PARP inhibitor monotherapy prolonged disease control in a case of recurrent epithelial ovarian cancer without BRCA mutation
History, presentation and management
This patient presented to the clinic at the second recurrence of the disease with extensive spread of cancer within the abdomen. Since her disease progressed 10 months after the last course of platinum-based chemotherapy, she was still considered platinum-sensitive.1,2 She received cytoreductive surgery and hyperthermic intraperitoneal chemotherapy, and in accordance with the European Society for Medical Oncology (ESMO)-European Society of Gynaecological Oncology (ESGO) recommendations,1 she was given third-line platinum-based chemotherapy. Because the patient responded well to the platinum rechallenge, olaparib maintenance therapy was chosen.1 (Figure)
Olaparib is a poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor indicated for maintenance treatment in patients with recurrent epithelial ovarian cancer who are in complete or partial response to platinum-based chemotherapy.3* In the phase III SOLO2 study in 295 patients with a BRCA1/2 mutation, investigator-assessed median progression-free survival (PFS) was significantly longer with olaparib tablet 300 mg BID than placebo (19.1 months vs 5.5 months; hazard ratio [HR], 0.30; 95 percent confidence interval [CI], 0.22 to 0.41; p<0.0001).4
While evidence suggests that PARP inhibitors provide the greatest benefits in patients with BRCA mutation,1 olaparib has demonstrated survival benefits in those without the mutation as well.5 The phase II study 19 included 265 patients with platinum-sensitive, relapsed, high-grade serous ovarian cancer with or without BRCA1/2 germline mutations.5 Median PFS was significantly longer in those receiving olaparib capsule 400 mg BID than those receiving placebo (8.4 months vs 4.8 months; HR, 0.35; 95 percent CI, 0.25 to 0.49; p<0.001).5 Subgroup analyses also favoured olaparib regardless of BRCA status (with mutation: HR, 0.18; 95 percent CI, 0.10 to 0.31; p<0.0001) (without mutation: HR, 0.54; 95 percent CI, 0.34 to 0.85; p=0.0075).5,6
Olaparib was well tolerated in both SOLO2 and study 19.4,5 Fewer than 50 percent of patients receiving olaparib required dose interruption or reduction due to adverse events (AEs); the most common grade 3 AEs were anaemia, fatigue and neutropenia.4,5 Olaparib is now available in tablet form, which offers a reduced pill burden compared with the original 50 mg capsule formulation.7 It should be mentioned that the two formulations are not bioequivalent and the doses are not interchangeable: expert opinions suggest that 400 mg capsules BID may be switched to 300 mg tablet BID; and 200 mg capsules BID to 250 mg tablet BID.3,7
The present case echoes the findings from the clinical trials in that olaparib maintenance therapy prolongs disease control in a patient with recurrent epithelial ovarian cancer. The fact that the patient has no BRCA mutation was particularly encouraging, highlighting the utility of olaparib irrespective of BRCA status. Most importantly, the patient remained well after 12 months of treatment and was able to maintain a high-quality, active lifestyle.