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HIPEC shows survival benefit for advanced ovarian cancer

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Questions abound for HIPEC in ovarian cancer

Although the data reported by Dr. van Driel and her colleagues represent an important first step, the findings “should not drive changes in practice yet,” according to David R. Spriggs, MD, and Oliver Zivanovick, MD.

Dr. Spriggs and Dr. Zivanovic raised questions surrounding the efficacy of adding HIPEC to surgery and suggested that the benefit observed by Dr. van Driel and her coauthors could be attributed to several variables such as the route of intraperitoneal administration or the skill level of the attending surgeon.

Currently, certain patients with advanced ovarian cancer receive primary surgery instead of neoadjuvant chemotherapy. HIPEC does not change that approach, Dr. Spriggs and Dr. Zivanovic said.

They went on to note that further “well-designed” research could reveal other patient subgroups that warrant further investigation such as those who underwent an optimal cytoreductive procedure.

“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,” they wrote.

Dr. Spriggs is the associate director for clinical and translational research at Memorial Sloan Kettering Cancer Center in New York, and Dr. Zivanovic is a gynecologic oncologic surgeon at Sloan Kettering. These remarks were taken from their invited commentary on the report by Dr. van Driel and her associates. Dr. Spriggs reported that he is employed by the New England Journal of Medicine as an associate editor. Dr. Zivanovic reported no relevant financial disclosures.

SOURCE: Spriggs DR et al. N Engl J Med. 2018 Jan 18. doi: 10.1056/NEJMe1714556.



Patients with newly diagnosed advanced-stage ovarian cancer who were referred to receive three cycles of neoadjuvant chemotherapy experienced statistically significant improved recurrence-free survival and overall survival from hyperthermic intraperitoneal chemotherapy (HIPEC) during interval cytoreductive surgery, results of a phase 3 trial showed.

After 4.7 years’ median follow-up, 89% of patients who received surgery with no HIPEC had disease recurrence or death, compared with 81% of patients treated with HIPEC (hazard ratio, 0.66; P = .003). Patients in the HIPEC cohort experienced recurrence-free survival a median of 3.5 months longer than patients who received surgery alone (10.7 months vs. 14.2 months), Willemien J. van Driel, MD, PhD, of the Netherlands Cancer Institute, Amsterdam, and her colleagues reported in the New England Journal of Medicine.

Dr. van Driel and her coauthors also reported a median 11.8 months increased overall survival (33.9 months vs. 45.7 months) for HIPEC, compared with surgery alone.

Both recurrence-free survival and overall survival remained consistently beneficial for patients in the HIPEC group across prespecified stratification factors and subgroups, including age, histology type, regional involvement, and previous surgery, according to the researchers.

They also reported that no significant differences between the two groups were noted in the incidence of adverse events of any grade. In total, grade 3 or 4 adverse events were reported by 32 patients (27%) who received HIPEC and 30 patients (25%) who received surgery (P = .76); the most common were abdominal pain, infection, and ileus.

Combination treatment with intravenous and intraperitoneal chemotherapy has been shown to prolong overall survival after primary cytoreductive surgery, according to the authors.

“Catheter-related problems, increased demands on the patient, and gastrointestinal and renal side effects have hampered the adoption of this approach in most countries,” the researchers wrote. “Hyperthermia increases the penetration of chemotherapy at the peritoneal surface and increases the sensitivity of the cancer to chemotherapy by impairing DNA repair [and] … can circumvent most of these drawbacks while maintaining its advantages.”

This research was supported by the Dutch Cancer Society. Dr. van Driel reported no relevant financial disclosures. Two other researchers reported funding from various pharmaceutical companies as well as the KFW–Dutch Cancer Foundation.

SOURCE: van Driel WJ et al. N Engl J Med. 2018 Jan 18. doi: 10.1056/NEJMoa1708618.

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