Gender differences in molecular-guided therapy recommendations for metastatic malignant mesothelioma

Our plain-English summary of Gender differences in molecular-guided therapy recommendations for metastatic malignant mesothelioma, by H. Taghizadeh, S. Zöchbauer-Müller, R.M. Mader, et al (Thoracic Cancer, 2020).

The study

• Authors: H. Taghizadeh, S. Zöchbauer-Müller, R.M. Mader, L. Müllauer, T. Klikovits, T. Bachleitner-Hofmann, M.A. Hoda, G.W. Prager
• Journal: Thoracic Cancer
• Published: 2020;11(7):1979-1988
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Malignant mesothelioma is an aggressive cancer and has a poor prognosis. Here, we analyzed the feasibility, molecular and gender aspects of targeted therapy recommendations for malignant mesothelioma based on the individual molecular tumor profile.

Methods: In this single-center, real-world retrospective analysis of our platform for precision medicine, we evaluated the molecular profiling of malignant mesothelioma in 14 patients, including nine men and five women. Tumor samples of the patients were examined with a 50 gene next-generation sequencing (NGS) panel, immunohistochemistry, and fluorescence in situ hybridization, to detect possible molecular aberrations which may be targeted by off-label therapy custom-tailored to the individual patient.

Results: In total, we identified 11 mutations in six of the 14 patients, including BAP1, FANCA, NF1, NF2, PD-L1, RAD52D, SETD2, SRC, and TP53. No mutation was detected in eight of the 14 patients. Targeted therapy was recommended for 11 out of the 14 patients. All recommendations were mainly based on the molecular characteristics determined by immunohistochemistry. Targeted therapy recommendations were significantly more often for men than women due to gender-specific differences in PDGFRα expression. Eventually, four patients received the targeted therapy, of whom one patient subsequently achieved stable disease.

Conclusions: Our observations suggest that a molecular-guided treatment approach is feasible for the management of advanced malignant mesothelioma. Our analysis revealed gender specific differences in PDGFRα expression that should be further evaluated in clinical trials.

© 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

In plain English

This was a small retrospective, exploratory study from a precision-medicine program in Vienna, Austria. The authors examined tumor samples from 14 patients (nine men, five women), included between June 2013 and January 2019, with stage IV malignant mesothelioma no longer responding to standard treatment. Eleven had pleural and three had peritoneal mesothelioma. Tumors were tested for gene mutations and protein markers. Asbestos exposure was not studied. They found 11 mutations in six patients and none in eight. PDGFRα, a protein, was found more often in men's tumors: 6 of 9 men versus 0 of 5 women (P = 0.016). A targeted drug was suggested for 11 of the 14 patients (79%). Three multitargeted drugs (sunitinib, dasatinib, nintedanib) were suggested only for men. Four patients received a suggested drug. Three of them died from disease progression before it could be re-checked. One man with peritoneal mesothelioma had stable disease for three months. The authors concluded that the approach is feasible but its benefit was limited, and that the PDGFRα sex difference should be studied in clinical trials. They noted the small sample size.

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: Retrospective, exploratory, single-center cohort analysis (a subgroup analysis of a precision-medicine platform, not a clinical trial)
• Who was studied: 14 Caucasian patients (9 men, 5 women) with stage IV, therapy-refractory malignant mesothelioma (11 pleural, 3 peritoneal; 13 epithelioid, 1 biphasic), profiled in the MONDTI platform at the Medical University of Vienna, Austria, from June 2013 to January 2019
• Exposure: Asbestos exposure was not studied. The study examined tumor tissue using a 50-gene sequencing panel (expanded to a 161-gene panel by mid-2018), immunohistochemistry and fluorescence in situ hybridization.
• Main results:
  • 11 mutations were found in 6 of the 14 patients. No mutation was detected in the other 8.
  • PDGFRα expression was found significantly more often in men than in women: 6 of 9 men versus 0 of 5 women (P = 0.016, Chi-squared test).
  • A targeted therapy was suggested for 11 of the 14 patients (79%).
  • The multitargeted tyrosine kinase inhibitors sunitinib (2 patients), dasatinib and nintedanib were recommended only for male patients.
  • 4 of the 11 patients (36%) received the targeted therapy. Three of them died from disease progression before restaging.
  • One male patient with peritoneal mesothelioma, treated with nintedanib, had stable disease for three months. He tolerated the drug well, with only grade I fatigue.
• The authors' conclusion: The authors concluded that precision medicine is feasible in clinical routine, that the sex-specific differences in PDGFRα expression should be further evaluated in clinical trials, and that the clinical benefit for these therapy-refractory patients was limited.
• Limitations the authors state:
  • The sample size was small, and the patients all had good performance status (ECOG 0 or 1).
  • Only one patient had a clinical benefit. The authors suggested that the time needed to obtain results (turnaround time) may be one reason.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma, Peritoneal mesothelioma.

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Prognosis, Targeted Therapy, Molecular Profiling, Next-Generation Sequencing (NGS), Immunohistochemistry, Fluorescence In Situ Hybridization (FISH), BAP1.

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