Treatment with the anti-cancer agent apitolisib has helped two patients with peritoneal mesothelioma (MPeM), a British study shows.
The study, “Indolent peritoneal mesothelioma: PI3K-mTOR inhibitors as a novel therapeutic strategy,” appeared in the journal ESMO Open and was based on research led by gynecologist Susana Banerjee of London’s Royal Marsden NHS Foundation Trust.
MPeM is a rare malignancy that affects the peritoneum, a thin membrane surrounding the abdomen. MPeM is common in younger women and exhibits non-specific features, including abdominal pain, palpable pelvic masses, altered bowel habit, fever and weight loss and a wide clinical spectrum that ranges from indolent to aggressive disease.
Limited information is available on its molecular triggers, and few clinical studies have been done. Most data comes from small studies or is extrapolated from pleural mesothelioma, which occurs in the membranes surrounding the lungs. But, unlike its pleural counterpart, the evidence linking MPeM with asbestos exposure is weak.
Standard therapy consists of curative surgery, or palliative chemotherapy with Alimta (pemetrexed) in inoperable patients. Data on the use of Alimta in MPeM patients is limited to Phase 2 studies and show improved survival rates in combination with other chemotherapy agents. Tests of novel drugs have not been successful.
Doctors report that PI3K and two other molecular pathways, PTEN and AKT-mTOR, lead to formation of tumors. Therefore, stopping these pathways could benefit mesothelioma patients.
Indeed, the study describes the symptomatic and clinical benefit with apitolisib, a dual PI3K-mTOR inhibitor for subsequent relapses, in two young women with papillary MPeM, which is a non-invasive form not associated with asbestos exposure. Although papillary MPeM generally presents a excellent prognosis, the potential for aggressive progression exists. Apitolisib had shown promise in patients with mesothelioma in early phase studies.
The patients had received Alimta-based chemotherapy, followed by widespread recurrence. After apitolisib treatment, both women saw their tumors shrink. One patient exhibited a partial response for nearly three years. Both women are alive and well 10 and 13 years after diagnosis.
Current data indicate no mutations in 19 oncogenes in either patient. But, further genetic determinations are warranted, as certain mutations could account for the sensitivity to PI3K-mTOR inhibition with apitolisib.
The cases also highlight the difficulty in accurately diagnosing MPeM. “From our experience, laparoscopic biopsies were the most reliable approach to ensure the right diagnosis and specific histological subtype was confirmed which is essential to facilitate the optimal clinical management,” researchers wrote. Conversely, MRI scans are particularly useful during the follow-up period to track disease progression.
These cases belong to the indolent form of MPeM that favors long-term survival. The results warrant early phase clinical studies and highlight the potential use of PI3K-mTOR inhibitors as novel targeted therapies after palliative chemotherapy in MPeM.
“Development of prognostic biomarkers is essential to aid identify tumor aggressiveness, help stratify patients and facilitate treatment decisions,” authors added.
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