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J. De Grève



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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): J. De Grève

      • 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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    O26 - Support and Palliation II (ID 140)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Nurses
    • Presentations: 1
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      O26.06 - Impact of geriatric assessment on treatment decisions in older lung cancer patients. (ID 1419)

      16:15 - 17:45  |  Author(s): J. De Grève

      • Abstract
      • Presentation
      • Slides

      Background
      This study aims to investigate the influence of a geriatric assessment (GA) on cancer treatment decisions in older lung cancer patients (pts). We also studied the changes in functionality during treatment and the occurrence of severe chemotherapy-related toxicity.

      Methods
      For this analysis, we selected the lung cancer cohort that was part of a larger study on GA in older cancer pts in 6 tumor types in two Belgian university hospitals[1]. Between July 2009 and September 2011, pts aged 70 years or older with a newly diagnosed or progressive lung cancer were evaluated at baseline using a uniform GA including geriatric screening with G8 and the Flemish Triage Risk Screening Tool (fTRST), pain, social data, Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL), fall history, Mobility-Tiredness Test (MOB-T), Mini Mental State Examination (MMSE), Geriatric Depression Scale (GDS-15), Mini Nutritional Assessment (MNA), ECOG-Performance Status (ECOG-PS), Charlson Comorbidity Index (CCI) and poly-pharmacy assessment. GA results were communicated to the treating physician and, after the treatment decision, the physician was interviewed using a predefined questionnaire focusing on unknown geriatric problems revealed by GA and impact on cancer treatment decisions. Between two and three months of follow-up, functionality was reassessed and severe toxicity in pts receiving chemotherapy was recorded.

      Results
      Seventy three lung cancer pts were included with a median age of 76 years; 82.2% were non-small cell lung cancer (NSCLC) and 74% were stage IV. Treatment was modified from standard according to standard clinical assessment (including age) in 56.1%. GA revealed unknown geriatric problems in 25.8% of cases, leading to a geriatric intervention in 10.6%. 30% of physicians consulted the GA before final treatment decision and in three pts (4%) only this led to a modification of the proposed treatment: dose reduction, no chemotherapy or no radiotherapy. At follow up (n=50), functional decline was observed in 24% and 54% of pts for ADL and IADL, respectively. Grade III-IV toxicity occurred in 14/42 pts treated with chemotherapy (33%), mainly non-haematological (64%).

      Conclusion
      This analysis indicates that the treatment of older lung cancer pts is often influenced (deviated from standard) by standard clinical assessment and age. Although GA revealed previously unknown information in 25.8% of pts, only a minority of physicians consulted these results before the final cancer treatment decision. There was little impact on geriatric intervention and even less on cancer treatment decision. This discrepancy reveals the need to get physicians treating lung cancer acquainted with GA and geriatric interventions in an attempt to decrease chemotherapy related toxicity and improve quality of care. Further evaluation of GA and geriatric interventions in larger pt groups as well as their implementation in clinical practice is warranted.

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