Author of

• 11745

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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
  • Moderators:
  • Coordinates: 10/29/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 11778

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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): L. De Petris
    • 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.