Indolent peritoneal mesothelioma: PI3K-mTOR inhibitors as a novel therapeutic strategy

Area of Science:

• Oncology
• Molecular Biology

Background:

• Peritoneal mesothelioma (MPeM) is a rare cancer with poorly understood molecular drivers and a variable clinical course.
• Current treatments for MPeM, including surgery and chemotherapy, have limitations, and targeted therapies have shown disappointing results.
• Limited data exists for MPeM, often extrapolated from pleural mesothelioma, highlighting the need for specific research.

Purpose of the Study:

• To describe the management and outcomes of two young women with recurrent papillary peritoneal mesothelioma.
• To evaluate the efficacy of apitolisib, a PI3K-mTOR inhibitor, in patients with advanced MPeM after standard chemotherapy failure.
• To highlight a potential novel therapeutic strategy for a subgroup of indolent MPeM.

Main Methods:

• Case report detailing the treatment of two patients with MPeM.
• Administration of apitolisib, a dual phosphoinositide 3-kinase-mammalian target of rapamycin (PI3K-mTOR) inhibitor, for relapsed disease post-platinum-pemetrexed chemotherapy.
• Clinical and radiological assessment of treatment response and patient survival.

Main Results:

• Both patients experienced symptomatic improvement and disease control with apitolisib.
• One patient achieved a partial response lasting nearly 3 years.
• Both patients remain alive and well 10-13 years post-diagnosis, suggesting an indolent disease course in this subgroup.

Conclusions:

• This case series suggests that certain rare MPeM subtypes exhibit indolent behavior compatible with long-term survival.
• Targeted therapy with PI3K-mTOR inhibitors represents a promising novel approach for MPeM, meriting further clinical evaluation.
• The development of prognostic biomarkers is crucial for identifying tumor aggressiveness, patient stratification, and guiding treatment decisions in MPeM.