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M. Alamgeer



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    P1.07 - Poster Session with Presenters Present (ID 459)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: SCLC/Neuroendocrine Tumors
    • Presentations: 1
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      P1.07-004 - Updated Analysis of Phase II Study of HA-Irinotecan, a CD44-Targeting Formulation of Hyaluronic Acid and Irinotecan, in Small Cell Lung Cancer (ID 5868)

      14:30 - 15:45  |  Author(s): M. Alamgeer

      • Abstract

      Background:
      Preclinical studies in small cell lung cancer cell (SCLC) have shown that hyaluronic acid (HA) can be effectively used to deliver irinotecan and selectively decrease CD44 expressing (stem cell-like) tumour cells. The current “proof of principle” study was aimed to replicate these findings by investigating the effect on clinical outcome according to CD44 expression. Final efficacy and bio-marker data on the study is presented.

      Methods:
      Patients with ESLC, having measurable disease, suitable for safe biopsy and able to give informed consent were screened for this study. First 5 patients were treated with HA-irinotecan (150mg/m[2]) and carboplatin (AUC 5), every 3 weeks to evaluate safety data. Subsequent patients were stratified as first line or second line. All second line patients receive open label HA-irinotecan, while first line patients are randomized to receive either HA-irinotecan/carboplatin or irinotecan/carboplatin. The response was measured by CT/PET at baseline, after 1 cycle and every 2 cycles subsequently. Baseline tumour samples were stained for CD44s (standard) and CD44v6 (variant 6). Blood samples for circulating tumour cells (CTCs) were also obtained at the baseline and before each treatment cycle till progression of disease.

      Results:
      Forty (40) patients, median age 66 (range 39-83) were enrolled treated on this study. Seven (7) patients either died or progressed before the first evaluation scan. Of 34 evaluable patients, the overall response rate was 50%, with 4 (12%) complete and 13 (38%) partial responses. Four patients (12%) achieved stable disease while 7 patients (20%) progressed during the treatment. There was no PFS difference in the two first line treatment arms (median 28 weeks in experimental vs 42 week in standard arm) (P = 0.892 HR=0.93, 95% CI 0.36-2042). Median PFS was 14.4 weeks in the second line cohort. The toxicity profile was similar to standard irinotecan, with the incidence of grade III/IV diarrhea seen in the experimental arm of 11% compared with 25% in the standard arm. Biomarker data was available in case of 24 patients, which suggested that there was no difference in response rates or survival according to baseline CD44s or CD44v6 expression. A possible correlation between the number of CTCs and tumour response and relapse was noticed.

      Conclusion:
      HA-irinotecan is well tolerated and has shown activity in the treatment of extensive stage small cell lung cancer. However, no improvement in efficacy was seen in CD44s+ or CD44v6+ SCLC treated with HA-irinotecan. Further strategies to combine HA with other chemotherapeutic agents may be warranted.

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    P3.03 - Poster Session with Presenters Present (ID 473)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Mesothelioma/Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
    • Presentations: 1
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      P3.03-025 - Investigating Phenotypic and Genomic Heterogeneity in Malignant Pleural Mesothelioma (ID 5318)

      14:30 - 15:45  |  Author(s): M. Alamgeer

      • Abstract

      Background:
      Phenotypic and genomic heterogeneity may contribute to the pathogenesis of Malignant Mesothelioma (MM). We have implemented a novel clinical study in which multiple samples of tumour and normal pleura are obtained from individual patients undergoing surgery for the management of MM.

      Methods:
      Patients undergoing routine video-assisted thoracoscopic surgery (VATS) undergo a baseline FDG-PET scan. Extra samples are taken from both PET positive and PET negative areas of pleura, along with normal pleural samples. Corresponding fresh and formalin fixed tissue samples are obtained. Patients are subsequently treated as per standard of care practice, along with detailed clinical follow up and serial PET imaging. Standard H&E will be performed on formalin fixed samples to look for morphological heterogeneity in tumour cells and stroma and the findings will be correlated with PET imaging.

      Results:
      Six (6) patients (4 epithelioid, 1 sarcomatoid and 1 biphasic subtype) with median age of 70 (62-81) have been recruited into the project so far. All patients underwent an FGD-PET scan prior to VATS procedure. Multiple samples from PET avid and PET non-avid areas were collected and stored from 5 out of 6 patients. Preliminary results show that high quality samples were obtained. The H&E analysis shows that tumours from PET avid area are morphologically different to PET not avid areas (Figure 1). Further IHC analysis of various MM specific markers is underway. Figure 1



      Conclusion:
      This preliminary data demonstrate the feasibility of our clinical approach. We therefore propose to create a unique research platform in which MM samples from multiple sites from each patient will be integrated with clinical, imaging and therapeutic response. Further proof-of-principle studies will explore: (i) regional heterogeneity and the response to therapies; (ii) variability in the detection of predictive biomarkers within the same patient; (iii) genomic heterogeneity within MM, and its relationship to mutational changes in normal pleura.