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S. Mindus



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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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      P2.11-033 - ALK-EML4-testing in non-small cell lung cancer:<br /> Experiences from Karolinska University Hospital in Sweden (ID 2360)

      09:30 - 09:30  |  Author(s): S. Mindus

      • Abstract

      Background
      Overall survival (OS) in lung cancer is poor but not without heterogeneity. Molecular pathways and “driver mutations” have been identified in the struggle to improve prognosis and treatment outcome. Some constitute predictive factors for the use of new drugs: tyrosine kinase inhibitors (TKI) such as erlotinib and gefitinib target mutations within the EGFR-gene and crizotinib ALK-translocations. The presence of the two molecular features are usually mutually exclusive. Crizotinib is a newly registered drug in Sweden. Our aim was to define the clinical importance of molecular pathological testing for ALK-EML4-translocations in non-small lung cancer (NSCLC).

      Methods
      We have retrospectivly examined all histological and cytological sampling for molecular testing on NSCLC-patients at Karolinska University Hospital since 2010. 3 complementary methods to identify ALK-EML4-translocations were used: fluorecense-in-situ-hybridisation (FISH) with Vysis ALK break apart probe, immunohistochemistry (IHC) with ALK-EML4 specific AB and real time PCR with an in-house developed method able to detect the five most common fusiontranscripts with inversion INV(2)(p21p23).

      Results
      211 FISH-test were conducted, whereof 70 performed on 160 consecutive surgically removed NSCLC. A total of 30 ALK-EML4-translocations were identified, 3 of which amongst the 70 surgical samples. No case of concomittant ALK-EML4-translocation and mutation in the EGFR-gene was identified. The characteristics of ALK-EML4 positive patients were as follows: 19 were women and 11 men with an average age of 58.2 years. 20 were never smokers, 1 current smoker, 9 ex smokers with an average time of 20.5 years since smoking cessation. Adenocarcinomas represented 29 cases and adenosquamous cancer 1 case (currently smoking woman). Staging according to IASLC 7[th] edition showed : 4 patients in stage I, 1 in stage II, 7 in stage III and 18 in stage IV. 16 patients, all with metastatic disease, were treated with crizotinib (15 with 250mg 1x2 and 1 patient with 200mg 1x1). Crizotinib was given to: 0 patients as 1[st] line, 4 patients as 2[d] line, 6 as 3[d ]line, 5 as 4[th] line and 1 as 5[th] line. At time of data collection 9 patients had discontinued crizotinib-therapy. 7 patients had ongoing treatment with an average duration of 125 days. 12/16 patients obtained partial remission, 3 stable disease and 1 disease progression. 3/9 discontinued crizotinib-therapy due do severe side effects: 1 due to persistant visus toxicity grade ≥2, 1 due to pneumonitis occuring at treatment day 42 and 1 due to liver toxicity with CTCAE grade ≥2 occurring at treatment day 37. Only the case with pneumonitis resultated in death at day 43. No QTc-syndromes and no hematological toxicity CTCAE grade ≥3 occurred.

      Conclusion
      Identifying patients with ALK-EML4-translocations, the predictive factor for crizotinib-treatment, offers new treatment options and realistically balanced hope in the severe setting of metastatic NSCLC. In our experience, the predictive value of a positive ALK-EML4-test is high on histological material and crizotinib offers good treatment outcomes after progression on platinum-based chemotherapy but for shorter time than what is expected for TKIs in patients with activating EGFR-mutations.

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    P3.11 - Poster Session 3 - NSCLC Novel Therapies (ID 211)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P3.11-031 - The clinical importance of EGFR-testing in non-small cell lung cancer:<br /> Three year experience from Karolinska University Hospital in Sweden (ID 2377)

      09:30 - 09:30  |  Author(s): S. Mindus

      • Abstract

      Background
      Lung cancer remains the most leathal form of cancer. Overall five-year survival rate is poor but not without heterogeneity. The struggle to improve prognosis and treatment outcome is ongoing. Molecular pathways and “driver mutations” have been identified, some of which can be specifically targeted by new drugs. Mutations within the APT-binding domain of the EGFR gene constitute a predictive factor for the use of tyrosine kinase inhibitors (TKI) such as erlotinib or gefitinib. Our aim was to define the clinical importance of molecular pathological testing for activating EGFR-mutations in non-small lung cancer.

      Methods
      We have retrospectivly examined all histological and cytological sampling for molecular testing on NSCLC-patients in the two lung cancer centra in Stockholm, Sweden (Karolinska University Hostpital: sites of Solna and Huddinge) between 2009 and 2011. All samples with positive outcome were identified and clinical data from all patients in advanced stages of disease were collected.

      Results
      565 samples were collected for EGFR-mutation analysis. Mutations were identified in 66 cases (11,7%). Both cytological and histological material were analyzied (n=23 and 21 respectively). 42 tumors were adenocarcinomas, 1 was a large cell carcinoma and 1 was a squamous cell carcinoma. 29 presented deletion in exon 19 and 14 mutations in exon 21, whereof 21 and 12 respectively were women. 1 patient (male) presented a constitutive deletion in exon 20. 44 patients had metastatic disease. Clinical data from these patients were further analyzed. 21 were never smokers, 21 former smokers with 28 years in average since smoking cessation and 2 were current smokers. All patients recieved TKI-treatment, whereof 24 as 1[st] line, 14 as 2[nd] line and 6 as a later line. Partial remission was obtained in 77% of cases and stable disease in 11%. 2,2% of patients developed progressive disease according to RECIST-criteria during TKI-treatment. At time of data collection, 16 patients had died. The remaining 28 patients had ongoing TKI-treatment for 400 days on average and a median survival of 21 months.

      Conclusion
      A positive mutation test on either cytological or histological material carries a high predictive value for TKI-treatment. TKIs offer good and durable treatment results in patients with advanced NSCLC and activating EGFR-mutations. Thus, identifying this subset of patients offers new treatment options and realistically balanced hope in the severe setting of metastatic NSCLC.