Phase II DORA Study of Olaparib with or without Durvalumab as a Chemotherapy-Free Maintenance Strategy in Platinum-Pretreated Advanced Triple-Negative Breast Cancer

Clinical Cancer Research Manuscript
Authors Tira J. Tan, Sarah Sammons, Young-Hyuck Im, Lilin She, Kelly Mundy, Robert Bigelow, Tiffany A. Traina, Carey Anders, Joe Yeong, Ezequiel Renzulli, Sung-Bae Kim, and Rebecca Dent


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 and Methods

In the phase II non-comparative DORA trial (NCT03167619), patients with ongoing stable disease (SD) or complete/partial response (CR/PR) from first- or second-line platinum-based chemotherapy for TNBC (≤10% estrogen/progesterone receptor expression) were randomized 1:1 to receive olaparib 300 mg twice daily with or without durvalumab 1500 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.


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% 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 (= 0.0023 and < 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.


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.