麻豆传媒

Patients with recurrent platinum-sensitive ovarian cancer did just as well with cytoreductive surgery alone as they did with surgery plus intraperitoneal chemotherapy, according to a randomized trial.

Median progression-free survival (PFS) improved from 23 months with surgery alone to 25 months with the addition of hyperthermic intraperitoneal chemotherapy (HIPEC), a nonsignificant difference. Post-recurrence survival (PRS) at 5 years favored the HIPEC group (75.9% vs 61.6%), but that difference also did not achieve statistical significance. Postoperative adverse event (AE) rates were similar between the two groups, reported Anna Fagotti, MD, PhD, of the Catholic University of the Sacred Heart in Rome, and co-authors in the .

The "exceptionally long" PFS in both groups exceeded expectations. Two patient-selection factors might have biased the results toward the null side: an "extremely platinum-sensitive" population (median platinum-free interval [PFI] of 18 months) and attainment of complete gross resection in 95% of the patients.

"It is conceivable that these two inclusion criteria may be responsible for better PFS, even in patients without HIPEC, thus making the study planned difference in median PFS unmeasurable," the authors stated.

Additionally, 43.5% of the patients had BRCA mutations, which also suggested a more favorable-risk population.

The high rate of complete resection contrasts with results of other recent studies: SOC-1 (76.5% complete resection), DESKTOP-III (72.5%), and GOG-213 (64.0%). The resection rates were associated with a median PFS of 18-21 months, regardless of whether complete gross resection was achieved.

Primary results of the Italian trial also differed from the recently reported CHIPOR trial, which showed almost a 10-month improvement in overall survival with the addition of HIPEC to surgery, despite a modest PFS of 10.2 months versus 9.5 months with surgery alone. In an accompanying editorial, Taymaa May, MD, of Brigham and Women's Hospital in Boston, said the CHIPOR results "could signal a paradigm shift in the role of secondary cytoreductive surgery for ovarian carcinoma. As the landscape of ovarian cancer management evolves, HIPEC is poised to be an integral component of multimodal therapeutic strategies aimed at improving long-term outcomes."

Conducted at eight centers in Italy, HORSE involved 167 patients with recurrent platinum-sensitive ovarian cancer and a minimum PFI of 6 months. All patients had surgery with a goal of complete cytoreduction, defined as no visible residual disease or residual disease (<0.25 cm). They were randomized to HIPEC or placebo at the time of surgery, and all patients received adjuvant chemotherapy after surgery.

The primary endpoint was PFS, and key secondary endpoints were safety and PRS. All patients had a minimum follow-up of 24 months from cytoreductive surgery, and CT imaging of the chest, abdomen, and pelvis was performed at 1, 6, 12, 18, and 24 months. Median follow-up was 83 months.

The trial ended early (after 139 PFS events) because of a marked decrease in the event rate. The marginal difference for rejecting the null hypothesis was 10%.

The results showed a 2-month difference in PFS favoring HIPEC but with overlapping confidence intervals for surgery-alone (17-29 months) and HIPEC (18-32 months) arms. The probability of PFS at 2 years was 47.3% with surgery alone and 51.1% with the addition of HIPEC, which did not achieve statistical significance. The median PRS was 101 months with surgery and 91 months with the addition of HIPEC (P=0.40).

A total of 40 AEs occurred from randomization to 6 weeks after completion of chemotherapy and did not differ between the surgery (n=18) and HIPEC (n=22) arms. Grade 3/4 AEs occurred in 7.1% of the surgery group and 12.2% of the surgery-HIPEC group (P=0.26).

Comment