Discussion article: do we understand the role of local treatments after oligoprogression of ovarian cancer on PARP inhibitors?

Abstract

The development of poly(ADP‐ribose) polymerase (PARP) inhibitors has been the most significant breakthrough in the treatment of advanced ovarian cancer over recent decades, with olaparib being the first drug of this class. The drug showed its efficacy at many stages of the treatment of various oncological diseases, but its maximum clinical efficacy is demonstrated in the initial treatment of BRCA-associated or HRD-positive ovarian cancer. In the phase III SOLO1 (n = 391) and PAOLA-1 (n = 806) clinical trials, treatment with olaparib reduced the relative risk of disease progression by 67% and 59%, and the risk of death by 45% and 38%, respectively. At the same time, the treatment of patients with disease progression after therapy with PARP inhibitors causes reasonable concerns in clinicians, which is associated with many aspects, primarily with the lack of individually developed approaches to the management of this category of patients. This discussion article through the example of the treatment of a particular patient allows to summarize the current data on the features of the tumour process after disease progression on PARP inhibitors and possible ways to resolve the issue of drug resistance in such patients. In the clinical case under discussion, the maintenance therapy with olaparib after combination treatment in a 50-year-old woman with metachronous multiple primary BRCA-associated malignancies (breast cancer in 2005, ovarian cancer in 2018) allowed to achieve a 2-year cancer remission, after which the oligoprogression of ovarian cancer was observed. PET-CT showed a left iliac lymph node metastasis without other progressive manifestations of the disease, after which a left laparoscopic iliac lymphadenectomy was performed, and the olaparib therapy was continued until progression or intolerable toxicity. The duration of olaparib therapy from the date when the local treatment was performed is 23 months as of this writing. The article states the detailed rationale behind choosing the non-standard management and presents the results of recent studies that support the decisions made.