Evaluation of patterns of progression on poly (ADP-ribose) polymerase inhibitor (PARPi) maintenance in ovarian cancer: a cross-sectional study

Abstract

IntroductionDespite improvement in progression-free survival with poly (ADP-ribose) polymerase inhibitors (PARPi) as maintenance therapy for ovarian cancer, many patients will eventually progress on therapy. Oligoprogression is uniquely suited to considerations of local consolidation therapy in this setting, but not commonly used in ovarian cancer. In this study we evaluated the proportion of patients on PARPi maintenance who developed limited sites of disease, the location of progression, and their natural history.MethodsFrom January 2006 to December 2020, natural language processing software (DEEP6AI) was used to identify 58 patients with ovarian cancer treated with PARPi maintenance after complete or partial response after surgery and platinum-based chemotherapy at our institution. Patients were assessed for presence and location of recurrence based on radiologic findings.ResultsThe median patient age was 65 (IQR 57–71) years. Patients had a median of two lines of chemotherapy prior to starting PARPi. With a median follow-up of 48 (range 12–149) months, 32 (55%) patients had a recurrence on maintenance olaparib and 11 (34%) patients developed oligoprogression (≤3 sites). For the 11 patients with oligoprogression, three patients developed recurrence in one site, five in two sites, and three in three sites. The sites of oligoprogression were pelvic/periaortic nodal (27%), peritoneal (27%), liver (27%), lung/mediastinal (14%), and brain (5%). The median progression-free survival for the entire cohort was 6.0 months (95% CI 4.2 to 7.8); median overall survival was not met. There were no significant differences in overall survival (p=0.81) or progression-free survival (p=0.95) between patients with and without oligoprogression.ConclusionsOne-third of patients on PARPi maintenance experienced oligoprogression defined as limited to ≤3 sites. These patients may benefit from local consolidation therapy. A larger dataset is needed to validate these findings to assess if trials investigating local therapy for these patients is of value.

PARP Inhibitors in Brain Metastases from Epithelial Ovarian Cancer Through a Multimodal Patient Journey: Case Reports and Literature Review.

“…Compelling evidence from the updated analysis of the phase III ENGOT-OV16/NOVA trial highlights the extended benefit (primary endpoint PFS) of Niraparib monotherapy beyond first disease progression in both the gBRCA-mut and BRCA wildtype cohorts, respectively [42]. This final data supports the safe long-term use of Niraparib in the platinum-sensitive relapsed setting [41]. However, none of the prospective registration trials addressed PARPi efficacy in BM patients, albeit those with stable metastases being eligible [15].…”

“…These patients may benefit from local consolidation therapy, albeit being rarely employed in EOC. No survival differences in patients with and without oligo-progression were found [41] (as detailed in the Supplementary Table S1). Prospective validation of these findings is mandated to address the value of local therapy for these patients [41].…”

“…In detail, they report the Niraparib (cases four-six) and Olaparib (case five) continuation beyond intracranial-only relapse (oligometastases) treated with local therapy. Despite the strong prognostic impact of PARPi in platinum-sensitive recurrence, many patients will eventually progress on maintenance therapy [41]. Compelling evidence from the updated analysis of the phase III ENGOT-OV16/NOVA trial highlights the extended benefit (primary endpoint PFS) of Niraparib monotherapy beyond first disease progression in both the gBRCA-mut and BRCA wildtype cohorts, respectively [42].…”

Subsequent management and outcomes after first-line PARP inhibitors progression in ovarian cancer patients

“…Patterns of disease progression may be different in patients receiving PARPi or not. Cerda et al found one-third of patients on PARPi maintenance experienced oligoprogression defined as limited to ≤ 3 sites and these patients may benefit from local consolidation therapy [ 29 ]. Cytoreduction surgery was an effective local therapy for oligoprogression.…”

The role of inflammatory factors and T‐cell subsets in the diagnosis of recurrence in epithelial ovarian cancer patients and the effect of olaparin treatment on them

“…They mainly inhibit the repair of DNA single‐strand damage in cancer cells, resulting in the continuous accumulation of DNA single‐strand damage, resulting in DNA double‐strand breaks. In cancer cells with DNA homologous recombination defect, double‐strand breaks cannot be repaired with high fidelity, resulting in cytotoxicity and “synthetic lethal effect.” 8 A randomized study 9,10 confirmed the excellent efficacy of olaparib in second‐line maintenance therapy in platinum‐sensitive recurrent ovarian cancer patients. Subsequently, the researchers applied olaparib to the first‐line maintenance treatment of newly diagnosed ovarian cancer and achieved very encouraging research results 11 …”