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

Our plain-English summary of Indolent peritoneal mesothelioma: PI3K-mTOR inhibitors as a novel therapeutic strategy, by S.O. Dolly, C. Migali, N. Tunariu, et al (ESMO Open, 2017).

The study

• Authors: S.O. Dolly, C. Migali, N. Tunariu, C. Della-Pepa, S. Khakoo, S. Hazell, J.S. de Bono, S.B. Kaye, S. Banerjee
• Journal: ESMO Open
• Published: 2017;2(1):e000101
• Cited by: 8 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Unlabelled: Peritoneal mesothelioma (MPeM) is a scarce abdominal-pelvic malignancy that presents with non-specific features and exhibits a wide clinical spectrum from indolent to aggressive disease. Due to it being a rare entity, there is a lack of understanding of its molecular drivers. Most treatment data are from limited small studies or extrapolated from pleural mesothelioma. Standard treatment includes curative surgery or pemetrexed-platinum palliative chemotherapy. To date, the use of novel targeted agents has been disappointing. Described is the management of two young women with papillary peritoneal mesothelioma with widespread recurrence having received platinum-pemetrexed chemotherapy. Both patients obtained symptomatic and disease benefit with apitolisib, a dual phosphoinositide 3-kinase-mammalian target of rapamycin (PI3K-mTOR) inhibitor for subsequent relapses, with one patient having a partial response for almost 3 years. Both are alive and well 10-13 years from diagnosis.

Conclusion: These case presentations highlight a subgroup of rare MPeM that behave indolently that is compatible with long-term survival. This series identifies the use of targeted therapies with PI3K-mTOR-based inhibitors as a novel approach, warranting further clinical assessment. Development of prognostic biomarkers is essential to aid identify tumour aggressiveness, help stratify patients and facilitate treatment decisions.

In plain English

This article reported two cases: women aged 28 and 19 treated for peritoneal mesothelioma at the Royal Marsden Hospital, London. Final histology was papillary peritoneal mesothelioma in the first patient and well-differentiated papillary mesothelioma (WDPM) in the second. The article did not describe asbestos exposure for either patient. Both had repeated platinum-pemetrexed chemotherapy, which led to disease stability, before further relapses. Each then received apitolisib, a drug that blocks the PI3K-mTOR pathway, in an early-phase trial. In the first patient, the tumour marker CA-125 fell from 217 to 32, scans confirmed a partial response, and slow progression began after 2.8 years. The second received the drug for 15 months. Her tumours shrank 27% by standard criteria (stable disease overall), and MRI showed a 39% fall in tumour volume after 10 months. Neither tumour showed PIK3CA mutations or PTEN loss. The patients were alive 13 and 10 years after diagnosis. The authors concluded that some peritoneal mesotheliomas behave indolently and that PI3K-mTOR inhibitors warrant further clinical evaluation. A report of two patients cannot show how often such responses occur.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Case report of two patients (case series)
• Who was studied: Two female patients, aged 28 and 19 at presentation, treated at the Royal Marsden Hospital, London, UK
• Exposure: Asbestos exposure is not reported for either patient. The exposure studied was treatment: platinum-pemetrexed chemotherapy and then apitolisib, an experimental PI3K-mTOR inhibitor, given in early-phase trials.
• Main results:
  • In both patients, platinum-pemetrexed chemotherapy led to disease stability.
  • Case 1 (aged 28, papillary peritoneal mesothelioma): on apitolisib, CA-125 fell from 217 to 32 and a confirmed partial response was seen on scans.
  • Case 1: slow progression began after 2.8 years on apitolisib.
  • Case 2 (aged 19, WDPM): she received apitolisib for 15 months, with a 27% tumour decrease that counted as stable disease overall by RECIST criteria.
  • Case 2: MRI volume measurement showed a 39% reduction in tumour volume after 10 months of apitolisib.
  • Molecular testing of both patients found no PIK3CA or RAS/RAF mutations and no PTEN loss.
  • Case 1 was alive 13 years after diagnosis.
  • Case 2 was alive 10 years after initial presentation.
• The authors' conclusion: The authors concluded that apitolisib gave symptomatic benefit and sustained tumour shrinkage in these patients, and that this approach warrants further clinical evaluation in this rare disease.
• Limitations the authors state:
  • The authors did not test for NF2 changes, which they say could explain sensitivity to PI3K-mTOR blockade.
  • CA-125 levels fluctuated without matching scan changes, so the authors say its reliability as a marker in indolent disease is undetermined.
  • The authors say RECIST criteria may not be the best tool for measuring this diffuse disease.

Topics

Medical terms in this study, explained in our Lexicon: Peritoneal Mesothelioma, Pleural Mesothelioma, Pemetrexed (Alimta), Palliative Care, Chemotherapy, Platinum-Pemetrexed, Biomarker.

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