What are the most effective maintenance therapies for ovarian cancer?

Updated: Aug 10, 2020
  • Author: Andrew E Green, MD; Chief Editor: Yukio Sonoda, MD  more...
  • Print
Answer

Most patients with ovarian cancer achieve a complete clinical response after debulking surgery and platinum-based chemotherapy. However, 50% experience relapse and ultimately die of the disease. Therefore, strategies to decrease the risk of recurrence have been investigated.

Chemotherapy

A phase III randomized trial exploring the impact of 12 monthly cycles of paclitaxel as maintenance chemotherapy was discontinued by the Data Safety and Monitoring Committee when a prospectively defined interim analysis revealed a highly statistically significant improvement in progression-free survival. [81]

In a subsequent study, however, maintenance paclitaxel demonstrated no overall survival benefit, compared with surveillance. This 3-arm randomized trial included both conventional paclitaxel and a paclitaxel conjugate (paclitaxel linked to a polyglutamate polymer, which achieves higher tissue concentrations of paclitaxel). After a median follow-up of almost 6 years, patients treated with conventional paclitaxel and paclitaxel conjugate had a median overall survival of 51 and 60 months, respectively, compared with 55 months for patients assigned to surveillance with standard follow-up care. [82]

PARP inhibitors

Niraparib (Zejula) is a poly (adenosine diphosphate [ADP]–ribose) polymerase (PARP) enzyme inhibitor that was approved by the FDA in March 2017 for maintenance treatment for recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer in women who are in complete or partial response to platinum-based chemotherapy. Niraparib is active both in patients with and those without BRCA mutations. See Management of Recurrent Disease, below.

Rucaparib (Rubraca) is also a PARP inhibitor. It was initially approved by the FDA as monotherapy for patients with ovarian cancer with a deleterious BRCA mutation following prior treatment with two or more chemotherapies. In April 2018, the FDA approved rucaparib for maintenance treatment of patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy, regardless of BRCA status. 

Maintenance treatment approval was based on findings from the phase 3 ARIEL3 study, which enrolled 564 patients and randomly assigned them to either 600 mg of rucaparib twice daily or placebo. Progression-free survival was 10.8 months in the intention-to-treat population compared with 5.4 months in the placebo group. In the nested BRCA-mutant cohort, the median progression-free survival in patients with a BRCA-mutant carcinoma was 16.6 months for patients receiving rucaparib compared with 5.4 months for the placebo group. [83]

Maintenance treatment with the PARP inhibitor olaparib (Lynparza) resulted in a marked increase in progression-free survival in patients with advanced ovarian cancer who carry a BRCA mutation and have completed successful first-line chemotherapy. A phase III randomized trial in 391 patients found that after a median follow-up of 41 months, the risk of disease progression or death was 70% lower with olaparib than with placebo. [84, 85]

Subgroup analysis of findings from the SOLO-1 trial provided further evidence of the benefit of olaparib for the first-line maintenance treatment of advanced BRCA-mutated ovarian cancer. [58]  Rates of reduction in the risk of disease progression or death with olaparib compared with placebo were as follows:

  • After upfront surgery: 69% (hazard ratio [HR], 0.31; 95% confidence index [CI], 0.21 to 0.46)
  • After interval surgery: 63% (HR, 0.37; 95% CI, 0.24 to 0.58)
  • With residual disease after surgery: 56% (HR, 0.44; 95% CI, 0.25 to 0.77)
  • With no residual disease after surgery: 67% (HR, 0.33; 95% CI, 0.23 to 0.46)
  • With clinical complete response at baseline: 66% (HR, 0.34; 95% CI, 0.24 to 0.47)
  • With clinical partial response at baseline: 69% (HR, 0.31; 95% CI, 0.18 to 0.52)
  • In patients with  BRCA1 mutation: 59% (HR, 0.41; 95% CI, 0.30 to 0.56)
  • In patients with  BRCA2 mutation: 80% (HR 0.20; 95% CI, 0.10 to 0.37)

Did this answer your question?
Additional feedback? (Optional)
Thank you for your feedback!