ESMO 2019 — Combination of cediranib and olaparib has clinical benefit in BRCA wild-type platinum-resistant ovarian cancer


  • Jo Whelan
  • Oncology Conference reports
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Takeaway

  • Heavily pretreated patients with platinum-resistant ovarian cancer (PROC) experienced clinical benefit with combination of cediranib and olaparib.
  • This oral regimen may offer an alternative to chemotherapy.

Why this matters

  • PROC is an area of high unmet need: median PFS is only 3-4 months even after weekly paclitaxel, which is currently the most effective chemotherapy regimen.
  • Single-agent PARP inhibition (olaparib) has limited efficacy in BRCA-wild-type PROC. Hypoxia induced by antiangiogenic agents might sensitise these tumours to PARP inhibition.

Key results

  • Median PFS was 5.7 months for the continuous cediranib/olaparib arm, 3.8 months for the intermittent schedule arm, and 3.1 months for the paclitaxel control arm.
  • The 1.82 month difference in PFS between paclitaxel and the continuous schedule was statistically significant in BRCA wild-type/unknown patients (95% CI 0.4-3.5 months, P=0.03) when analysed using the difference in area under the PFS curve.
  • 84.6% of evaluable patients (n=39) on the continuous schedule experienced clinical benefit (stable disease or better by RECIST 1.1), compared with 54.1% of patients in the paclitaxel arm (n=24 evaluable).
  • The combination of cediranib and olaparib was well-tolerated, and severe diarrhoea occurred in only 5% of patients on the continuous schedule.

Study design

  • 123 patients were randomised 1:1:1 to receive either 80 mg/m2 weekly paclitaxel for up to 24 weeks (control); or olaparib 300 mg twice daily together with either 20 mg cediranib daily (continuous schedule) or 20 mg cediranib 5 days per week (intermittent schedule), until progression. The primary endpoint was PFS.
  • The study patients were heavily pre-treated: 59% had received three or more prior lines of chemotherapy, and median platinum-free interval was less than 3 months.
  • 82% had wild-type BRCA status and a further 7% had unknown BRCA status.
  • Funding: AstraZeneca.

Limitations

  • Patient numbers were small, meaning that the trial was underpowered.

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