at baseline, 17%, 42%, and 40% had an ECOG PS of 0, 1, or 2, respectively, and 20% had an HRRm. Median PFS was not significantly different between D+O and D+P in the ITT population (Table). In the subset of pts with HRRm, median PFS was 5.6 months in the D+O group and 1.8 months in the D+P group (Table). In the ITT population, median OS (95% CI) was 10.2 months (7.0–13.9) in the D+O group and 10.7 months (7.2–17.3) in the D+P group (HR 1.07, 95% CI 0.72–1.61). Among all treated pts, grade 3 or 4 treatment-related adverse events occurred in 18% and 9% in the D+O and D+P groups, respectively, with one death due to anemia in the D+P group. Conclusions: The BAYOU study did not meet its primary endpoint. However, the results of pre-planned secondary analyses suggest a potential role for PARP inhibition in UC pts harboring HRRm. No new safety signals were observed. Clinical trial information: NCT03459846. [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) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.006 | 0.001 |
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".