Expert Commentary – Ovarian cancer: main improvements in 2018

  • Ben Gallarda
  • Oncology news
Access to the full content of this site is available only to registered healthcare professionals. Access to the full content of this site is available only to registered healthcare professionals.

Jonathan A Lederman is professor of Medical Oncology in the UCL Cancer Institute and Director of Cancer Research UK and UCL Cancer Trials Centre. He specialises in Gynaecological Cancer treatment and research and has led many national and international clinical trials.

  • Ovarian cancer accounts for 3% of cancer deaths among women and is the most lethal gynaecological malignancy. The five-year survival rate for all stages is around 45% and relapsed ovarian cancer is incurable. Platinum resistance is a major prognostic determinant.
  • For many decades, the treatment of ovarian cancer has involved chemotherapy. The introduction of PARP inhibitors (PARP-i) changed the landscape for this cancer.
  • Maintenance monotherapy with the PARP-i olaparib prolonged progression-free survival (PFS) versus placebo in patients with platinum-sensitive BRCA-mutated recurrent ovarian cancer.
  • More recently, three phase 3 trials (SOLO 2, NOVA and ARIEL 3) demonstrated interesting improvements in PFS with PARP-i olaparib, niraparib and rucaparib in maintenance therapy in patients with both complete or partial response to platinum-based therapy.
  • Testing germline BRCA status is a standard of care in Europe since olaparib has been available. However, the results of NOVA and ARIEL 3 trials, and a broader indication for all three agents irrespective of BRCA or HRD status, suggest diminishing importance of a BRCA mutation as a predictive marker for PARP therapy, even if BRCA remains the most important marker for treatment efficacy.
  • In the near future, we expect to have the results of two placebo-controlled randomised phase 3 trials (PRIMA and SOLO 1) evaluating single-agent maintenance PARP inhibitors in patients with a complete or partial response to platinum therapy. Two other randomised phase 3 trials (ARIEL 4 and SOLO 3) are comparing PARP-i with chemotherapy in the treatment rather than maintenance setting.
  • Other strategies are under evaluation, like combining PARP-i with radiotherapy (as PARP inhibitors increase genomic instability), antiangiogenic agents (hypoxia can increase PARP-i efficacy) and even cancer immunotherapy (ovarian cancer is strongly immunogenic).
  • The question we have to solve for recurrent ovarian cancer is: should we treat it with a PARP inhibitor, chemotherapy or a combination of the two?
  • We can say that chemotherapy remains a key element of treatment, but PARP inhibitors have become central to management.
  • Single-agent PARP-i produce similar results to chemotherapy and maintenance PARP inhibitor in BRCA mutated ovarian cancer. There is an ongoing trial, GYN004, that may tell us if PARP-i can replace chemotherapy. Another trial, QUADRA, informs us of the need for further studies of PARP-i compared to chemo, especially in patients not suited to platinum therapy.
  • An important and open question is now what we will do with PARP inhibitors in later line therapy if we use them more and more in first-line therapy. Combination studies with immunotherapy and antiangiogenic drugs may be the way forward, particularly in situations where chemotherapy drugs are least effective.