Intraperitoneal carboplatin ups PFS in ovarian cancer

Progression-free survival (PFS) is significantly longer with intraperitoneal (IP) over intravenous (IV) carboplatin, when combined with dose-dense paclitaxel, in patients with ovarian, fallopian tube, or primary peritoneal cancer, regardless of residual tumour size after initial surgery, according to the phase III iPocc* trial presented at SGO 2022.

“Traditionally, the target of intraperitoneal (IP) chemotherapy for ovarian cancer was patients with minimal residual disease after debulking surgery,” explained lead author Dr Keiichi Fujiwara from Saitama Medical University International Medical Center in Hidaka, Japan.  

To assess if IP carboplatin is superior to IV carboplatin when combined with dose-dense paclitaxel, the researchers included patients with both minimal and large size residual disease after initial surgery in the iPocc trial. [SGO 2022, LBA 3]

The phase III open-label trial involved 655 patients (median age 59 years, >90 percent Japanese) with newly diagnosed stage II-IV disease who underwent an initial laparotomy or laparoscopy with primary debulking surgery, where possible. They were randomized 1:1 to receive IP or IV carboplatin in addition to weekly dose-dense paclitaxel 80 mg/m², for six to eight cycles of chemotherapy.

Over a median follow-up of 55.7 months, the researchers found that IP carboplatin significantly improved PFS compared with IV carboplatin in the intent-to-treat (ITT) population (median, 23.5 vs 20.7 months; HR, 0.83; p=0.041).

The PFS difference between treatment  groups was even more pronounce in the modified ITT population (mITT), which included only 602 patients who were eligible after exclusion by pathology review and diagnosis (median, 22.9 vs 20.0 months; HR, 0.78; p=0.009).

The difference between treatments persisted even after 5 to 10 years, Fujiwara pointed out.

Also, the PFS benefit remained regardless of the size of residual tumour after surgery, with a greater benefit seen particularly in those with residual tumour of >2 cm.

However, these did not translate into overall survival (OS) benefit, with a median of 64.9 vs 67.0 months in the IP vs IV carboplatin in the ITT population recipients (HR, 0.95; p=0.041) and 64.9 vs 64.0 months, respectively, in the mITT population (HR, 0.91; p=0.403).

According to Fujiwara, the absence of OS difference could be due to the substantial benefit conferred by the use of new agents such as PARP inhibitors in contemporary practice. “The role of IP carboplatin-based chemotherapy in the PARP inhibitor era should be elucidated,” he said.

Nonetheless, based on the long-term PFS advantage, IP carboplatin-based chemotherapy might be a powerful tool for low-resourced countries where maintenance bevacizumab or PARP inhibitors are not available or affordable.

While survival benefit with IP has been shown over IV chemotherapy — using cisplatin-based backbone — in previous randomized trials, upfront IP chemotherapy has not been widely accepted as a standard treatment because of complexity of study design and toxicity issues, Fujiwara pointed out.

“Toxicity profile was essentially equivalent in both arms except for catheter-related toxicities,” Fujiwara reported, noting that the latter occurred in 11.8 percent of patients in the IP carboplatin arm. In addition, abdominal pain was also more common in the IP than the IV carboplatin arm (51.7 percent vs 34.7 percent).

The researchers also planned to study if there are potential biomarkers for selection of patients who are most likely to benefit from IP chemotherapy in the TRiPocc study.

*iPocc: intraperitoneal therapy for ovarian cancer with carboplatin