Phase II DORA Study of Olaparib with or without Durvalumab as a Chemotherapy-Free Maintenance Strategy in Platinum-Pretreated Advanced Triple-Negative Breast Cancer.
Clin Cancer Res
; 30(7): 1240-1247, 2024 Apr 01.
Article
in En
| MEDLINE
| ID: mdl-38236575
ABSTRACT
PURPOSE:
We explored the efficacy of PARP inhibition with or without programmed death ligand-1 (PD-L1) blockade as chemotherapy-free maintenance therapy for advanced triple-negative breast cancer (aTNBC) sensitive to platinum-based chemotherapy. PATIENTS ANDMETHODS:
In the phase II non-comparative DORA trial (NCT03167619), patients with ongoing stable disease (SD) or complete/partial response (CR/PR) to first- or second-line platinum-based chemotherapy for TNBC (≤10% estrogen/progesterone receptor expression) were randomized 11 to receive olaparib 300 mg twice daily with or without durvalumab 1,500 mg on day 1 every 4 weeks. The primary objective was to compare progression-free survival (PFS) versus a historical control of continued platinum-based therapy.RESULTS:
45 patients were randomized (23 to olaparib alone, 22 to the combination; 3 with estrogen/progesterone receptor expression 1%-10%). At 9.8 months' median follow-up, median PFS from randomization was 4.0 [95% confidence interval (CI), 2.6-6.1] months with olaparib and 6.1 (95% CI, 3.7-10.1) months with the combination, both significantly longer than the historical control (P = 0.0023 and P < 0.0001, respectively). Clinical benefit rates (SD ≥24 weeks or CR/PR) were 44% (95% CI, 23%-66%) and 36% (95% CI, 17%-59%) in the monotherapy and combination arms, respectively. Sustained clinical benefit was seen irrespective of germline BRCA mutation or PD-L1 status, but tended to be associated with CR/PR to prior platinum, particularly in the olaparib-alone arm. No new safety signals were reported.CONCLUSIONS:
PFS was longer than expected with both regimens. A patient subset with wild-type BRCA platinum-sensitive aTNBC had durable disease control with chemotherapy-free maintenance.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Ovarian Neoplasms
/
Piperazines
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Triple Negative Breast Neoplasms
/
Antibodies, Monoclonal
Type of study:
Clinical_trials
Limits:
Female
/
Humans
Language:
En
Journal:
Clin Cancer Res
/
Clin. cancer res
/
Clinical cancer research
Journal subject:
NEOPLASIAS
Year:
2024
Document type:
Article
Affiliation country:
Country of publication: