Cytoreductive surgery followed by chemotherapy and olaparib maintenance in BRCA 1/2 mutated recurrent ovarian cancer: a retrospective MITO group study

Abstract

IntroductionThe role of cytoreductive surgery in the poly-ADP ribose polymerase inhibitors era is not fully investigated. We evaluated the impact of surgery performed prior to platinum-based chemotherapy followed by olaparib maintenance in platinum-sensitive BRCA-mutated recurrent ovarian cancer.MethodsThis retrospective study included platinum-sensitive recurrent ovarian cancer BRCA-mutated patients from 13 Multicenter Italian Trials in Ovarian cancer and gynecological malignancies centers treated between September 2015 and May 2019. The primary outcomes were progression-free survival and overall survival. Data on post-progression treatment was also assessed.ResultsAmong 209 patients, 72 patients (34.5%) underwent cytoreductive surgery followed by platinum-based chemotherapy and olaparib maintenance, while 137 patients (65.5%) underwent chemotherapy treatment alone. After a median follow-up of 37.3 months (95% CI: 33.4 to 40.8), median progression-free survival in the surgery group was not reached, compared with 11 months in patients receiving chemotherapy alone (P<0.001). Median overall survival was nearly double in patients undergoing surgery before chemotherapy (55 vs 28 months, P<0.001). Post-progression therapy was assessed in 127 patients: response rate to chemotherapy was 29.2%, 8.8%, and 9.0% in patients with platinum-free interval >12 months, between 6 and 12 months, and <6 months, respectively.ConclusionCytoreductive surgery performed before platinum therapy and olaparib maintenance was associated with longer progression-free survival and overall survival in BRCA-mutated platinum-sensitive relapsed ovarian cancer patients. In accordance with our preliminary results, the response rate to chemotherapy given after progression during olaparib was associated with platinum-free interval.

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

“…The logical question is whether the introduction of PARPi in the first-line setting would mitigate the role of secondary cytoreductive surgery or, on the contrary, further reinforce it. A retrospective MITO group study confirmed the positive role of secondary cytoreductive surgery before platinum therapy and olaparib maintenance in BRCAm patients 58. In this study, the PARPi was used in a relapsed setting rather than in the first line and so there are still some issues on surgery secondary to PARPi.…”

“…A retrospective MITO group study confirmed the positive role of secondary cytoreductive surgery before platinum therapy and olaparib maintenance in BRCAm patients. 58 In this study, the PARPi was used in a relapsed setting rather than in the first line and so there are still some issues on surgery secondary to PARPi. Nevertheless, the pattern of first recurrence under or after PARPi is frequently oligometastatic 59 and secondary cytoreductive surgery might play even a greater role in the post-PARPi era.…”

The value of PET/CT for cytoreductive surgery selection in recurrent ovarian carcinoma

“…Two issues were not addressed. Regarding the prognostic value of BRCA or homologous recombination deficiency status in the recurrent setting for selection for surgery, a recent retrospective MITO group study suggested that BRCA-mutated patients who were undergoing SCS followed by chemotherapy and maintenance with a PARP inhibitor had a better DFS and OS compared with those who did not receive surgery [ 23 ]. Moreover, our previous data have suggested a potential benefit of SCS for DFS compared with only chemotherapy, irrespective of BRCA status, in patients who are primarily not treated with a PARP inhibitor.…”

Olaparib beyond progression compared with platinum chemotherapy after secondary cytoreductive surgery in patients with recurrent ovarian cancer: phase III randomized, open-label MITO 35b study, a project of the MITO-MANGO groups

“…Exploratory data from the MITO real-life experience have shown that patients with BRCA 1/2 in progression while on olaparib maintenance had a low response rate when re-exposed to a platinum-based therapy with an objective response rate of only 29.2% in patients with a platinum-free interval of more than 12 months 13. Other data from a retrospective Australian multicohort study found an objective response rate of 24.7% in 77 patients receiving chemotherapy after poly (ADP-ribose) polymerase inhibitors 14.…”