Management of oligometastatic ovarian cancer recurrence during PARP inhibitor maintenance

Abstract

ObjectiveThe benefit of surgery and maintenance treatment with PARP inhibitors (PARPi) has been clearly demonstrated in ovarian cancer. Also, the efficacy and safety of stereotactic body radiotherapy has been shown in patients with metastatic, persistent, and recurrent disease. The aim of this study is to evaluate the management of oligometastatic progression during PARPi maintenance treatment.MethodsThis is an observational, retrospective, single-arm study conducted from June 2017 to December 2020 in patients with recurrent ovarian cancer with oligometastatic progression under PARPi maintenance treatment and receiving surgery or stereotactic body radiotherapy for such recurrence. PARPi treatment was continued until further progression of the disease. The primary objective of the study was the median prolongation of the treatment-free interval-p (without platinum) after local treatment.ResultsA total of 186 patients with ovarian cancer were treated with PARPi at recurrence. Of these, 30 (16%) developed oligometastatic progression. The median age was 49.5 years (range 35–73). Olaparib, niraparib and rucaparib were administered to 33%, 60%, and 7% of patients, respectively. The median prolongation of the treatment-free interval-p of patients treated with surgery or stereotactic body radiotherapy was 6 and 10 months, respectively (p=0.53). The median treatment-free interval-p of patients treated with surgery or stereotactic body radiotherapy at the time of oligometastatic progression was 32 and 29 months, respectively (p=0.44). At the time of this publication, 50% of patients are still on treatment with PARPi following progression.ConclusionsPatients with recurrent ovarian cancer who have oligometastic progression during PARPi maintenance may continue to benefit from PARPi if combined with local treatment.

The first real-world study on the role of carbon ion radiotherapy for oligo-metastatic, persistent, or recurrent (MPR) ovarian/fallopian tube cancer

“…To note that currently there is no consensus about the PARP-I reduction or the optimal time to suspend PARP-I before and after RT in MPR ovarian cancers. In our clinical practice, PARP-I were stopped before the treatment and, similarly to the SBRT published data, [25] this approach seemed not to increase toxicity.…”

“…In oligometastatic settings, the achievement of high ORR has proved to be a pivotal goal of any locoregional treatment, including RT [24] , allowing in the case of ovarian cancer to raise a “drug-free holiday”, crucial in the chronicization of the disease. In this “ PARP-I era ”, all efforts should be made to avoid a rechallenge with cytotoxic platinum-based chemotherapy, considering that platinum-sensitive MPR ovarian cancers are eligible for PARP-I [25] . This issue is crucial, knowing that, in the OReO/ENGOT Ov-38 trial the maintenance with olaparib rechallenge was effective in overall progression-free survival regardless of BRCA status [26] .…”

Poly (ADP-ribose) polymerase inhibitors (PARPi) in ovarian cancer: lessons learned and future directions

“…Two retrospective studies suggested that patients with oligometastatic progression under PARPi may continue to benefit from PARPi maintenance if managed with locoregional treatment, either surgery or stereotactic body radiotherapy 4849 The rationale behind this is that locoregional treatment may remove those neoplastic clones that developed PARPi resistance while the rest of the disease remains stable under PARPi influence.…”

Oligo-Metastatic Cancers: Putative Biomarkers, Emerging Challenges and New Perspectives

“…The incidence of OMD varies depending on the type of tumors. It was hypothesized in the past that some cancers such as pancreatic adenocarcinoma and small-cell lung cancer, never present with an oligo-metastatic behavior; to date, an oligo-metastatic status has been reported in all cancers [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ]. The incidence of OMD varies greatly among cancer types, ranging from extremely rape (such as SCLC where only a few case reports are described) [ 21 ] to 10–40% of HCC [ 25 , 26 ].…”