Ovarian cancer: novel therapy delays progression

  • Konstantinopoulos PA & et al.
  • Lancet Oncol.
  • 15 Jun 2020

  • curated by Deepa Koli
  • Univadis Clinical Summaries
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Takeaway

  • The addition of berzosertib (an inhibitor of ataxia telangiectasia and rad3-related [ATR] kinase) to gemcitabine in platinum-resistant, high-grade serous ovarian cancer increased PFS vs gemcitabine alone.

Why this matters

  • This is the first randomized study of ATR inhibitor in any tumor type to suggest a benefit to adding an ATR inhibitor to standard chemotherapy in ovarian cancer.

Study design

  • Multicenter, randomized, phase 2 study.
  • 70 patients with recurrent, platinum-resistant, high-grade serous ovarian cancer were randomly assigned to treatment with gemcitabine alone (n=36) or gemcitabine+berzosertib (n=34).
  • Funding: US National Cancer Institute.

Key results

  • The median follow-up was 53.2 weeks in the gemcitabine+berzosertib group and 43.0 weeks in the gemcitabine-alone group.
  • Median PFS was significantly longer with gemcitabine+berzosertib vs gemcitabine alone (22.9 vs 14.7 weeks; HR, 0.57; P=.044).
  • At data cutoff, OS was similar between the groups (HR, 0.84; P=.26).
  • Objective response rate was 11% with gemcitabine alone vs 3% in the combination group.
  • For the gemcitabine-alone group vs the gemcitabine+berzosertib group:
    • The most common treatment-related grade 3-4 adverse events were:
      • Decreased neutrophil count (39% vs 47%).
      • Decreased platelet count (6% vs 24%).
    • Serious adverse events: 28% vs 26%.
    • 1 treatment-related death in both groups (because of sepsis and pneumonitis, respectively).

Limitations

  • Open label.