Phase II DORA Study of Olaparib with or without Durvalumab as a Chemotherapy-Free Maintenance Strategy in Platinum-Pretreated Advanced Triple-Negative Breast Cancer
Mené sur 45 patientes atteintes d'un cancer du sein triple négatif de stade avancé, cet essai de phase II évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité de l'olaparib avec ou sans durvalumab en traitement d'entretien après une chimiothérapie à base de sels de platine
Background: 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. 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% 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.