Safety and Efficacy of Ceralasertib plus Olaparib for Advanced/Metastatic Triple-Negative Breast Cancer in Three Molecular Strata: The Phase II VIOLETTE Study
Published report from the VIOLETTE trial registered as NCT03330847, in Clinical Cancer Research (2026), chosen as the most cited paper whose own text cites the registry id.
Overview
Purpose: VIOLETTE (NCT03330847) assessed olaparib alone or with ceralasertib (ATR inhibitor) or adavosertib (WEE1 inhibitor) as second-/third-line treatment in three molecular strata of patients with previously treated, PARP inhibitor-naïve, advanced triple-negative breast cancer (TNBC).
Patients and methods: Patients were randomized 1:1:1 to olaparib 300 mg twice daily (BD), ceralasertib 160 mg once daily (Days 1-7; 28-day cycles) + olaparib 300 mg BD, or adavosertib 150 mg BD (Days 1-3, 8-10; 21-day cycles) + olaparib 200 mg BD. Patients were stratified by presence of tumoral homologous recombination repair (HRR) pathway mutations (m): BRCA1/2m, non-BRCA1/2m HRRm, or non-HRRm. Primary endpoint was progression-free survival (PFS) by blinded independent central review.
Results: 273 patients were randomized: 114, 112, and 47 to the olaparib, ceralasertib + olaparib, and adavosertib + olaparib arms, respectively. The adavosertib + olaparib arm was terminated early due to unacceptable toxicity. Median PFS of ceralasertib + olaparib was 7.4, 3.9, and 3.6 months in the BRCA1/2m, non-BRCA1/2m HRRm, and non-HRRm strata, respectively, and did not differ significantly from olaparib (HR 1.02 [90% CI, 0.63-1.66], 0.54 [90% CI, 0.28-1.03], and 0.76 [90% CI, 0.50-1.14], respectively). In the non-HRRm group objective response rates (ORR) were significantly improved for ceralasertib + olaparib (15.4%) vs. olaparib (3.9%; OR, 4.45; 90% CI, 1.30‒21.20; P = 0.0425). No unexpected safety signals were reported for ceralasertib or olaparib.
Conclusions: In patients with advanced PARP inhibitor-naïve non-HRRm TNBC, ceralasertib + olaparib significantly improved ORR versus olaparib. However, clinical significance is limited without improvement in PFS.
Indexed on Europe PMC as PubMed record 42765908 (DOI 10.1158/1078-0432.ccr-26-1066). Its abstract cites the registry id NCT03330847, which is how it was matched to this trial; no figure has been checked by an editor.
This is the paper Europe PMC returns for registry id NCT03330847 with the most citations, so it is the natural first reading for anyone following the VIOLETTE trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.
- Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.