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G.K. Dy



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    O04 - Molecular Pathology I (ID 126)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Pathology
    • Presentations: 1
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      O04.05 - Epidemiology of PI3K pathway alterations in patients with metastatic non-small cell lung cancer (NSCLC): findings from the international BASALT-1 study (ID 1810)

      10:30 - 12:00  |  Author(s): G.K. Dy

      • Abstract
      • Presentation
      • Slides

      Background
      Buparlisib (BKM120) is an oral PI3K inhibitor that inhibits all four isoforms of class I PI3K (α, β, γ, δ) and has demonstrated antiproliferative, proapoptotic, and antiangiogenic activity in multiple preclinical cancer models. NSCLC cell lines with PIK3CA mutations (muts) have demonstrated increased sensitivity to buparlisib in vitro. BASALT-1 – an ongoing, multicenter, open-label, two-stage Phase ll study (NCT01297491) – evaluates the safety and efficacy of single-agent buparlisib in patients (pts) with NSCLC and an activated PI3K pathway. Here we report data on the prevalence of PI3K pathway alterations in pts with squamous (sq) or non-squamous (non-sq) NSCLC prescreened for entry into BASALT-1.

      Methods
      Pts prescreened for BASALT-1 were ≥18 years of age with previously treated metastatic NSCLC of sq or non-sq histology. PI3K pathway activation (defined as PIK3CA mut and/or PTEN mut and/or PTEN negative [neg; <10% protein expression at 1+ by immunohistochemistry]) was measured in archival or newly acquired tumor tissue collected at prescreening. PIK3CA (exons 1, 5, 7, 9, and 20) and PTEN (exons 1–9) muts were detected primarily using Sanger sequencing in a centralized fashion. Local analysis was permitted at selected sites where a SnapShot approach was most commonly used.

      Results
      As of April 10, 2013, 1183 pts had submitted tumor samples to be assayed (1179 tumors had known histology). PI3K pathway activation was detected in 16.0% of sq and 11.3% of non-sq tumors. In sq tumors (N=612), loss of PTEN protein expression (8.2%) was the most common single alteration observed, followed by PIK3CA mut only (3.1%) and PTEN mut only (2.9%). In non-sq tumors (N=567), PTEN mut only was the most common alteration (4.9%), followed by PIK3CA mut only (2.6%) and PTEN neg only (2.1%). Frequencies of co-existing genetic alterations were: PTEN mut + PTEN neg only (1.0% sq vs 0.4% non-sq), PIK3CA mut + PTEN neg only (0.7% sq vs 0.4% non-sq), PIK3CA mut + PTEN mut only (0% sq vs 0.9% non-sq), and PIK3CA mut + PTEN mut + PTEN neg (0.2% sq vs 0% non-sq). No clear gender, age or ethnicity effects were observed (Table). Figure 1

      Conclusion
      The findings from our large dataset indicate that genetic alterations in the PI3K pathway occur in a clinically significant proportion of pts with sq and non-sq relapsed NSCLC. An accurate characterization of PI3K pathway alteration frequencies in NSCLC will help guide the design of future clinical trials of PI3K inhibitors.

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

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Supportive Care
    • Presentations: 1
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      P3.24-055 - Neo-adjuvant Versus Adjuvant Treatment for Non-small Cell Lung Cancer (NSCLC) Less Than Clinical N2 Disease (ID 829)

      09:30 - 16:30  |  Author(s): G.K. Dy

      • Abstract

      Background
      Increasingly, neoadjuvant therapy is being used for the treatment of NSCLC. While several randomized controlled trials have been performed to evaluate this approach in patients with N2 disease, limited data exists in patients less than N2 disease. We examined our experience with neoadjuvant therapy in our institution and compared it to patients receiving adjuvant therapy.

      Methods
      This retrospective analysis included patients with less than clinical N2 disease that underwent curative surgical resection and received either neoadjuvant or adjuvant chemotherapy with or without radiation therapy from 2005 to 2010. Patient characteristics, peri-operative outcomes and survival data were analyzed for patients receiving neoadjuvant vs. adjuvant therapy. Comparison of categorical, continuous and survival variables across groups were performed using chi-square, t-test and Kaplan-Meier methods respectively. Multivariate analyses were performed using Cox Regression analyses.

      Results
      130 patients fulfilled the inclusion criteria – 54 patients had neoadjuvant therapy and 76 patients had adjuvant therapy. Patient characteristics in both comparison groups are summarized in Table 1. No peri-operative deaths were seen in either group. There was no statistically significant difference between the comparison groups with respect to age, gender, race, histology and grade. Patients with neoadjuvant therapy had a higher clinical stage than those that had adjuvant therapy. At a median follow-up of 41.5 months, there was no difference in the overall survival and recurrence free survival of patients in both groups in univariate analyses and in multivariate analyses after adjusting for potentially confounding variables including stage. Patients treated with neoadjuvant therapy had a higher rate of empyema (11.1% vs. 0%; p=0.004) and a trend toward increased arrhythmia and pneumonia than those treated with adjuvant therapy.

      Conclusion
      For NSCLC less than N2 disease, neoadjuvant therapy increases peri-operative morbidity without an improvement in overall and recurrence free survival. For this patient population, the role of neo-adjuvant therapy is questionable. Figure 1Figure 2