Author of

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  P3.24 - Poster Session 3 - Supportive Care (ID 160)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Supportive Care
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/30/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 12886

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    P3.24-033 - A case of lung adenocarcinoma harboring both a KRAS mutation and an EML4-ALK fusion gene with response to crizotinib. (ID 1998)

    09:30 - 09:30  |  Author(s): M.E. Menefee
    • Abstract

    Background
    Echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion genes occur in approximately 4-7% of patients with adenocarcinoma of the lung (ACL). These tend to occur in individuals with limited or no tobacco exposure and largely occur in exclusion of KRAS mutations. The presence of a KRAS mutation is associated with a worse prognosis and predicts lack of response to targeted therapeutics such as crizotinib. We believe this to be the first case reported of a concurrent KRAS mutation and EML4-ALK translocation with a subsequent response to crizotinib.

    Methods
    Not applicable

    Results
    A 56 yo White female smoker had a recent diagnosis of cirrhosis due to hepatitis B and C. Imaging for her liver revealed an incidental finding of bilateral lung opacities, both of which were suspicious for malignancy. A biopsy of the LLL lesion confirmed ACL. Resection of the superior segment of the LLL was performed and confirmed a well-differentiated ACL with BAC features (T1b, N0, M0). Analysis revealed a KRAS mutation (p.G13C (c.37G>T); EGFR and EML4-ALK analysis were not performed. The right-sided lesion was observed. One year later, disease progression was identified in the right hilum and mediastinum. EBUS confirmed the presence of ACL in levels 10R and 4R lymph nodes. Molecular analysis again confirmed the presence of a KRAS mutation, albeit a different mutation (p.G12A (c.35G>C) than was observed in the left lung. There was no ALK gene rearrangement. She was treated with concurrent chemoradiation with cisplatin as the radiosensitizer in light of her pre-existing grade 2-3 thrombocytopenia from her underlying liver disease. She received 38 out of a planned 60 Gy due to thrombocytopenia and subsequent interruptions in therapy. Nonetheless, she did respond to therapy, but she had a local recurrence less than 8 months after therapy was terminated. At the time of progression, the patient sought further surgical intervention and a pneumonectomy was offered; however, mediastinoscopy confirmed the presence of adenocarcinoma in a level 7 node and plans for further resection were aborted. Mutational analysis confirmed the presence of the activating KRAS mutation, (p.G12A (c.35G>C) and negativity for an EGFR mutation; however, an EML4-ALk translocation was identified in 20% of cells analyzed. The patient was treated with crizotinib. After 8 weeks of therapy, PET/CT demonstrated objective evidence of response to therapy with the maximum SUV decreasing from a baseline of 11.3 to 6.8, with the lesion remaining stable in size. Therapy was well-tolerated, although the patient had an unexpected finding of normalization of her platelet count while on therapy with crizotinib.

    Conclusion
    This unusual case of a female smoker with a co-existing EML4-ALK translocation and activating KRAS mutation highlights several important points: 1. EML4-ALK translocations are not mutually exclusive of KRAS mutations in all patients with ACL. 2. Discordance in EML4-ALK translocation status can occur in metastatic deposits. 3. Individuals harboring both an EML4-ALK translocation and a KRAS mutation can respond to crizotinib. 4. Commonly used algorithms for molecular testing in ACL do not identify all patients who may benefit from molecularly targeted therapies.