Phase II DORA study of olaparib with or without durvalumab as a chemotherapy-free maintenance strategy in platinum-pretreated advanced triple-negative breast cancer Journal Article
| Authors: | Tan, T. J.; Sammons, S.; Im, Y. H.; She, L.; Mundy, K.; Bigelow, R.; Traina, T. A.; Anders, C.; Yeong, J.; Renzulli, E.; Kim, S. B.; Dent, R. |
| Article Title: | Phase II DORA study of olaparib with or without durvalumab as a chemotherapy-free maintenance strategy in platinum-pretreated advanced triple-negative breast cancer |
| 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 and Methods: 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 platinumbased chemotherapy for TNBC (≤10% estrogen/progesterone receptor expression) were randomized 1:1 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 platinumbased 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. © 2024 The Authors. |
| Keywords: | adult; clinical article; controlled study; human tissue; treatment response; aged; gene mutation; overall survival; genetics; clinical trial; drug tolerability; fatigue; drug dose reduction; drug safety; drug withdrawal; monotherapy; paclitaxel; chemotherapy; genetic analysis; ovarian neoplasms; carboplatin; cancer immunotherapy; progression free survival; multiple cycle treatment; phase 2 clinical trial; neoplasm recurrence, local; anemia; nausea; randomized controlled trial; estrogen; maintenance therapy; estrogens; monoclonal antibody; coughing; pneumonia; tumor suppressor gene; antibodies, monoclonal; kidney function; multicenter study; tumor recurrence; ovary tumor; platinum; receptors, progesterone; piperazines; progesterone receptor; drug therapy; disease control; piperazine derivative; olaparib; programmed death 1 ligand 1; phthalazine derivative; phthalazines; progesterone; triple negative breast cancer; thyroiditis; humans; human; female; article; durvalumab; loss of appetite; triple negative breast neoplasms; b7-h1 antigen; platinum pretreated advanced chemotherapy |
| Journal Title: | Clinical Cancer Research |
| Volume: | 30 |
| Issue: | 7 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2024-04-01 |
| Start Page: | 1240 |
| End Page: | 1247 |
| Language: | English |
| DOI: | 10.1158/1078-0432.Ccr-23-2513 |
| PUBMED: | 38236575 |
| PROVIDER: | scopus |
| PMCID: | PMC10982642 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
