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Helene Doubre



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    MA03 - Clinomics and Genomics (ID 119)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Advanced NSCLC
    • Presentations: 1
    • Now Available
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      MA03.09 - Dramatic Responses to Immune Checkpoint Inhibitors in MET Exon 14 Skipping Mutation (METex14mut) Non Small Cell Lung Cancers (Now Available) (ID 1621)

      10:30 - 12:00  |  Author(s): Helene Doubre

      • Abstract
      • Presentation
      • Slides

      Background

      METex14 mutations occur in 2-3% of Non-Small-Cell Lung Cancers (NSCLC), with a higher prevalence in patients aged over 70-years-old, non-smokers.and women. Crizotinib, a MET-inhibitor, allows remarkable, but often short, tumor responses. Immune Checkpoint Inhibitors (ICIs) have become pivotal treatments in NSCLC but seem less efficient in non-smokers and in case of oncogenic addiction. We report durable strong responses in four non-smoker women (A, B, C, D) and two smokers (E, F) treated by ICIs in a second-line setting for NSCLC harboring METex14 mut.

      Method

      We studied the clinical and biological characteristics and the tumor response after ICIs for each patient. The complete DNA sequencing of the tumor was available after the beginning of ICIs (explaining why crizotinib was not proposed in second line). PDL1 expression on tumor cells was evaluated by antibody clone E1L3N (Cell signaling Technology).

      Result

      Table 1 summarizes patient and tumor characteristics, and the evolution during ICIs : Nivolumab for all patients except E (pembrolizumab). There were neither EGFR, BRAF, KRAS mutations, nor ALK or ROS translocations (except minority KRAS mutation for C). No concurrent MET amplification was found.

      tableau.jpeg

      Partial or complete response was rapidly (2 months) obtained in five patients, while pseudo-progression was first observed in D. After a grade 3 diarrhea and diabetic ketoacidosis, ICI was stopped in A but the reintroduction one year later did not cause any toxicity. The tolerance was excellent for the 5 other patients. Response was maintained from 16 to 40 months and treatment is ongoing in four patients. C stopped ICI after 26 months (Complete response on PETscan). B had an isolated bone progression after 7 months of ICI which benefited from a local radiotherapy. After almost 2 years of ICI, a multisite progression occurred and crizotinib was proposed.

      Conclusion

      ICIs should be discussed in the treatment of METex14 mut NSCLC.

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    P2.14 - Targeted Therapy (ID 183)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Targeted Therapy
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.14-65 - Efficacy of Dabrafenib Plus Trametinib Combination in Patients with BRAF V600E–Mutant NSCLC in Real World Setting (ID 307)

      10:15 - 18:15  |  Author(s): Helene Doubre

      • Abstract
      • Slides

      Background

      Dabrafenib plus trametinib (D-T) combination is approved in Europe Union for BRAFV600E–mutant metastatic non-small cell lung cancer(NSCLC) but there is few published data’s on this efficacy and tolerance outside clinical trail results.

      Objective: to assess efficacy and tolerance of D-T in real world setting.

      Method

      Retrospective, multicentric study including BRAF V600E-positive advanced NSCLC receiving D-T outside a clinical trial. Overall survival (OS) and progression free survival (PFS) were analyzed in all population and according lines of D-T treatment (first line treatment or subsequent line treatments).

      Result

      the analysis included 40 BRAF V600E advanced NSCLC patients managed in 14 centers; at diagnosis: mean age 71 ±9.6 years , female 55 %, adenocarcinoma 95 %, currents/formers smokers 17.5%/50 %, At D-T initiation: PS 0-1/2 or+: 86.8%/13.2% , loss weight> 5%: 24%, symptomatic disease: 92%, stage IV: 95% , mean metastatic site: 2.3 (main metastatic sites: pleura: 46%, bone: 33%, respectively).Mean line of treatment before D-T: 1.5. D-T was a first line treatment in 22.5 %, second line or more 77.5% (25% received one BRAF TKI before). Median time between diagnosis and D-T treatment was 0.7 [95%CI: 0.2-1.3] months in first line setting and 17.3 [95%CI: 10.8-27.2] months.

      At the time of analysis 67.5% patients were in treatment with D-T and median follow up since beginning of D-T treatment was 8.7[95%CI: 5-12]months in whole population [7,5, 95%CI: 1-12.3]months for patients treated in first line). D-T dose was modified for 32.5.0% of the patients and definitively discontinued for 12,5 % because of severe adverse events.

      Median PFS and OS were not reach and follow up is continued.

      The mature results of PFS and OS (whole population and subgroups) will be showed to the WLCC meeting.

      Conclusion

      Section not applicable

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