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Proffered Paper 2 – Non-metastatic NSCLC and other thoracic malignancies (mesothelioma and thymic carcinoma)

3080 - Mutational profile of malignant pleural mesothelioma (MPM) in the phase II RAMES Study

Date

30 Sep 2019

Session

Proffered Paper 2 – Non-metastatic NSCLC and other thoracic malignancies (mesothelioma and thymic carcinoma)

Presenters

Maria Pagano

Citation

Annals of Oncology (2019) 30 (suppl_5): v747-v755. 10.1093/annonc/mdz266

Authors

M. Pagano1, R. Gnoni1, C. Bonelli1, F. Zanelli1, M.C. Garassino2, G.L. Ceresoli3, G. Pasello4, M. Tiseo5, H.J. Soto Parra6, F. Grosso7, P.A. Zucali8, M. Larocca1, F. Torricelli9, A. Ciarrocchi9, C. Pinto1

Author affiliations

  • 1 Medical Oncology Unit, Clinical Cancer Centre, AUSL-IRCCS, Reggio Emilia, 42100 - Reggio Emilia/IT
  • 2 Thoracic Unit, Fondazione IRCCS - Istituto Nazionale dei Tumori, 20133 - Milan/IT
  • 3 Oncology, Humanitas Gavazzeni, 24125 - Bergamo/IT
  • 4 Oncoloy Unit, Istituto Oncologico Veneto IRCCS, 35128 - Padova/IT
  • 5 Medical Oncology, AOU di Parma, 43126 - Parma/IT
  • 6 Medical Oncology, Azienda Policlinico Università di Catania, 95037 - Catania/IT
  • 7 Oncology Dept., Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo, 15121 - Alessandria/IT
  • 8 Oncology, Istituto Clinico Humanitas, 20089 - Rozzano/IT
  • 9 Laboratory Of Translational Research, AUSL - IRCCS di Reggio Emilia, 42100 - Reggio Emilia/IT
More

Resources

Abstract 3080

Background

MPM is an aggressive cancer with poor prognosis. Platinum/pemetrexed regimen is the standard 1°-line chemotherapy (CHT) in advanced disease.

Methods

The RAMES Study evaluated the 2°-line efficacy of gemcitabine/ramucirumab treatment vs. gemcitabine/placebo. From December 2016 to July 2018 (end of enrolment), 164 pts were admitted to this study. We evaluated by NGS the mutational profile of a panel of 34 genes (gs) (ACTB, ACTG1, ACTG2, ACTR1A, BAP1, CDH8, CDK4, CDKN2A, CDKN2B, COL3A1, COL5A2, CUL1, DHFR, GOT1, KDR, KIT, MXRA5, NF2, NFRKB, NKX6-2, NOD2, PCBD2, PDZK1IP1, PIK3CA, PIK3CB, PSMD13, RAPGEF6, RDX, SETDB1, TAOK1, TP53, TXNRD1, UQCRC1, XRCC6). We reported the results of the 103 pts (63%) of both arms with specimen available for molecular analysis. Median age was 63 years (45-81), 24.3% (n = 25) were females and 75.7% (n = 78) males. Histotype was 83.5% (n = 86) epithelioid and 16.5% (n = 17) non-epithelioid. 37.8% (n = 39) were stage IV, 60.2% (n = 62) were stage III, and 1.9% (n = 2) were unknown. In 1°-line platinum/pemetrexed CHT treated pts, the median PFS was 5.75 months (ms) (C.I. 95% 4.75-6.76). 50 pts had PFS <6 ms, while 50 pts had PFS >6 ms (n = 3 not available).

Results

260 functional somatic mutations were identified in 28 of the 34 gs analyzed. 75pts (72.8%) displayed mutations in 1 to 3 gs while 17 pts (16.5%) showed mutations in at least 4 gs. No mutated gs were detected for 11 pts (10.7%). The number of mutated gs was positively associated with higher stage and metastatic behavior (p = 0.025) and increased 1°-line PFS (p = 0.011). RDX (42.7%), MXRA5 (23.3%), BAP1 (13.6%), PIK3CB (10.7%) and NF2 (10.7%) were the most frequently mutated gs in our pts. Mutations in RAPGEF6 (p = 0.013) and ACTG1 (p = 0.01) were associated with non-epithelioid, while mutations in BAP1 (p = 0.041) were associated with PFS >6 months. A positive trend of association was also observed between mutations in COL3A1 (p = 0.052) and NFRKB (p = 0.052) and stage IV.

Conclusions

In MPM the identification of molecular gene alterations could be an important starting point for understanding the main pathways involved in prognosis and sensitivity/resistance to therapy. In the RAMES Study, the mutation of gene BAP1 is related to a prolonged PFS at the 1°-line CHT (p = 0.041).

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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