PIPAC-MMC Shows Efficacy in Multiple Response Criteria for Peritoneal Metastases

CancerNetwork® spoke with Mustafa Raoof, MD, MS, assistant professor in the Division of Surgical Oncology in the Department of Surgery and assistant professor in the Department of Cancer Genetics and Epigenetics at City of Hope Cancer Center, about the next steps for research following the exhibition of results from a phase 1 dose-escalation trial (NCT04329494) assessing the safety and feasibility of mitomycin C pressurized intraperitoneal aerosolized chemotherapy (PIPAC-MMC) in combination with systemic chemotherapy in patients with appendiceal and colorectal carcinomatosis he presented at the Society of Surgical Oncology 2025 Annual Meeting.

Raoof began by discussing the efficacy results of the phase 1 dose-escalation trial, initially highlighting a histologic response observed in a majority of patients characterized by a tumor regression as well as up to one-third of patients exhibiting a complete histologic response. He further touched upon results from a visual assessment of cancer burden per peritoneal carcinoma index, which found that approximately 85% of patients achieved a reduction in their cancer burden.

Additional results found that a majority of patients had at least stable disease via radiographic assessment with a CT scan, with at least 1 complete response and 1 partial response observed. Furthermore, blood test results revealed a decline in the carcinoembryonic antigen biomarker in most patients and an average decline of 50% in peripheral blood tumor marker levels, suggesting that evidence of response was observed across multiple evaluation standards.

Raoof then expressed that due to the safety and early efficacy of the phase 1 trial results, future research would entail a randomized clinical trial to compare the efficacy of PIPAC-MMC plus systemic therapy vs systemic therapy alone in patients with appendiceal and colorectal carcinomatosis. He explained that the results from a randomized clinical trial would help inform whether or not a PIPAC-MMC combination regimen would confer a survival advantage over systemic therapy alone as well as inform considerations for its integration into the standard of care for peritoneal metastases.

Transcript:

[Following the phase 1 dose-escalation trial], the next step is to...look at [the secondary] efficacy signals. What we found was that patients had responded by several criteria. We looked at histologic responses on biopsy [results]. The majority of patients had tumor regression or some evidence of tumor regression on their biopsy [results]. Up to one-third of patients had a complete response on their biopsy [results] to this treatment. When we looked at the visual assessment of cancer burden, we did that by looking at the peritoneal carcinoma index. What we found was that [a] majority of patients, approximately 85%, will have a reduction in their cancer burden by that assessment.

Then we looked at radiographic assessment with a CT scan. Even though CT scans are limited in assessing disease, the majority of patients who were enrolled in the trial had stable disease, meaning there was no evidence of disease progression. It is hard to pick a response, but we did see 1 complete response and 1 partial response in this study.

Finally, we looked at the blood test [results]. We looked at carcinoembryonic antigen, which is a tumor marker in the blood, and we saw that there was a decline for a majority of patients. There was an average decline above 50% in the levels of peripheral blood tumor markers. By any standard, there was evidence of response.

Because of the safety data and the early sites of efficacy, the next step for us is to launch a randomized clinical trial. Right now, the standard therapy for patients is to get systemic therapy in this setting. What we want to do is to randomly assign patients to get this systemic therapy plus PIPAC-MCC treatment, and the control arm patients will [receive] systemic therapy [alone]. The idea is to determine which patients have a survival advantage and whether or not this therapy needs to be incorporated into the standard of care.

Reference

Raoof M. Dose escalation phase 1 trial of mitomycin C pressurized intraperitoneal aerosolized chemotherapy in combination with systemic chemotherapy for unresectable appendiceal and colorectal carcinomatosis. Presented at: Society of Surgical Oncology 2025 Annual Meeting; March 27-29, 2025; Tampa, FL.