Olaparib Plus Ceralasertib in Metastatic Triple-Negative Breast Cancer: VIOLETTE Trial

At the ESMO Breast Cancer Congress held in Berlin from May 3 to 5, 2022, results were presented for the VIOLETTE Phase 2 clinical trial. This study investigated the efficacy and safety of combining Olaparib (a PARP inhibitor) with Ceralasertib (an ATR inhibitor) in patients with previously treated metastatic triple-negative breast cancer (TNBC).

Study Design: VIOLETTE Trial

The VIOLETTE trial randomized patients with metastatic TNBC who had failed at least one prior line of therapy into two main arms:

1. Olaparib Monotherapy
2. Olaparib + Ceralasertib Combination

The primary endpoint was progression-free survival (PFS).

Key Results

The study results showed a modest numerical improvement in PFS with the combination, but the overall benefit remained limited:

• Median PFS: 5.3 months for the Olaparib + Ceralasertib group vs. 3.6 months for the Olaparib monotherapy group.
• Objective Response Rate (ORR):
  • BRCA Mutation Patients: 50.0% (Combination) vs. 44.2% (Monotherapy).
  • HRR Mutation Patients: 20.0% (Combination) vs. 15.0% (Monotherapy).
  • Non-HRR Mutation Patients: 15.4% (Combination) vs. 3.9% (Monotherapy).

While the combination showed some activity in patients without homologous recombination repair (HRR) mutations, it did not provide a significant clinical breakthrough for the broader population.

Safety Profile

Common adverse events included anemia and neutropenia. Grade 3 or higher adverse events occurred in 46.8% of patients in the combination group compared to 35.5% in the monotherapy group.

Conclusion

Dr. Suzette Delaloge from Institut Gustave Roussy noted that while basic research suggested synergy between PARP and ATR inhibition, the VIOLETTE trial did not demonstrate a substantial clinical benefit for pre-treated metastatic TNBC patients with BRCA mutations. However, the signals observed in patients without HRR mutations suggest that ATR inhibition may have independent antitumor activity worth further exploration.

Source: ESMO Daily Reporter - VIOLETTE Trial Highlights

#BreastCancer #TNBC #Olaparib #Ceralasertib #PARPInhibitor #ATRInhibitor #CancerResearch

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