Reference Detail

Ref Type

Journal Article

PMID

(35737919)

Authors

Rosenberg JE, Park SH, Kozlov V, Dao TV, Castellano D, Li JR, Mukherjee SD, Howells K, Dry H, Lanasa MC, Stewart R, Bajorin DF

Title

Durvalumab Plus Olaparib in Previously Untreated, Platinum-Ineligible Patients With Metastatic Urothelial Carcinoma: A Multicenter, Randomized, Phase II Trial (BAYOU).

Journal	Vol	Issue	Date	Pages	Journal Short Title
Journal of clinical oncology : official journal of the American Society of Clinical Oncology			2022 Jun 23	43-53	J Clin Oncol

URL

Abstract Text

Homologous recombination repair gene mutations (HRRm) are common in urothelial carcinoma (UC), rendering tumor cells sensitive to poly (ADP-ribose) polymerase (PARP) inhibition. We assessed efficacy and safety of durvalumab (anti-programmed cell death ligand-1) plus olaparib (PARP inhibitor) in patients with metastatic UC (mUC).This randomized, multicenter, double-blind, phase II trial enrolled untreated, platinum-ineligible patients with mUC. Patients (N = 154) were randomly assigned 1:1 to receive durvalumab (1,500 mg intravenously once every 4 weeks) plus olaparib (300 mg orally, twice daily) or durvalumab plus placebo. The primary end point was progression-free survival (PFS) assessed by investigators per RECIST version 1.1. Secondary end points included overall survival in all patients and PFS in patients with HRRm.Overall, median PFS was 4.2 months (95% CI, 3.6 to 5.6) for durvalumab plus olaparib and 3.5 months (95% CI, 1.9 to 5.1) for durvalumab plus placebo (hazard ratio [HR], 0.94; 95% CI, 0.64 to 1.39; log-rank P value, .789). Median overall survival was 10.2 months (95% CI, 7.0 to 13.9) and 10.7 months (95% CI, 7.2 to 17.3), respectively (HR, 1.07; 95% CI, 0.72 to 1.61). In the 20% of patients with HRRm, median PFS was 5.6 months (95% CI, 1.9 to 8.1) and 1.8 months (95% CI, 1.7 to 2.2), respectively (HR, 0.18; 95% CI, 0.06 to 0.47). Treatment-related grade 3 or 4 adverse events occurred in 18% and 9% of patients, respectively.Adding olaparib to durvalumab did not improve survival outcomes in an unselected mUC population. Efficacy outcomes with durvalumab were similar to those reported for other anti-programmed cell death-1/programmed cell death ligand-1 agents. However, the results of secondary analyses suggest a potential role for PARP inhibition in patients with UC harboring HRRm.

Filtering

Case insensitive filtering will display rows if any text in any cell matches the filter term
Use simple literal full or partial string matches
Separate multiple filter terms with a space. Any order may be used (i. e. a b c and c b a are equivalent )
Filtering will only apply to rows that are already loaded on the page. Filtering has no impact on query parameters.
Use quotes to match on a longer phrase with spaces (i.e. "mtor c1483f")

Sorting

Generally, the default sort order for tables is set to be first column ascending; however, specific tables may set a different default sort order.
Click on any column header arrows to sort by that column
Hold down the Shift key and click multiple columns to sort by more than one column. Be sure to set ascending or descending order for a given column before moving on to the next column.

Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
ATM inact mut	transitional cell carcinoma	predicted - sensitive	Durvalumab + Olaparib	Case Reports/Case Series	Actionable	In a Phase II trial (BAYOU), Lynparza (olaparib) and Imfinzi (durvalumab) improved median progression-free survival (5.6 vs 1.8 mo, HR 0.18) compared to Imfinzi (durvalumab) and placebo in a subgroup of patients with metastatic urothelial carcinoma harboring inactivating mutations in DNA damage repair genes (n=17), with 8.5% of the tumors harboring ATM inactivating mutations (PMID: 35737919; NCT03459846).	35737919