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L. Benesova



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    P2.11 - Poster Session 2 - NSCLC Novel Therapies (ID 209)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P2.11-047 - Sequential treatment with erlotinib and pemetrexed in pretreated patients with lung adenocarcinoma. (ID 3292)

      09:30 - 09:30  |  Author(s): L. Benesova

      • Abstract

      Background
      Erlotinib and pemetrexed are novel agents used for the treatment of patients with advanced-stage NSCLC. Both are frequently used for the treatment of patients after failure of first-line chemotherapy. Sequential treatment strategies have become a very interesting topic in current oncology research. The role of sequential treatment in NSCLC has not been elucidated yet. Thus, we conducted this retrospective study to compare the efficacy of second-line pemetrexed monotherapy followed by third-line erlotinib (P-E) to treatment with the reverse sequence (E-P).

      Methods
      Clinical data of 57 patients with advanced (IIIB/IV) lung adenocarcinoma harboring wild-type epidermal growth factor receptor (EGFR) gene were analysed. 31 patients were treated with P-E and 26 patients with E-P sequence. Genetic testing was performed using PCR direct sequencing. The terminations of PFS and OS, as well as the estimations of survival probabilities, were performed using Kaplan Meier survival curves; all point estimates were accompanied by 95% confidence intervals. The differences in survival were tested using the log-rank test.

      Results
      The median progression-free survival (PFS) for patients treated with the P-E sequence was 3.6 months compared to 7.8 months for patients treated with E-P sequence (p=0.029). The median overall survival (OS) for patients treated with P-E sequence was 7.9 months compared to 26.3 months for patients treated with E-P sequence (p=0.006).

      Conclusion
      The study results proved significant improvement of both PFS and OS for patients treated with the E-P sequence as compared to the P-E sequence. Although the study was limited, its findings could have a great impact on the treatment of advanced-stage NSCLC. Thus, the role of the sequential treatment of NSCLC should be confirmed in a prospective randomised study in the future.

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    P3.02 - Poster Session 3 - Novel Cancer Genes and Pathways (ID 149)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P3.02-020 - NSCLC Molecular portrait of the sample of Czech population and indications of targeted therapy (ID 3119)

      09:30 - 09:30  |  Author(s): L. Benesova

      • Abstract

      Background
      Molecular therapy targeted on tumour driving mutations should improve quality of life, PFS and overal survival in NSCLC patients. While EGFR mutations are widely accepted as targets for gefitinib and erlotinib in the first line treatment of advanced NSCLC, recently, translocation of EML4-ALK as well as amplification of ROS1, are used as guides for indication of crizotinib. Some other genetic changes, such as EGFR amplification, c-Met amplification, PIK3CA mutations and KRAS mutations are expected to serve as prognostic or predictive factors of targeted therapy currently or in near future.

      Methods
      We analyzed molecular predictors which were routinely tested at our department starting in 2004. We focus on EGFR mutations, EGFR gene amplifications, KRAS mutations, EML4-ALK translocations, c-Met amplifications and PIK3CA mutations. We analyzed the frequency of genetic changes and , where applicable, their impact on PFS and OS. We have also analysed comparability of PCR based detection (multiplex ligation-dependent probe amplification, MLPA) an FISH for EGFR gene amplifications.

      Results
      In the group of 890 NSCLC patients we found EGFR mutations on exon 19 in 62 cases, EGFR mutations on exon 21 in 24 patients. KRAS mutations were found in 141/819. Translocations of EML4-ALK were found in 7/203, c-Met amplifications in 5/104, EGFR amplifications in 11/34 and PIK3CA mutations in 8/220 patients. We confirmed a high correlation between FISH and MLPA-based testing of EGFR amplifications, as well as agreement of PFS and OS of both groups. However, EGFR gene amplifications were not prognostic, nor predictive marker of TKI therapeutic efficacy. Positive predictors of such treatment were in accordance with the literature and our expectiations, EGFR mutations for the treatment with gefitinib and erlotinib, and EML4-ALK translocations for crizotinib. We identified KRAS G12C mutation as the only negative predictor of EGFR inhibitor treatment. One hundred patients were defined as triple negative tumors (EGFR, EML4-ALK, KRAS negative). Some of our patiens had some combinations of genetic changes, such as concurrent EGFR and KRAS mutations, mutations and amplifications of EGFR gene and, in one patient, mutations and amplifications of EGFR, EML4-ALK translocation and c-Met amplification.

      Conclusion
      Precious morphologic and genetic investigations of NSCLC tumour tissue should serve as a guide for targeted therapy. However, in our population of non-squamous tumour lesions, we found predominantly a triple negative tumour type which should continue to be treated by first line chemotherapy.

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    P3.06 - Poster Session 3 - Prognostic and Predictive Biomarkers (ID 178)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P3.06-029 - Predictive role of serum tumor markers in NSCLC patients treated with erlotinib (ID 2433)

      09:30 - 09:30  |  Author(s): L. Benesova

      • Abstract

      Background
      Erlotinib is an epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitor. Clinical trials proved its efficacy in patients with advanced-stage NSCLC. Although, activating EGFR gene mutations are currently the strongest predictor of erlotinib efficacy, the majority of NSCLC patiens harbor wild-type EGFR gene and moreover there is still a large proportion of patients in whom it is not feasible to acquire an adequate tissue for EGFR mutation analysis. We conducted this retrospective study aiming to prove the predictive role of tumor markers in patients with advanced-stage NSCLC treated with erlotinib.

      Methods
      144 patients with advanced-stage (IIIB, IV) NSCLC were treated with erlotinib (150 mg daily). Pretreatment serum levels of CEA, CYFRA 21-1, NSE and TK were assessed. Comparison of patients’survival (PFS and OS) according to the level of assessed tumor markers was performed using the log-rank test.

      Results
      Median PFS and OS for patients with normal CEA levels was 2.9 and 16.1 vs. 1.9 and 8.6 months in patients with high CEA levels (p = 0.046 and p = 0.116). Median PFS and OS for patients with normal CYFRA 21-1 levels was 3.4 and 23.8 vs. 1.9 and 6.1 months in patients with high CYFRA 21-1 levels (p < 0.01 and p < 0.01). Median PFS and OS for patients with normal NSE levels was 2.1 and 9.8 vs. 1.1 and 3.8 months in patients with high NSE levels (p = 0.051 and p = 0.022). Median PFS and OS for patients with normal TK levels was 2.1 and 23.7 vs. 2.0 and 8.5 months in patients with high TK levels (p = 0.110 and p = 0.037).

      Conclusion
      The study proved that high pretreatment levels of CEA, CYFRA 21-1 and NSE predict low efficacy of erlotinib treatment in patients with advanced-stage NSCLC. Assessment of these tumor markers is a good predictive tool for erlotinib treatment efficacy especially for those patients with unknown EGFR mutation status.