Outcomes of ovarian cancer patients treated with platinum or non-platinum based chemotherapy after PARP inhibitor maintenance.

Abstract

5563 Background: PARP inhibitors (PARPi) are approved for maintenance treatment of platinum sensitive ovarian cancers either after front-line therapy or after treatment for recurrence. Current recommendations include retreatment with platinum-based chemotherapy (PC) after progression on maintenance PARPi. There exists a theoretical concern that progression of disease (POD) on PARPi is indicative of the development of platinum resistance due to similar DNA targets of platinum chemotherapy and PARPi. Our objective was to evaluate the response to subsequent chemotherapy in patients who progressed on PARPi maintenance. Methods: All patients with ovarian, fallopian tube, or primary peritoneal cancer treated with PARPi treatment from 2017 to 2021 at two academic tertiary care centers were retrospectively identified. Patients were assessed for treatment time on PARPi, time to POD on PARPi (PFS), type of chemotherapy regimen following PARPi maintenance, and time to disease progression on subsequent therapy following PARPi (PFS2). Comparative statistical analyses were performed with appropriate two-sided statistical tests. Time to progression on chemotherapy after PARPi was calculated using the Kaplan-Meier method. Results: A total of 83 ovarian cancer patients treated with PARPi were identified, and of these, 61 (73.5%) were treated with PARPi in the maintenance setting. Among the patients treated with PARPi maintenance, 22 (36.1%) remain on treatment. 19 (31.1%) patients were started on PARPi maintenance after front-line chemotherapy. While on PARPi maintenance, 63.9% discontinued PARPi, the majority due to POD, and 26.2% due to patient intolerance of side effects. Following POD, 21/29 (72.4%) received subsequent PC and 8/29 (27.6%) received non-platinum based chemotherapy (NPC). Treatment time, PFS, and PFS2 are listed in Table. Of the patients who received PC, 14/21 (66.7%) had a PFS2 of over six months and 5/21 (23.8%) had a PFS2 of over 12 months. Of the patients who received NPC, 7/8 (87.5%) had a PFS2 of over six months and 2/8 (25.0%) had a PFS2 of over 12 months. Conclusions: Following POD on PARPi, patients responded to both PC and NPC. Time to progression on subsequent chemotherapy after treatment with PARPi does not differ significantly between PC and NPC regimens. Many patients continue to see benefit from PC after PARPi maintenance. Retreatment with PC following POD on PARPi maintenance should still be considered.[Table: see text]

Treatment patterns after poly-ADP ribose polymerase (PARP) inhibitors in epithelial ovarian cancer patients

“…Our study has demonstrated that the time to first subsequent treatment is not altered by the intent of a prior PARP inhibitor, a finding that is similar to published literature 13. Though not all post PARP inhibitor randomized trials have explored this endpoint, it is notable that there was a decrease in time to first subsequent treatment in the cohorts from SOLO1 (51.8 months) and SOLO2 (27.9 months) 2 3…”

“…In our cohort, following PARP inhibitor progression, 73% and 27.3% of patients received platinum-based and non-platinum chemotherapy, respectively. This is similar to Brann et al ’s cohort of 83 patients previously receiving a maintenance PARP inhibitor, 29 patients subsequently received chemotherapy with 21 (72.4%) and 8 (27.6%) receiving platinum and non-platinum therapy, respectively 13. Similarly, in the SOLO2/ENGOT Ov-21 cohort, 51% and 53% of patients received platinum-based chemotherapy following progression on olaparib and placebo, respectively 14…”

“…For comparison, in the SOLO2/ENGOT Ov-21 cohort, it was 7.1 and 5.6 months for those receiving platinum-based chemotherapy and non-platinum-based chemotherapy, respectively 14. In a smaller study (n=29), the progression-free survival following platinum doublet therapy was statistically longer than for non-platinum therapy, at 14.4 and 5.5 months, respectively 13…”

Management of oligometastatic ovarian cancer recurrence during PARP inhibitor maintenance

“…These values are in line with those reported in our series, while adding locoregional treatment and continuing PARP inhibition. Relative to the median treatment time with PARPi, in the study by Brann et al38 this value was 9.0 and 5.5 months for platinum and non-platinum-based chemotherapy arms. The longer median treatment time with PARPi until oligometastatic progression in our series could be due to the high percentage of patients undergoing secondary cytoreductive surgery (47%) with complete cytoreduction (86%) before starting PARPi maintenance therapy, which has been shown to improve the effectiveness of PARPi as both first-line39 and second-line treatment 22–26…”

Efficacy of PARPi monotherapy and the impact to subsequent platinum-based chemotherapy in BRCA1/2 mutant ovarian cancer patients with secondary platinum-sensitive relapse

“…After Olaparib resistance, the ORR of platinum-based chemotherapy was 40% (19/48), and the median PFS was 22 weeks, suggesting that there was still a partial response to platinum-based chemotherapy after PARPi resistance. Another study found that both platinum and non-platinum chemotherapy had a response rate after resistance of PARPi maintenance therapy, with median PFS of 7.0 and 8.5 months, respectively 22 . In our study, the PFI was significantly prolonged after PARPi monotherapy, and the median TFST of subsequent platinum-based chemotherapy after PARPi resistance was 7.5 months, consistent with patients in control group with platinum-sensitive relapse after third-line platinum-based chemotherapy.…”