Trend Towards Favorable DFS Observed With Cisplatin/Paclitaxel in HRD Advanced Ovarian Cancer

The addition of paclitaxel to cisplatin did not increase perioperative morbidity and showed a trend towards longer disease-free survival (DFS) vs cisplatin alone during hyperthermic intraperitoneal chemotherapy (HIPEC) with interval debulking surgery (IDS) in patients with advanced-stage ovarian cancer, according to data from a retrospective chart review presented at the 2025 SGO Winter Meeting.1

Patients with advanced-stage ovarian cancer achieved a median DFS of 60.4 weeks vs 83.9 weeks in the cisplatin monotherapy and cisplatin/paclitaxel groups, respectively (HR, 0.90; 95% CI, 0.45-1.80).

A trend toward a longer DFS was also shown patients with homologous recombination deficient (HRD) status who received the cisplatin/paclitaxel combination. The median DFS was 228.9 weeks vs not reached in the cisplatin monotherapy vs cisplatin/paclitaxel groups, respectively. Among patients with homologous recombination proficient (HRP) status, the median DFS was 48.7 weeks vs 60.9 weeks with cisplatin monotherapy vs cisplatin/paclitaxel, respectively.

“We found that patients treated with the combination regimen had a slightly longer DFS compared [with] those treated with cisplatin [alone], but this wasn't [statistically] significant,” said lead study author Khrystyna Levytska, MD. “Within each treatment group, there was a significant difference between patients with HRD and HRP [tumors, respectively, and patients with] HRD had a longer DFS. When examining each homologous recombination group individually—HRD or HRP—patients treated with a combination regimen had a longer DFS than those treated with cisplatin alone. But this [also] wasn't statistically significant.”

Levytska is a second-year fellow in gynecologic oncology at Cedars Sinai in Los Angeles, California.

Study Background and Design

In advanced-stage ovarian cancer, HIPEC with cisplatin at the time of IDS has been shown to improve progression-free survival (PFS) and generate a sustained overall survival (OS) benefit.1,2 Previously reported findings from a study of Korean women with advanced-stage ovarian cancer demonstrated that, at a median follow-up of 69.4 months, the median PFS was 18.8 months (IQR, 13.0-43.2) in the control group vs 19.8 months (IQR, 13.7-55.4) in the HIPEC group (P = 0.43); the median OS was 61.3 months (IQR, 34.3-not reported [NR]) in the control vs 69.5 months (IQR, 45.6-NR) in the HIPEC groups, respectively (P = .52).2

Accordingly, the current analysis sought to compare perioperative outcomes and DFS intervals with cisplatin alone vs cisplatin plus paclitaxel at the time of HIPEC with IDS and stratify DFS outcomes according to patient homologous recombination status.1

The final cohort of the study (n = 54) included patients with stage III or IV high-grade serous ovarian, fallopian tube, or peritoneal cancer who received 3 to 4C neoadjuvant chemotherapy and achieved a good response; underwent IDS/HIPEC at Cedars-Sinai between 2018 and 2023; had at least 6 months of follow-up since IDS with a cutoff of January 1, 2025; and had available germline and/or somatic testing results.

Enrolled patients were either treated with 100 mg/m2 of cisplatin at 41o C between 2018 to 2021 (n = 28) or 135 mg/m2 of paclitaxel, followed by 100 mg/m2 of cisplatin at 41o C, between 2021 to 2023 (n = 26).

Data collected in the study included demographic and surgical information, postoperative course, survival data, homologous recombination status sccording to germline or somatic testing, and treatment regimen.

Patient Characteristics and Perioperative Treatment Course

The mean age of patients in the cisplatin alone group was 65.9 years (± 8.9) vs 63.0 years (± 12.0) in the cisplatin plus paclitaxel group. Most patients were White (53.6%; 46.2%), followed by Black (3.6%; 3.8%), Hispanic or Latino (21.4%; 42.3%), or other (17.9%; 7.7%). Stage at diagnosis included stage III (92.9%; 80.7%) and stage IV (7.1%; 19.2%). The primary disease site included the ovary (71.4%; 57.7%), fallopian tube (21.4%; 15.4%); and primary peritoneum (7.1%; 26.9%). Patients displayed high grade serous (96.4%; 84.6%) and other (3.6%; 15.4%) histologies.

Regarding perioperative treatment course, the mean intraoperative time with cisplatin alone, was 376.9 minutes; with cisplatin plus paclitaxel, it was 400.4 minutes.R0 cytoreduction occurred in 85.7% vs 80.8% of patients in these respective groups. The estimated blood loss was 209.8 mL vs 292.3 mL, and the transfusion rate was 10.7% vs 7.7%, respectively.

Postoperative data obtained included days in the intensive care unit (cisplatin alone, 0.54; cisplatin/paclitaxel, 0.08; P< .05), nasogastric tube removal on postoperative day (1.39; 0), return of bowel function on postoperative day (3.04; 2.92), Clavien-Dindo (CD) grade 1 complication (82.1%; 88.5%), CD grade 2 complication (7.7%; 17.9%), emesis within the first 48 hours post-operation (28.6%; 30.8%), and readmission after 30 days (3.6%; 3.8%) vs 90 days (0%; 3.8%).

“Our results suggest that tumor genetics likely are the main drivers of response to treatment. Given the widespread use of PARP inhibitors in the HRD population, our next step is to compare outcomes in patients who had IDS without HIPEC to our patient population,” Levytska concluded.

References

1. Levytska K, Axtell AE, Han SY, et al. Homologous recombination status influences response to HIPEC at the time of interval debulking surgery for ovarian cancer. Presented at: SGO Winter Meeting; January 30-February 1, 2025; Whistler, British Columbia, Canada. Rapid Fire Abstract 2.
2. Lim MC, Chang SJ, Park B, et al. Survival after hyperthermic intraperitoneal chemotherapy and primary or interval cytoreductive surgery in ovarian cancer: a randomized clinical trial. JAMA Surg. 2022;157(5):374-383. doi:10.1001/jamasurg.2022.0143