HIPEC Improves Survival in Advanced Ovarian Cancer

David R. Spriggs, MD

Adding hyperthermic intraperitoneal chemotherapy (HIPEC) to interval cytoreductive surgery improved relapse-free survival (RFS) and overall survival (OS) for women with newly diagnosed stage III epithelial ovarian cancer.

In results from a multicenter, open-label, phase III trial (N = 245), women who underwent HIPEC plus surgery were less likely to experience recurrence or death (HR, 0.66; 95 CI%, 0.50-0.87; P = .003) and had a longer median RFS (14.2 vs 10.7 months) compared with women who had surgery alone.¹ The probability of RFS at 3 years was 17% (95% CI, 11-26) in the HIPEC group versus 8% (95% CI, 4-16) in patients receiving surgery alone.

The median OS was 45.7 months in the HIPEC group versus 33.9 months in the surgery-alone group. At a median follow-up of 4.7 years, 62% of patients in the surgery group had died compared with 50% of patients in the HIPEC group (HR, 0.67; 95% CI, 0.48-0.94; P = .02). The 3-year probability of OS was 62% (95% CI, 54-72) in the HIPEC arm compared with 48% (95% CI, 39-58) in the surgery-alone arm.

“The effect was consistent across the levels of prespecified stratification factors and other baseline characteristics,” wrote first author Willemien J. van Driel, MD, PhD, Netherlands Cancer Institute, and colleagues. “Intraperitoneal delivery of chemotherapy enhances drug delivery at the peritoneal surface and may improve outcomes by eliminating residual microscopic peritoneal disease more efficiently than intravenous administration of chemotherapy.”

From April 2007 to April 2016, investigators in Belgium and the Netherlands enrolled women at 8 participating medical centers. Patients who had received 3 cycles of neoadjuvant chemotherapy with AUC 5 to 6 mg/mL of carboplatin and 175 mg/m² of paclitaxel could register in the trial before surgery.

Randomization took place at the time of surgery when physicians expected to achieve complete or optimal cytoreduction, and patients were assigned to surgery alone (n = 123) or HIPEC (n = 122). The HIPEC protocol involved hyperthermic perfusion of the abdominal cavity with 100 mg/m² of cisplatin. All patients received neoadjuvant chemotherapy.

Investigators included 122 patients in the surgery arm and 118 in the HIPEC arm in the safety analysis. More than 95% of the patients in each group had at least 1 adverse event (AE) of any grade from randomization to 6 weeks after completion of the last cycle of chemotherapy. There were no significant differences in the incidence of any-grade AEs observed between the 2 groups.

Roughly one-quarter of patients in both groups experienced grade 3/4 AEs. Patients in the HIPEC arm experienced more infection (6% vs 2%) and ileus (4% vs 2%), but patients in the surgery arm were slightly more likely to report anemia (5% vs 1%).

Thirty patients in the surgery group and 29 in the HIPEC group underwent bowel resection. Women in the HIPEC arm were more likely to require colostomy or ileostomy (72% vs 43%; P = .04).

More than 90% of patients in both groups completed 3 cycles of chemotherapy. Eleven patients in the surgery group and 9 in the HIPEC group had recurrent disease but received no further therapy. One patient in the surgery group died within 30 days following surgery.

Researchers observed no significant differences between the groups in health-related quality-of-life outcomes over time.

In an accompanying editorial, David R. Spriggs, MD, and Oliver Zivanovic, MD, both with Memorial Sloan Kettering Cancer Center, called the findings “a very important first step,” but not yet practice-changing.²

“Primary cytoreductive surgery for certain patients with ovarian cancer remains the preferred approach over neoadjuvant treatment, and administration of HIPEC at the time of interval cytoreductive surgery does not change that,” they wrote. “New confirmatory clinical investigations of HIPEC are needed to clarify some of the unanswered questions before HIPEC can become a common treatment strategy. These considerations will be important for clinical trial investigators as they focus on the positive effect of HIPEC as an intervention as compared with the effects of promising new agent combinations or immunotherapy treatments.”

References

1. van Driel W, Koole SN, Sikorska K, et al. Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer. N Engl J Med. 2018; 378:230-240.
2. Spriggs DR, Zivanovic O. Ovarian cancer treatment—Are we getting warmer? N Engl J Med. 2018; 378:293-294.