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A new phase 2 study shows that patients who were treated with HIPEC and Carboplatin, did not have better progression-free or overall survival.
Although hyperthermic intraperitoneal chemotherapy (HIPEC) with carboplatin appeared to be well tolerated in patients with platinum-sensitive recurrent ovarian cancer, the regimen does not appear to be effective during secondary cytoreductive surgery, according to the results of a phase 2 study (NCT01767675) published in the Journal of Clinical Oncology.
At 24-months, 8 patients (16.3%; 1-sided 90% CI, 9.7% to 100%) in the HIPEC arm and 12 patients (24.5%; 1-sided 90% CI, 16.5% to 100%) in the standard arm were without progression or death. The median progression-free survival (PFS) was 14.3 months (95% CI, 12-16) and overall survival (OS) was 55.2 months (95% CI, 50.3-78.0) for the entire cohort.
Additionally, investigators found that patients who were randomized to receive HIPEC had a median PFS of 12.3 months vs 15.7 months in the standard arm (HR, 1.54; 95% CI, 1-2.37). In the HIPEC and standard arm, OS was 52.5 months and 59.7 months respectively (HR, 1.39; 95% CI, 0.73-2.67). In a post-hoc review, recurrences between the two groups did not demonstrate a pattern of recurrence. Additionally, investigators found that patients who had BRCA mutation, had no PFS benefit with the HIPEC regimen.
The goal of the study was to assess whether the combination of HIPEC and carboplatin could improve outcomes for patients who had recurrent ovarian cancer who were undergoing secondary cytoreduction for first recurrence of platinum-sensitive disease.
HIPEC is used to treat any cancer left after surgery by heating the chemotherapy. Investigators hoped this would make it easier to kill the cancer cells.
The open label study enrolled 99 patients who were randomized to receive secondary cytoreductive surgery followed by 5 cycles of HIPEC and 800 mg/m2 carboplatin or secondary cytoreductive surgery followed by 6 cycles of intravenous carboplatin-based therapy post-operatively. After receiving HIPEC, patients received 3000 mL of saline heated to 41°C to 43°C that circulated through the abdomen post-surgery. Carboplatin was added to the patients’ catheters perfusion system.
The study had a primary end point of portion of patients without evidence of disease progression at 24 months, and a secondary end point of 30-day postoperative morbidity, OS, pharmacokinetics, and ability to complete postoperative chemotherapy.
To enroll, patients needed to be aged 21 or older and have developed first recurrence of high grad epithelial ovarian cancer 6 to 30 months following completion of first-line platinum-based chemotherapy. Patients also needed to be eligible for secondary cytoreduction and prior treatment with chemotherapy for recurrent disease was not allowed.
Prior to study enrollment, median platinum-free interval for the entire cohort prior to enrollment was 16 months. Following enrollment, 69% of patients had platinum-free interval of 12 to 30 months. In total, 82% (n = 40) patients of the HIPEC arm had successfully underwent complete gross resection, along with 94% (n = 46) in the standard arm (P = .12). Fifty patients (51%) of patients underwent a bowel resection, although notably, significantly fewer resections took place in the HIPEC arm had. Additionally, the median operative time was significantly longer in patients who were assigned to HIPEC (474 minutes vs 292 minutes; P< .001).
At the 30-day follow-up, there were no reports of mortality. Twelve patients in the HIPEC arm and 10 in the standard arm (P= .81) experienced grade 3 or greater adverse effects (AEs). Some of the most common AEs in both the HIPEC and standard cohorts included anemia (14.3% vs 16.3%), urinary tract infection (8.2% vs 0%), and ileus (4.1% vs 2%). At the last follow-up, 82 patients had progressed, while 37 had died.
“Further studies are needed to address how to best incorporate HIPEC with optimization
of the intraoperative random assignment process to minimize surgeon bias as well as careful consideration for relevant stratification factors, such as residual disease and BRCA status,” the investigators of the study concluded.
Zivanovic O, Chi DS, Zhou Q, et al. Secondary cytoreduction and carboplatin hyperthermic intraperitoneal chemotherapy for platinum-sensitive recurrent ovarian cancer: an MSK Team ovary phase II study. Published online ahead of print, May 21, 2021. J Clin Oncol. 2021. doi:10.1200/JCO.21.00605