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C. Brzezniak



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    MO03 - Thymic Malignancies (ID 123)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 1
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      MO03.07 - Clinical activity of sunitinib in patients with thymic carcinoma (ID 3114)

      10:30 - 12:00  |  Author(s): C. Brzezniak

      • Abstract
      • Presentation
      • Slides

      Background
      There are no standard treatments for patients with advanced thymic epithelial tumors (TET) in whom chemotherapy has failed. A subset of TETs over-express and harbor activating mutations of KIT. Moreover, expression of angiogenic markers correlate with invasiveness of TETs. This two-center phase II study was conducted to evaluate efficacy of sunitinib, a multi-targeted tyrosine kinase inhibitor that blocks angiogenic and other growth factors in TETs.

      Methods
      Patients with TET who had progressive disease following at least one platinum-based chemotherapy were enrolled. Sunitinib was administered orally at 50 mg once daily in 6 week cycles for 4 weeks followed by 2 weeks off until disease progression. Tumor response was assessed by computed tomography scans every 6 weeks. KIT mutations were assessed in archival tissue. Primary end-point was objective response rate in parallel cohorts (thymoma, thymic carcinoma).

      Results
      Between May 2012 and June 2013, 22 patients with thymic carcinoma [median age 58 (40-81); males 59%] and 16 with thymoma [median age 54 (31-74); males 44%] enrolled. Median of 4 (range, 1-7) and 3 (range, 1-8) cycles were administered in patients with thymic carcinoma and thymoma respectively. Among 19 evaluable patients with thymic carcinoma, there were three partial responses (16%) and 10 minor responses (50%) (Figure). Thirteen patients had stable disease (68%) and three progressive disease (16%). After median follow up of 7.8 months, the median progression-free survival was 6.2 months and 6-month survival probability 85%. In contrast, only one out of 16 patients with thymoma had a partial response (6%). Twelve patients had stable disease (75%) and three progressive disease (19%). After median follow up of 6.4 months, median progression-free survival was 5.5 months and 6-month survival probability 90.9%. Grade 3 or 4 sunitinib-related adverse events which occurred in >10% of patients included neutropenia (18%), thrombocytopenia (23%), leucopenia (18%), lymphopenia (45%), fatigue (36%), mucositis (32%) and hypertension (18%). Three patients (14%) has symptomatic decline in left ventricular ejection fraction which improved with medical management and discontinuation of sunitinib. KIT mutations were absent in tumors of 20 patients who underwent mutational analysis.Figure 1

      Conclusion
      In this phase II trial, sunitinib demonstrated anti-tumor activity unprecedented for a targeted agent in previously treated patients with thymic carcinoma. Activity was modest in thymoma. These results are intriguing as response rates of thymic carcinomas are usually lower than that for thymomas. KIT mutations did not predict responses. Ongoing exploratory analyses are evaluating biologic determinants of activity and mechanisms of resistance.

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    P2.22 - Poster Session 2 - Epidemiology, Etiology (ID 167)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Prevention & Epidemiology
    • Presentations: 1
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      P2.22-011 - Racial/Ethnic Variation Among Non-Small Cell Lung Cancer (NSCLC) Patients in the United States Department of Defense (ID 2925)

      09:30 - 16:30  |  Author(s): C. Brzezniak

      • Abstract

      Background
      Non-small cell lung cancer (NSCLC) comprises 87% of all lung cancer in the United States with the vast majority diagnosed in advanced stage. Military personnel have higher smoking rates compared to the general population and consequently an increased incidence of lung cancer. We set out to examine whether there were variations in smoking rates and outcomes among patients diagnosed with NSCLC, based on self described ethnicity, in the United States Military and their dependents who receive equal and open access to healthcare in the Department of Defense (DOD) medical system.

      Methods
      We identified 4,547 patients ≥18 years, with an initial diagnosis of NSCLC from January 2003- March 2013 in the DOD Cancer Registry and categorized into the following self described ethnic groups: Caucasian, African American, Hispanic and Asian/Pacific Islander (PI). Differences in patient characteristics by race were compared using Chi-square and t-test. Kaplan Meier curves and Cox proportional hazards regression assessed overall survival.

      Results
      There were 3434 (76%) Caucasian, 533 (12%) African Americans, 468 (10%) Asian/PI, and 112 (2%) Hispanics who met the study inclusion criteria. Mean age at diagnosis was highest among Caucasians (67 yrs) followed by Asian/PI (64 yrs), Hispanics (63 yrs) and African Americans (62 yrs). A large majority of Caucasians (87%) and African Americans (86%) had a history of tobacco use, followed by Hispanics (74%) and Asian/PI (65%). Asian/PIs were also more likely to be female, married, have adenocarcinoma histology and were more likely to be sporadic cases (no family history) compared to the other self described ethnic groups. Asian/PIs had significantly higher unadjusted overall survival (Log rank p = 0.0012) and in the multivariate survival analysis, adjusting for age, sex, race, stage, histology, comorbidity, tobacco history, alcohol history, family history, and marital status, Asian/PI patients demonstrated a 20% lower risk of death (Table 1) compared to Caucasian patients. There was no difference in mortality risk between Caucasian and African Americans, and Caucasian and Hispanics.

      Conclusion
      In this military cohort, equal open access to care in NSCLC patients resulted in similar overall survival among Caucasian, African Americans and Hispanics with significantly higher OS among Asian/PIs. Racial disparities in survival often seen in US civilian populations were not seen in this study of patients treated in the military health system, perhaps due to more equal access to health care. Continued research evaluating treatment patterns and outcomes in the military relative to the general population is warranted.

      Table: Cox Proportional Hazards Regression of Overall Survival
      RACE N HR 95% CI
      Caucasian 3434 ref
      African American 533 1.001 0.89-1.12
      Asian/Pacific Islander 468 0.803 0.71-0.91
      Hispanic 112 0.984 0.77-1.26