Pharmacokinetics of cisplatin during open and minimally-invasive secondary cytoreductive surgery plus HIPEC in women with platinum-sensitive recurrent ovarian cancer: a prospective study

5534 Background: NORA is the first, phase III, randomized controlled trial (RCT) that demonstrated individualized starting dose regimen of niraparib, which significantly improved PFS in Chinese patients with platinum-sensitive recurrent ovarian cancer (PSROC). This sub-group analysis evaluated the efficacy of niraparib maintenance therapy with and without secondary cytoreductive surgery (SCS) in PSROC. Methods: The NORA phase III RCT included adult (≥18 years) Chinese women with PSROC who were randomized in a 2:1 ratio to receive oral niraparib (n = 177) or matched placebo (n = 88). This retrospective subgroup analysis was based on the progression-free survival (PFS) of niraparib maintenance therapy in these two groups of patients with PSROC, patients with SCS, and patients without SCS. The PFS was assessed by blinded independent central review. The Kaplan-Meier (KM) estimator and log-rank test were performed to calculate the median PFS time. Results: Of the 265 evaluable patients, 69 (26.0%) patients received the SCS (niraparib, n = 48; placebo, n = 21), and 196 (74.0%) patients were without SCS (niraparib, n = 129; placebo, n = 67). Among patients with and without SCS, baseline characteristics for BRCA mutation were 26.1% vs 41.8%, complete response to last platinum-based chemotherapy were 68.1% vs 43.9%, time (6-12 months) to progression after penultimate therapy were 23.2% vs 34.7%, respectively. Treatment with niraparib led to a significant reduction of risk to disease progression compared with placebo in patients with SCS (Hazard ratio [95% CI]: 0.32 [0.13–0.78]; P = 0.0102) and without SCS (0.34 [0.23–0.50]; P< 0.001). Moreover, in the subgroups of patients who received SCS, niraparib maintenance therapy had a significantly longer PFS compared with placebo (Median [95% CI]: not reached [18.33 – not estimable] vs 5.75 months [3.68 – not estimable]; P = 0.0102). This trend was also similar in the subgroup of patients who did not receive SCS (Median [95% CI]: 10.28 months [7.49 – 18.37] vs 4.90 months [3.71 – 5.52]; P < 0.0001). Conclusions: The results from this retrospective sub-group analysis revealed that niraparib maintenance therapy provided significant clinical efficacy in patients with PSROC, irrespective of SCS. Clinical trial information: NCT03705156.

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Prediction Models for Complete Resection in Secondary Cytoreductive Surgery of Patients With Recurrent Ovarian Cancer

Frontiers in Oncology ◽

10.3389/fonc.2021.674637 ◽

2021 ◽

Vol 11 ◽

Author(s):

Caixia Jiang ◽

Zhengyu Li

Keyword(s):

Ovarian Cancer ◽

Cytoreductive Surgery ◽

Prediction Models ◽

Progression Free Survival ◽

Recurrent Ovarian Cancer ◽

Operative Morbidity ◽

Platinum Sensitive ◽

Secondary Cytoreductive Surgery ◽

Platinum Based Chemotherapy ◽

Ago Score

The most advanced epithelial ovarian cancer develops recurrent disease despite maximal surgical cytoreduction and adjuvant platinum-based chemotherapy. Treatment with secondary cytoreductive surgery (SCS) combined with chemotherapy or with chemotherapy alone for patients with platinum-sensitive recurrent ovarian cancer (ROC) is currently under heated discussion. Encouragingly, the results of the AGO DESKTOP III Study and the SOC1/SGOG-OV2 trial, which have been published recently, showed a striking advantage in terms of overall survival (OS) and progression-free survival (PFS) of ROC patients undergoing SCS compared to chemotherapy alone; moreover, a benefit of SCS exclusively for patients with complete gross resection (CGR) was particularly highlighted. CGR is considered the ultimate goal of SCS, on condition that the balance between maximal survival gain and minimal operative morbidity is maintained. Several models have been proposed to predict the rate of CGR, such as the MSK criteria, the AGO score, and the Tian model, over the last 15 years. This summary is mainly about the several previously published prediction models for CGR in SCS of ROC patients and discusses the effectiveness and limitations of these prediction models.

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Secondary Cytoreduction and Carboplatin Hyperthermic Intraperitoneal Chemotherapy for Platinum-Sensitive Recurrent Ovarian Cancer: An MSK Team Ovary Phase II Study

Journal of Clinical Oncology ◽

10.1200/jco.21.00605 ◽

2021 ◽

pp. JCO.21.00605

Author(s):

Oliver Zivanovic ◽

Dennis S. Chi ◽

Qin Zhou ◽

Alexia Iasonos ◽

Jason A. Konner ◽

...

Keyword(s):

Ovarian Cancer ◽

Phase Ii ◽

Intraperitoneal Chemotherapy ◽

Cytoreductive Surgery ◽

Hyperthermic Intraperitoneal Chemotherapy ◽

Phase Ii Study ◽

Recurrent Ovarian Cancer ◽

Hazard Ratio ◽

Platinum Sensitive ◽

Secondary Cytoreductive Surgery

PURPOSE The purpose of this phase II study was to evaluate hyperthermic intraperitoneal chemotherapy (HIPEC) with carboplatin for recurrent ovarian cancer during secondary cytoreductive surgery. MATERIALS AND METHODS Patients were intraoperatively randomly assigned to carboplatin HIPEC (800 mg/m2 for 90 minutes) or no HIPEC, followed by five or six cycles of postoperative IV carboplatin-based chemotherapy, respectively. Based on a binomial single-stage pick-the-winner design, an arm was considered winner if ≥ 17 of 49 patients were without disease progression at 24 months post-surgery. Secondary objectives included postoperative toxicity and HIPEC pharmacokinetics. RESULTS Of 98 patients, 49 (50%) received HIPEC. Complete gross resection was achieved in 82% of the HIPEC patients and 94% of the standard-arm patients. Bowel resection was performed in 37% of patients in the HIPEC arm compared with 65% in the standard ( P = .008). There was no perioperative mortality and no difference in use of ostomies, length of stay, or postoperative toxicity. At 24 months, eight patients (16.3%; 1-sided 90% CI, 9.7 to 100) were without progression or death in the HIPEC arm and 12 (24.5%; 1-sided 90% CI, 16.5 to 100) in the standard arm. With a medium follow-up of 39.5 months, 82 patients progressed and 37 died. The median progression-free survival in the HIPEC and standard arms were 12.3 and 15.7 months, respectively (hazard ratio, 1.54; 95% CI, 1 to 2.37; P = .05). There was no significant difference in median overall survival (52.5 v 59.7 months, respectively; hazard ratio, 1.39; 95% CI, 0.73 to 2.67; P = .31). These analyses were exploratory. CONCLUSION HIPEC with carboplatin was well tolerated but did not result in superior clinical outcomes. This study does not support the use of HIPEC with carboplatin during secondary cytoreductive surgery for platinum-sensitive recurrent ovarian cancer.

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