PracticeUpdate Oncology Best of 2018

EDITOR’S PICKS 14

Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer The New England Journal of Medicine Take-home message • This was a multicenter, open-label, phase III trial that randomly assigned 245 patients with stage III epithelial ovarian cancer, who had at least stable disease after three cycles of carboplatin and paclitaxel, to undergo interval cytoreductive surgery either with or without administration of HIPEC with cisplatin. Three additional cycles of carboplatin and paclitaxel were administered postoperatively. In the intention-to-treat analysis, events of disease recurrence or death occurred in 110 of the 123 patients (89%) who underwent cytoreductive surgery without HIPEC (surgery group) and in 99 of the 122 patients (81%) who underwent cytoreductive surgery with HIPEC (surgery+HIPEC group). The hazard ratio for disease recurrence or death was 0.66 (P = .003). The median recurrence-free survival was 10.7 months in the surgery group and 14.2 months in the surgery+HIPEC group. At a median follow-up of 4.7 years, 76 patients (62%) in the surgery group and 61 patients (50%) in the surgery+HIPEC group had died (HR, 0.67; P = .02). The median overall survival was 33.9 months in the surgery group and 45.7 months in the surgery+HIPEC group. • Among patients with stage III epithelial ovarian cancer, the addition of HIPEC to interval cytoreductive surgery resulted in longer recurrence-free survival and overall survival than surgery alone and did not cause higher rates of side effects. Jeffrey Wiisanen MD

paclitaxel were administered postoperatively. The primary end point was recurrence-free sur- vival. Overall survival and the side-effect profile were key secondary end points. RESULTS In the intention-to-treat analysis, events of disease recurrence or death occurred in 110 of the 123 patients (89%) who underwent cytoreductive surgery without HIPEC (surgery group) and in 99 of the 122 patients (81%) who underwent cytoreductive surgery with HIPEC (surgery-plus-HIPEC group) (hazard ratio for dis- ease recurrence or death, 0.66; 95% confidence interval [CI], 0.50 to 0.87; P=0.003). The median recurrence-free survival was 10.7 months in the surgery group and 14.2 months in the surgery- plus-HIPEC group. At a median follow-up of 4.7 years, 76 patients (62%) in the surgery group and 61 patients (50%) in the surgery-plus-HIPEC group had died (hazard ratio, 0.67; 95% CI, 0.48 Postoperatively, three cycles of carbo- platin and paclitaxel were administered. The addition of HIPEC resulted in longer recurrence-free survival (14.2 months vs 10.7 months) and median overall survival (45.7 vs 33.9 months) compared with sur- gery alone. At a median follow-up of 4.7 years, 50% in the surgery + HIPEC group and 62% in the surgery group had died COMMENT By Annette Hasenburg Prof. Dr. med I n a multicenter phase III trial, 245 patients with stage III epithelial ovarian cancer received neoadjuvant chemo- therapy with three cycles of carboplatin. Patients who had at least stable disease underwent interval cytoreductive sur- gery randomly assigned to surgery with or without hyperthermic intraperitoneal chemotherapy (HIPEC).

to 0.94; P=0.02). The median overall survival was 33.9 months in the surgery group and 45.7 months in the surgery-plus-HIPEC group. The percentage of patients who had adverse events of grade 3 or 4 was similar in the two groups (25% in the surgery group and 27% in the sur- gery-plus-HIPEC group, P=0.76). CONCLUSIONS Among patients with stage III epi- thelial ovarian cancer, the addition of HIPEC to interval cytoreductive surgery resulted in longer recurrence-free survival and overall survival than surgery alone and did not result in higher rates of side effects. Hyperthermic Intraperitoneal Chemother- apy in Ovarian Cancer. N Engl J Med 2018 Jan 18;378(3)230-240, WJ van Driel, SN Koole, K Sikorska, et al. www.practiceupdate.com/c/63235 However, some questions remain. How were patients selected for neoadju- vant chemotherapy? Upfront optimally debulked patients with advanced-stage disease (eg, in the LION study) had much longer median progression-free survival of 25.5 months and overall survival of 67.2 months than patients in this trial. Could the benefit be due to the early intraoperative administration of chemo- therapy or the dose effect of cisplatin? This trial may be an important step, but the approach is not convincing for imple- mentation in routine care yet. (HR, 0.67; 95% CI, 0.48–0.94; P = .02). The percentage of side effects of grade 3 and 4 was similar in both groups.

Abstract BACKGROUND Treatment of newly diagnosed advanced-stage ovarian cancer typically involves cytoreductive surgery and systemic chemotherapy. We conducted a trial to inves- tigate whether the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to interval cytoreductive surgery would improve outcomes among patients who were receiving neoadju- vant chemotherapy for stage III epithelial ovarian cancer. METHODS In a multicenter, open-label, phase 3 trial, we randomly assigned 245 patients who had at least stable disease after three cycles of carboplatin (area under the curve of 5 to 6 mg per milliliter per minute) and paclitaxel (175 mg per square meter of body-surface area) to undergo interval cytoreductive surgery either with or without administration of HIPEC with cisplatin (100 mg per square meter). Random- ization was performed at the time of surgery in cases in which surgery that would result in no visible disease (complete cytoreduction) or surgery after which one or more residual tum- ors measuring 10 mm or less in diameter remain (optimal cytoreduction) was deemed to be fea- sible. Three additional cycles of carboplatin and

PRACTICEUPDATE ONCOLOGY