JONT Journal

1.      Background

PARP (Poly(ADP) RibosePolymerase)-inhibitors have recently been introduced in the treatment of patients with recurrent platinum-sensitive ovarian cancer and a BRCA-mutation. Niraparib resulted in a significantly prolonged Progression-Free Survival (PFS) in both BRCA-wild type as well as BRCA-mutated ovarian cancer recurrence in the ENGOT-OV16/NOVA Studie [1].Similarly, olaparib revealed a significant PFS benefit inBRCA-mutated patients (Study 19[2], SOLO2-Studie). The clinical course of a patient who received successfully subsequent treatmentwith the two PARP-inhibitors is described.

2.      Case Report

A 56 years-oldpatient with hereditary ovarian cancer and a BRCA2-mutationwas diagnosed with a FIGO stage IIIc high-grade serous ovarian cancer. Initially, she received3 cycles of a platinum-based chemotherapy.After interval-debulking with no residual disease she received three additional cycles of chemotherapy plus trebananib within the TRINOVA 3 study.Due to pleural tumor progression, platinum-based chemotherapy was started again. After a partial remission to second-line chemotherapy, the patient received the PARP-inhibitor niraparib fora total of eight months within the NOVA-study. A complete remission of the pleural effusion was stated.

Due to further tumor progression, Niraparib was discontinued. The patient now received 6 cycles of carboplatin and gemcitabine. After achievement of a partial remission following third line chemotherapy, treatment with the second PARP-inhibitor olaparib was initiated.The latter agentwas administered orally at 800 mg/Tag divided in two doses. The patient is currently alive and well with no evidence of disease. Toxicity was minimal. No nausea, vomiting, or diarrhea was observed (Table-1).

3.      Conclusion

Targeted therapy with PARP-inhibitors in patients with BRCA-mutated ovarian cancerrepresents a relatively new therapeutic option.Our patient is now in complete remission 4.5 years after primary diagnosis of an advanced high-grade serous ovarian cancer deveoping its first recurrence as early as 15 months after primary diagnosis. After severalplatinum-based chemotherapies including angiogenesis inhibitors and treatment with two different PARP-inhibitors the patient is now still in remission. This case illustrated that there may exist no cross-resistance between niraparib and olaparib.

Table 1: Overview of the clinical course of disease in the 56 years-old patient with FIGO IIIc recurrent ovarian cancer.

1.       Mirza M, Monk B, Herrstedt J, Oza AM, Mahner S, et al. (2017) Niraparib Maintenance Therapy in platinum-sensitive, recurrent ovarian cancer. New Engl J Med 375: 2154-2164.

2.       Ledermann J, Harter P, Gourley C, Friedlander M, Vergote I, et al. (2016) Overall survival in patients with platinum-sensitive recurrent serous ovarian cancer receiving olaparib maintenance monotherapy: an updated analysis from a randomised, placebo-controlled, double-blind, phase 2 trial. Lancet Oncol 17: 1579-1589.