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M. Khasraw



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    P2.13 - Poster Session 2 - SCLC (ID 201)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P2.13-004 - Lithium as a neuroprotective agent in patients undergoing prophylactic cranial irradiation (PCI) for small cell lung cancer (SCLC): the TULIP study (ID 2069)

      09:30 - 09:30  |  Author(s): M. Khasraw

      • Abstract

      Background
      Somnolence syndrome and cognitive dysfunction are devastating complications of cranial irradiation. Lithium (Li) has neuroprotective properties, such as induction of neuroglial growth after radiation and reduction of cognitive loss in models of cranial irradiation (PCI). It has a well-understood safety profile. PCI is offered to SCLC responders to chemo and radiotherapy. We are assessing feasibility and subsequently efficacy of lithium as a neuroprotective agent in people receiving cranial irradiation.

      Methods
      Twenty SCLC patients treated with PCI are randomised in an open label multicentre stratified feasibility study, (TULIP), to PCI +/- Li. Li is commenced after PCI at 250mg daily, and increased by 250 – 500 mg based on plasma levels for a period of 6 weeks, the average time to develop somnolence syndrome. Patients with histologically or cytologically confirmed SCLC with complete or partial response to chemotherapy and lung irradiation with no major comorbidities and good performance are eligible. Cognitive assessments are done at baseline, after Li therapy, at 3, 6 and 12 months using CogState interactive tools assessing aspects of executive function, memory and attention. Additionally, the Cognitive Failures Questionnaire, Centre for Epidemiological Studies Depression Scale, and Epworth Sleepiness Scale evaluation are completed. Feasibility is the primary endpoint of TULIP. Secondary endpoints include neurocognition and safety. FDG-PET and gadolinium MRI before and 6 weeks after Li or placebo assessing grey matter volumetrics within the hemispheres before and after Li. Differences in regional cerebral metabolic rate for glucose consumption, between baseline and after Li will be evaluated using Parametric Mapping.

      Results
      N/A

      Conclusion
      There are currently 5 patients enrolled in TULIP. Subsequent to TULIP, the definitive 2nd Li Protection Study (2LiP) will commence, aiming to randomise 138 patients with various malignancies and brain metastases treated with whole brain radiotherapy +/- Li to measure impact of Li on cognition, mood and quality of life.

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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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      P3.11-012 - Epidermal growth factor receptor tyrosine kinase inhibitors in advanced squamous cell carcinoma of the lung. (ID 1267)

      09:30 - 09:30  |  Author(s): M. Khasraw

      • Abstract

      Background
      Tyrosine Kinase inhibitors (TKIs) with gefitinib or erlotinib targeting the epidermal-growth factor receptor (EGFR) are a well-established therapy in the treatment of metastatic pulmonary adenocarcinoma, particularly in patients with activating EGFR mutations. EGFR mutations are rarely found in squamous cell carcinomas (SCC) of the lung. There is conflicting data supporting the efficacy of EGFR inhibitors in advanced SCC of the lung. In this analysis we examined the impact of EGFR TKIs on progression-free survival (PFS) and overall survival (OS) in unselected patients with SCC of the lung.

      Methods
      We searched for Randomised controlled trials (RCTs) comparing EGFR-TKIs alone with placebo (PL) in patients with metastatic non-small cell lung cancer. RCTs in the front-line, maintenance and subsequent therapies were included. The primary outcome was PFS in the SCC population. We used published hazard ratios (HRs), and when not available unpublished data was sought. Non-adenocarcinoma was used as a surrogate for SCC when analysis was available by specific histology. Pooled estimates of treatment effect on OS and PFS were calculated using the random-effects inverse variance weighted method.

      Results
      Eight eligible RCTs were included: 2 first line, 6 second-line or beyond, evaluating 1781 patients (EGFR TKI v PL). Data was available for analysis of OS in 4 studies (second-line; N = 1420) and for PFS in 4 studies (three second-line, one first-line; N = 788). EGFR TKIs significantly prolonged PFS, with a hazard ratio of 0.77 [95% CI 0.65 – 0.92]. OS was prolonged with a hazard ratio of 0.88 [95% confidence interval (CI) 0.78 – 1.00]. Efforts to obtain further missing data from the other studies to complement the analysis are on-going.

      Conclusion
      EGFR mutations are rare in SCC of the lung, yet EGFR TKIs have a significant PFS benefit and (less certain) OS benefit compared to placebo in unselected patients with advanced pulmonary SCC, and should be considered as a therapeutic option in patients with advanced SCC of the lung. EGFR mutation independent mechanisms may explain efficacy of EGFR inhibitors in this setting. An individual patient data meta-analysis is warranted to further characterize the OS benefit.