Williams Cancer Institute

Innovative Intraperitoneal Immunotherapy Shows Promise in Recurrent Gynecological Cancers

A recent study conducted by Knisely et al focused on improving treatment outcomes for recurrent gynecological cancers with peritoneal metastases. Traditional intraperitoneal chemotherapy has demonstrated superiority over intravenous chemotherapy in treating advanced ovarian cancer. However, intravenous immunotherapy with immune checkpoint inhibitors has shown limited effectiveness in recurrent ovarian, cervical, and endometrial cancers. To address this, various immunotherapeutic treatments have been investigated, including CAR-T cells targeting specific antigens overexpressed in ovarian cancer.

In this study, patients over 18 years old with confirmed diagnoses of gynecological cancers were enrolled. These included patients with ovarian, endometrial, or cervical cancer who experienced recurrence or progression of the disease after receiving first-line treatment and at least one standard second-line treatment. Patient demographic data, such as race, were self-reported, while information on gender and socioeconomic status was not collected. Eligible patients had measurable metastatic disease in the peritoneal cavity or retroperitoneal lymph nodes according to RECIST v1.1 criteria.

The trial began with a safety phase to determine the optimal dose of intraperitoneal nivolumab before combining it with ipilimumab. The recommended phase 2 dose (RP2D) was established based on toxicity rates, with subsequent administration every 2 weeks for nivolumab and every 6 weeks for ipilimumab. A cohort expansion phase was planned to evaluate the RP2D in ovarian cancer patients, ensuring that at least 12 patients received treatment at this dose.

The results of this innovative phase 1b study revealed an objective response rate (ORR) of 18.8%, slightly higher than historical response rates to intravenous immune checkpoint inhibitors. Some patients experienced durable responses to therapy, with a median response duration of almost 15 months. The intraperitoneal route of administration was considered safe and feasible, with no dose-limiting toxicities observed.

Of particular note was the case of a patient with recurrent cervical cancer who achieved complete remission (CR) and remained off treatment for over 2 years, suggesting the potential for long-term CR induction with intraperitoneal dual immune checkpoint blockade. The study also demonstrated promising overall survival rates, with 68% of patients still alive at the 2-year mark.

Regarding safety, the rate of grade 3 or higher immune-related adverse events was lower than that reported for intravenous combination therapy, supporting the hypothesis that intraperitoneal immunotherapy may lead to fewer systemic adverse events due to lower systemic absorption.

This innovative study provides compelling evidence of the efficacy and safety of intraperitoneal immunotherapy in recurrent gynecological cancers, offering hope for improved treatment outcomes in this patient population.

Reference: Knisely et al., Phase 1b study of intraperitoneal ipilimumab and nivolumab in patients with recurrent gynecologic malignancies with peritoneal carcinomatosis, Med (2024), https://doi.org/10.1016/j.medj.2024.02.003. https://www.cell.com/med/fulltext/S2666-6340(24)00075-8?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2666634024000758%3Fshowall%3Dtrue

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