Oncology · 1 h ago
VIOLETTE finds no PFS benefit from ceralasertib plus olaparib in advanced TNBC
In the randomized phase II VIOLETTE study, 273 patients with previously treated, PARP inhibitor–naïve advanced triple-negative breast cancer were assigned to olaparib alone or one of two combinations. Ceralasertib plus olaparib improved response rates in the non-HRR-mutated subgroup, but did not significantly improve progression-free survival in any molecular stratum.
- Ceralasertib plus olaparib did not significantly improve PFS.
- Response rates rose in non-HRR-mutated disease.
- Adavosertib plus olaparib was stopped for toxicity.
VIOLETTE (NCT03330847) evaluated second- or third-line treatment in patients with advanced or metastatic triple-negative breast cancer who had not previously received a PARP inhibitor. Patients were randomized to olaparib alone, ceralasertib plus olaparib, or adavosertib plus olaparib. The primary endpoint was progression-free survival (PFS) assessed by blinded independent central review. The adavosertib combination arm was stopped early because of unacceptable toxicity.
Among 273 randomized patients, 114 received olaparib, 112 received ceralasertib plus olaparib, and 47 entered the adavosertib arm. Median PFS with ceralasertib plus olaparib was 7.4 months in patients with BRCA1/2 mutations, 3.9 months in those with non-BRCA homologous recombination repair (HRR) mutations, and 3.6 months in the non-HRR-mutated group. These results did not differ significantly from olaparib alone. In the non-HRR-mutated subgroup, objective response was 15.4% with the combination versus 3.9% with olaparib alone (P=0.0425). No unexpected safety signals were reported for ceralasertib or olaparib. The phase II response-rate finding did not coincide with a PFS improvement, limiting its clinical significance; the results do not establish a treatment change.
In practice
For patients with previously treated, PARP inhibitor–naïve advanced triple-negative breast cancer, this randomized phase II study did not show a significant PFS advantage for ceralasertib plus olaparib over olaparib alone in any molecular stratum. The higher objective response rate in the non-HRR-mutated subgroup is a preliminary signal, but it was not accompanied by improved PFS and does not establish a practice-changing benefit. Applicability is limited to the studied population and treatment setting.
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Clinical Cancer Research: Safety and Efficacy of Ceralasertib plus Olaparib for Advanced/Metastatic Triple-Negative Breast Cancer in Three Molecular Strata: The Phase II VIOLETTE Study ↗This is an automated AI-condensed summary that has not yet been reviewed by an editor. Always consult the full item at the original source.