A trial comparing two intraperitoneal (IP) chemotherapy regimens and an intravenous (IV) regimen for newly diagnosed advanced ovarian carcinoma found no differences with regard to progression-free survival between the groups. The IV and IP carboplatin regimens were better tolerated than the IP cisplatin regimen.
The new study was based on previous work that found significantly improved survival with IP cisplatin and paclitaxel compared with IV therapy. “Despite the survival benefit, less than half of eligible women treated at National Cancer Institute comprehensive cancer centers received this treatment,” wrote study authors led by Joan L. Walker, MD, of the University of Oklahoma Health Sciences Center in Oklahoma City. It has been suggested that a less toxic, less complicated to deliver, and more feasible outpatient regimen is still needed.
The new study included a total of 1,560 women with newly diagnosed advanced ovarian carcinoma, randomized to receive one of three regimens: IV paclitaxel along with IV carboplatin (IV group, 521 patients); IV paclitaxel along with IP carboplatin (IP carboplatin group, 518 patients); or IV paclitaxel along with IP cisplatin (IP cisplatin group, 521 patients). All patients received bevacizumab as well. Patients were followed for a median of 84.8 months, and the results were published in the Journal of Clinical Oncology.
In the full trial cohort, patients were a median age of 58 years; 72% had primary tumors with a high-grade serous histology, 58% had only microscopic residual disease, 93% had residual tumor of 1 cm or less, and 84% had stage III disease.
The median progression-free survival duration was 24.9 months in the IV group, 27.4 months with IP carboplatin, and 26.2 months with IP cisplatin. Compared with the IV therapy, IP carboplatin had a hazard ratio (HR) for first progression or death of 0.925 (95% CI, 0.802–1.07); for IP cisplatin, the HR was 0.977 (95% CI, 0.847–1.13).
Similar results were seen among the 1,380 patients who had stage II or III and optimally resected to 1 cm or less residual disease, with no significant differences between the therapy groups. When restricted to the 870 patients with stage II or III and no gross residual disease documented at the completion of surgery, there was again no significant difference.
The median overall survival was 75.5 months with IV therapy, compared with 78.9 months with IP carboplatin and 72.9 months with IP cisplatin. The HR for death with IP carboplatin compared with IV therapy was 0.949 (95% CI, 0.799–1.128); for IP cisplatin, the HR was 1.05 (95% CI, 0.884–1.24).
A total of 25 deaths during the study were attributed in part to toxicity (8 in the IV group, 7 in the IP carboplatin group, and 10 in the IP cisplatin group). Grade 3 or worse infections were more common in the IP groups than in the IV group (P = .008). Grade 3 or worse nausea or vomiting was more common in the IP cisplatin group, at 11.0% compared with 5.1% in the IV group and 4.7% in the IP carboplatin group (P < .005). Several other adverse effects were also worse with IP cisplatin than the other therapies, including hypertension and central nervous system ischemia.
Patient-reported outcomes were similar across the groups. However, the mean Trial Outcome Index of the Functional Assessment of Cancer Therapy-Ovary scores during chemotherapy treatment were worse with IP cisplatin than with the other regimens.
“The benefit of IP administration of chemotherapy was not evident in this large randomized clinical trial,” the authors concluded, though they noted that IP therapy may still be beneficial in certain patients.
In an accompanying “Oncology Grand Rounds” article, authors led by Sara Bouberhan, MD, of Beth Israel Deaconess Medical Center in Boston, wrote that the addition of bevacizumab or changes to the specifics of the dosing schedules could potentially explain the lack of effect seen with IP therapy. They noted that there are ongoing trials that could provide more clarity on preferred treatments.
Studies such as this “suggest that new strategies will be needed to further improve the treatment of advanced ovarian cancer,” they wrote. “Emerging, novel combinations of antiangiogenic agents, PARP inhibitors, and immune checkpoint inhibitors will be a critical next step in improving the outcomes of patients with this disease.”