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PHOENIX -- Combined with dose-dense paclitaxel, intraperitoneal (IP) carboplatin bested intravenous (IV) carboplatin for progression-free survival (PFS) in patients with ovarian, fallopian tube, or primary peritoneal cancer, a randomized phase III trial found.

In the intent-to-treat (ITT) population, use of IP carboplatin resulted in a 17% reduction in the risk of disease progression or death compared with IV carboplatin (HR 0.83, 95% CI 0.69-0.99, P=0.041) over a median 55 months of follow-up, reported Keiichi Fujiwara, MD, PhD, of Saitama Medical University International Medical Center in Japan, during a late-breaking abstract session at the Society of Gynecologic Oncology annual meeting.

"And there was a big difference" among the modified ITT population (HR 0.78, 95% CI 0.65-0.94, P=0.009), Fujiwara noted.

The PFS benefit was maintained regardless of tumor size, with a greater benefit in patients with larger residual disease, he added. In the ITT population, median PFS was 23.5 months in the IP arm versus 20.7 months in the IV arm, and 22.9 months versus 20 months, respectively, in the modified ITT population.

"Note that the Kaplan-Meier curves did not come together even after 5 to 10 years," Fujiwara said. "This implies that approximately 7% more patients are surviving without progression in the IP arm compared to the IV arm."

However, there was no benefit in overall survival (OS) with IP carboplatin, with a median OS of 64.9 months versus 67 months in the IV arm in the ITT population (HR 0.95, 95% CI 0.77-1.17, P=0.041) and 64.9 months versus 64 months, respectively, in the modified ITT population (HR 0.91, 95% CI 0.73-1.13, P=0.403).

"This is probably because of the huge impact of new agents, particularly PARP inhibitors," Fujiwara said.

Commenting on the trial, session discussant Deborah Armstrong, MD, of Johns Hopkins Sidney Kimmel Comprehensive Cancer Center in Baltimore, asked whether "the gynecologic oncology community would reconsider IP therapy."

Fujiwara pointed out that while previous randomized trials have demonstrated a survival benefit with IP cisplatin-based chemotherapy compared with IV chemotherapy for optimally debulked advanced ovarian cancer, "frontline IP chemotherapy has not been widely accepted as a standard treatment due to trial design and toxicity issues."

"Moreover, IP carboplatin has never been studied in a phase III trial prior to the initiation of this study," he added.

The trial included 655 patients with stage II-IV disease from Japan, Singapore, Korea, Hong Kong, New Zealand, and the U.S. Median age was 59, and over 90% of patients were Japanese. Most patients had primary ovarian cancer.

All patients underwent an initial laparotomy or laparoscopy with primary debulking surgery, if possible, and were randomized 1:1 to receive IP or IV carboplatin with weekly dose-dense paclitaxel.

Fujiwara noted that 55% of the patients had residual tumors larger than 2 cm after the initial surgery.

The large proportion of patients with bulky suboptimal disease was the trial's most unique feature, said Armstrong, since most previous IP trials were largely limited to optimally debulked patients. These patients "clearly benefit from the treatment," she added, and thus it is "a viable option for patients with bulky disease."

Overall toxicities were similar between the two groups, with the exception of port catheter-related infections, which occurred in 30 patients in the IP arm versus two patients in the IV arm.

Fujiwara noted that more research is needed to identify biomarkers to select patients for IP therapy.

"Future trials are necessary to elucidate the true role of IP carboplatin-based chemotherapy in patients with a BRCA mutation," he said. "And based on the long-term PFS advantage, IP therapy might be a strong weapon where maintenance therapy is not available or affordable."

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