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N. Tokaca



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    Epidemiology and outcomes (ID 57)

    • Event: ELCC 2018
    • Type: Poster Discussion session
    • Track:
    • Presentations: 1
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      216PD - Should radical surgery be performed in non-epithelioid malignant pleural mesothelioma? (ID 508)

      14:45 - 15:45  |  Author(s): N. Tokaca

      • Abstract
      • Slides

      Background:
      Non-epithelioid malignant pleural mesothelioma (MPM) has a bad prognosis. We wished to evaluate the impact of multimodality therapy on survival in non-epithelioid MPM.

      Methods:
      Analysis of a prospective database of MPM patients operated on since September 2004. All patients had extended pleurectomy/decortication (ePD) and hyperthermic povidone-iodine pleural lavage (HPL), prophylactic radiotherapy and systemic platinum-based chemotherapy. All patients were followed up until death. PET–CT was used routinely to monitor patients. Survival and prognostic factors were analysed by the Kaplan–Meier method, log–rank test and Cox regression analysis.

      Results:
      139 patients had ePD and HPL. Median age was 64 years and 80% of patients were male.17% of patients had received systemic chemotherapy prior to surgery. 90–day mortality was nil and 39.6% of patients experienced postoperative complications. 9 patients had reoperation within 30 days. Final histopathology showed epithelioid type in 96 patients and non–epithelioid type in 43. Staging (8th ed. TNM classification) was as follows: I, 7.2%; II, 24.4%, III, 54%, IV, 14.4%. Five patients did not receive adjuvant chemotherapy and 4 received less than 4 cycles in total. All other patients received 4–6 cycles of chemotherapy. All patients received prophylactic radiotherapy (21 Gy). 52% of patients received second–line therapies. Two patients had cyberknife therapy and 3 patients had late reoperations for focal relapse. Median follow–up is 50 months and 92 patients have died. Median overall survival is 35 months (95% CI 26.3–43.7) for epithelioid histology versus 18 months (95% CI 15.1–20.9) for non-epithelioid histology (p = 0.000037). Macroscopic complete resection and epithelioid histology are independent prognostic factors of long–term survival at multivariate analysis.

      Conclusions:
      Multimodality therapy including ePD and HPL is safe and well-tolerated. Most patients can receive further therapies when disease progresses. Patients with epithelioid histology achieve prolonged survival. Patients with non-epithelioid histology have a modest survival benefit and radical surgery should be offered only to those with early-stage disease.

      Clinical trial identification:


      Legal entity responsible for the study:
      Dr. Loic Lang-Lazdunski

      Funding:
      Has not received any funding

      Disclosure:
      All authors have declared no conflicts of interest.

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    Poster Display session (Friday) (ID 65)

    • Event: ELCC 2018
    • Type: Poster Display session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 4/13/2018, 12:30 - 13:00, Hall 1
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      149P - Real-world outcomes with first-line afatinib in EGFR mutant NSCLC adenocarcinoma: A single centre experience exploring effects of dose-reduction (ID 274)

      12:30 - 13:00  |  Presenting Author(s): N. Tokaca

      • Abstract
      • Slides

      Background:
      Tyrosine kinase inhibitors of epidermal growth factor receptor (EGFR-TKI) are indicated for first-line treatment of EGFR+ advanced/metastatic NSCLC, having demonstrated superior progression free survival (PFS) and tolerability over chemotherapy in this setting. Afatinib is the only EGFR-TKI to have also shown superior overall survival (OS) over chemotherapy in patients with EGFR 19del mutations, albeit with higher toxicity: 53% and 28% dose reductions (DR) were reported in LUX-LUNG 3 (LL3) and LUX-LUNG 6 (LL6) trials, respectively. Effects of toxicities on treatment delivery and efficacy in the real-world UK population are unknown.

      Methods:
      Retrospective review of outcomes in patients with EGFR+ treatment naïve advanced/metastatic NSCLC treated with afatinib at a single UK centre. Primary endpoint: PFS. Key secondary endpoints: rate of DR; relative dose intensity; toxicities; objective response rate (ORR); PFS according to DR vs no DR; OS overall, by DR vs. no DR, and by mutation type. Survival analyses were performed using Kaplan-Meier methods and compared using the log-rank test.Table:Patient demographics and baseline characteristics (n = 44)

      Patient demographics and baseline characteristic (n = 44)No. (%)
      Age (median, range)63.5 (31–85)
      Gender
       M19 (43.2)
       F25 (56.8)
      Ethnicity
       Caucasian29 (65.9)
       Asian11 (25)
       Other4 (9.1)
      Stage at diagnosis
      2 (4.5)
       IIIA3 (6.8)
       IIIB1 (2.3)
       IV38 (86.4)
      ECOG performance status at start of afatinib
       09 (20.5)
       129 (65.9)
       26 (13.6)
      Comorbidities
       None18 (40.9)
       Mild23 (52.3)
       Moderate3 (6.8)
      EGFR mutation
       Exon 19 del29 (65.9)
       L858R11 (25.0)
       G719X2 (4.5)
       S768I1 (2.3)
       Exon 20 ins1 (2.3)
      Starting dose of afatinib
       40 mg40 (90.9)
       30 mg4 (9.1)


      Results:
      44 patients received first-line afatinib (30–40 mg) between September 2012 and July 2017. Patient characteristics are shown in the Table. 70% patients had at least one DR, 29% during the first cycle. Relative dose intensity was 77.1%. The most common toxicity was diarrhoea (32%), followed by skin rash (22%) and paronychia (18%). Out of 42 evaluable patients, 74% achieved partial response (56% and 67% in LL3 and LL6, respectively). Disease control rate was 93% (LL3: 90%, LL6: 93%). After median follow-up of 26 months, 27/42 patients had disease progression or death on afatinib, 10 patients remained on afatinib and 5 switched to other EGFR-TKI due to intolerable toxicities. mPFS was 12.3mo (LL3: 11.1mo, LL6: 11mo). mPFS in patients with a DR was 22.7mo vs. 12.3mo if no DR (HR 0.69, p = 0.38). Median OS was 31.4mo (LL3: 28.2mo, LL6: 23.1mo). There was no significant difference in mOS for patients with DR vs. no DR (31.4 vs 24.4mo, HR 1.51, p = 0.46). There was a trend towards greater OS for patients with EGFR del19, but not statistically significant (p = 0.23). EGFR T790M testing was available for 19 patients after progression on afatinib, with 6 positive for T790M, all of whom went on to a third-generation EGFR-TKI.

      Conclusions:
      Dose reductions on afatinib are required in a majority of real-world patients, with no significant detrimental impact on efficacy and long-term survival outcomes which, in our cohort, were consistent with trial data.

      Clinical trial identification:


      Legal entity responsible for the study:
      Royal Marsden Hospital

      Funding:
      Has not received any funding

      Disclosure:
      M. O'Brien: Advisory work for BI. J. Bhosle: Honoraria from Boehringer Ingelheim. S. Popat: Consulting/advisory for Boehringer Ingelheim. All other authors have declared no conflicts of interest.

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