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Marko Jakopovic



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    P2.09 - Mesothelioma (ID 710)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Mesothelioma
    • Presentations: 1
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      P2.09-004 - PD-L1 Protein Expression Is Negative Prognostic Factor in Malignant Pleural Mesothelioma in Central Europe (ID 9558)

      09:30 - 09:30  |  Author(s): Marko Jakopovic

      • Abstract
      • Slides

      Background:
      Early data on immune-checkpoint blockade with PD-1 inhibitors show promising response rates and survival benefit mainly in PD-L1 positive malignant pleural mesothelioma (MPM) patients. Reported rate of PD-L1 positivity of MPM is between 20-40%. However, the role of PD-L1 protein expression positivity in prediction of a response to PD-1/PD-L1 inhibitors remains controversial. We assessed the prognostic value of PD-L1 expression in patients with MPM in central Europe.

      Method:
      We evaluated protein expression of PD-L1 in formalin-fixed paraffin-embedded surgical specimens of 176 MPM patients from Austria, Croatia, Hungary and Slovenia. PD-L1 antibody clone E1L3N (Cell Signaling) was used. Cut-off point of >10% of PD-L1-positive tumor cells at any staining intensity was correlated with clinicopathologic characteristics (age, gender, IMIG clinical stage, histology (epithelioid vs non-epithelioid) and survival).

      Result:
      There were altogether 49 females and 127 males, median age 63 years. PD-L1 protein expression of >10% was observed in higher proportion in a patient with higher IMIG stage (III+IV vs. I+II), as well as in patients with non-epithelioid histology, later being also statistically significant (p=0.0026). Median survival of patients with high PD-L1 expression (>10%) in tumor cells was significantly shorter in comparison with patients demonstrating lower PD-L1 expression (26 vs. 67 weeks respectively, p<0.001). PD-L1 expression (>10%) proved to be an independent prognostic factor in a multivariate cox regression analysis (hazard ratio [HR] 2.902; 95% confidence interval [CI] 1.425 to 5.937; p = 0.003).

      Conclusion:
      High expression of PD-L1 on tumor cells (>10%) is negative independent prognostic factor in malignant pleural mesothelioma regardless of histology.

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    P3.01 - Advanced NSCLC (ID 621)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
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      P3.01-059 - First Experience with Osimertinib in Patients with Newly Developed T790M Mutation Previously Treated with EGFR – TKIs in Croatia (ID 9878)

      09:30 - 09:30  |  Presenting Author(s): Marko Jakopovic

      • Abstract

      Background:
      EGFR T790M mutation is responsible for 50 to 60% cases of resistance to first and second generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) in patients who have lung cancer with an activating EGFR mutation.

      Method:
      We administered osimertinib 80 mg once daily in 11 patients with advanced lung cancer who had radiologically documented disease progression after previous treatment with first and second-line EGFR tyrosine kinase inhibitors.

      Result:
      We treated 11 patients with osimertinib with stage IV lung adenocarcinoma. Three patients were males and eleven were females, median age 64 (raging from 54 to 82). Seven patients were never smoker, and four were ex-smokers. Ten patients had initially deletion 19 in EGFR gene and one had L858R in exon 21 and then developed T790M mutation. In all patients T790M was proven from tumor tissue. Majority of patients were ECOG 1. All patients were previously treated with first or second line EGFR TKIs (erlotinib, gefitinib or afatinib) and had radiologically documented disease progression. Two patients received osimertinib in 2[nd] line setting, three patients in third line setting, 3 in fourth, one in fifth, one in seventh and one even in tenth line setting. Median time to response was 4 weeks (raging from 3 to 7). All11 patients had partial response (PR) with progressive disease in only one patient after 12 months of treatment. Median duration of response is at the moment 12.5 months, (4 to 60). No significant side effects were observed.

      Conclusion:
      Osimertinib is highly active in patients with lung adenocarcinoma which harbor EGFR T790M mutation who had had disease progression during prior therapy with EGFR tyrosine kinase inhibitors. Efficacy in Croatian population is similar to previously observed. There were no serious side effects of treatment.