Author of

• 31080

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  P1.06 - Mesothelioma (ID 169)

  • Event: WCLC 2019
  • Type: Poster Viewing in the Exhibit Hall
  • Track: Mesothelioma
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall

  • 31098

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    P1.06-16 - Molecular Signature in Malignant Pleural Mesothelioma (MPM). Preliminary Data of Rames Study (ID 254)

    09:45 - 18:00  |  Author(s): francesca Zanelli
    • Abstract

    Background
    

    MPM is an uncommon cancer with limited therapeutic options and poor clinical outcomes. The relative rarity of these tumor has limited the identification of MPM-driver molecular as well as the development of specific drugs

    Method
    

    RAMES study evaluated the second-line efficacy of gemcitabine/ramucirumab treatment vs. gemcitabine/placebo.

    From December 2016 to July 2018 (end of enrolment), 164 patients (pts) were admitted to this study.

    We evaluated by NGS the mutational profile of a panel of 34 genes (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 first 87 pts (54%): hystotype was epithelioid in 70 pts (80%), biphasic in 14 pts (16%) and sarcomatoid in 3 pts (4%). Median age was 63 years (range 45-81). 70 pts were male (80%) and 17 pts were female (20%). In the present analysis, we included 55 pts in stage III (63%), 26 pts in stage IV (30%) and 6 pts whose stage was unknown. Median first-line PFS platinum/pemetrexed therapy was for 5.75 months (I.C. 95% 4.75-6.76). PFS was ≤6 months for 40 pts (49%), and 6 months for 41 pts (51%).

    Result
    

    187 functional somatic mutations were identified. Genomic alterations/patient were 1 gene in 29 pts (33%), 3 genes in 18 pts (21%) and ≥5 genes in 2 pts (2%). The most frequent somatic mutations were RDX in 35 pts (40%), MXRA5 in 20 pts (23%), BAP1 in 13 pts (15%) and ACTG 1 in 9 pts (11%). When patients were collated by stage, the most frequent mutations were: MXRA5 in 16 pts in stage III (29%), BAP1 in 5 pts in stage IV (19%) and RDX in 16 pts in stage IV (62%). The percentage of somatic mutations in patients with PFS as first-line chemotherapy for ≤6 and >6 months was 2.2 and 1.6 (p=0.032), respectively. The most frequent mutations/patient for ≤6 and >6 months PFS were: RDX in 14 pts (35%) with PFS < 6, RDX in 19 pts (46%) with PFS >6 and MXRA5 in 11 pts (27%) with PFS >6.

    Conclusion
    

    This preliminary data suggests a possible role that a genetic signature may play in distinguishing MPM with different clinical-pathological features. The results are expected to be clarified further in the second step of the study, which is ongoing.

• 30601

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  P2.01 - Advanced NSCLC (ID 159)

  • Event: WCLC 2019
  • Type: Poster Viewing in the Exhibit Hall
  • Track: Advanced NSCLC
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall

  • 30616

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    P2.01-15 - Phase II Single Arm Study of CABozantinib in Non-Small Cell Lung Cancer Patients with MET Deregulation (CABinMET) (ID 2637)

    10:15 - 18:15  |  Author(s): francesca Zanelli
    • Abstract

    Background
    

    Mesenchymal-Epithelial Transition gene (MET) amplification and exon 14 skipping mutations are established oncogenic drivers in non-small cell lung cancer (NSCLC), both occurring in about 4% of cases. In patients with MET amplified or mutated lung cancer, oral MET tyrosine kinase inhibitors (TKI) showed promising activity. The American Food and Drug Administration has recently granted crizotinib a breakthrough therapy designation for MET exon 14 mutation positive NSCLC. Cabozantinib is a novel oral inhibitor of MET and other receptor tyrosine kinases that has shown preliminary activity in MET deregulated NSCLC patients pretreated with crizotinib, although definitive data on its therapeutic role are still missing.

    Method
    

    CABinMET (NCT03911193) is a phase II, single arm, multicenter study assessing the efficacy of cabozantinib in subject with MET amplification or MET exon 14 skipping mutation pretreated or not with MET inhibitors. The primary endpoint of the trial is overall response rate. Secondary efficacy endpoints are progression free survival, overall survival and disease control rate. Main inclusion criteria include histologically/cytologically confirmed diagnosis of advanced stage NSCLC, presence of MET exon 14 skipping mutation or MET amplification (MET/CEP7 ratio ≥2.2 on FISH analysis) on archival formalin-fixed paraffin-embedded (FFPE) tumor tissue or circulating tumor DNA, measurable disease, ECOG PS 0-1, at least 1 prior line of standard therapy, adequate organ function. Patients with co-existent driver events or with symptomatic brain metastases are excluded from the trial. Cabozantinib is administered orally at 60 mg once daily until disease progression, patient refusal or unacceptable toxicity. Disease is assessed every 8 weeks. Exploratory biomarker analyses are conducted on archival FFPE tumor tissue and on blood samples collected at baseline, at the time of the first disease assessment and at progression.

    Result
    

    The study is currently running in 9 Italian centers. Recruitment started in September 2018 and 6 of the planned 25 patients have been enrolled.

    Conclusion
    

    Enrollment will be completed in 24 months.