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Teresa Morán



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    P1.09 - Pathology (Not CME Accredited Session) (ID 941)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.09-09 - Evaluation of a Novel ROS1 Immunohistochemistry Clone (SP384) for the Identification of ROS1 Rearrangements in NSCLC Patients (ID 12744)

      16:45 - 18:00  |  Author(s): Teresa Morán

      • Abstract

      Background

      After the approval of crizotinib in ROS1 rearranged NSCLCs, the importance of accurately identifying those patients has never been greater. Although the recently updated guideline for molecular testing supports the use of ROS1 IHC as a screening test, to the best of our knowledge, only one ROS1 clone is commercially available and most published comparison studies involve a relatively small numer of positive cases. This situation prompted us to investigate a novel ROS1 IHC antibody in a large series of ROS1 positive NSCLCs samples.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Thirty-nine ROS1 FISH-positive (i.e., gold standard) samples from patients with NSCLCs procured at 22 hospitals were used for this study. In addition, 20 consecutive ROS1 FISH-negative samples from NSCLCs diagnosed at the referral institution were included as negative controls. The material available for all tumors had been formalin-fixed and paraffin-embedded. The specifics of formalin fixation were unknown. All specimens were independently screened for ROS1 expression by two IHC antibodies (clone D4D6 from Cell Signaling Technology and clone SP384 provided by Ventana Medical Systems, Inc.) according to previously published methodology or the manufacturer´s instructions. FISH-validated ROS1-positive external controls were included in all the slides. The slides were reviewed by two pathologists blinded to FISH results. The results of both ROS1 IHC assays were evaluated using a modified H-score: strong cytoplasmic staining (3+), clearly visible using a ×2 or ×4 objective; moderate staining (2+), requiring a ×10 or ×20 objective to be clearly seen; and weak staining (1+), cannot be seen until a ×40 objective is used. Both anti-ROS1 IHC staining results were finally interpreted using a binary scoring system: positive (3+ or 2+) or negative (1+ or 0).

      4c3880bb027f159e801041b1021e88e8 Result

      In ROS1 FISH-negative cases, positive immunoreactivity (3+ or 2+) was observed in 25% and 5% of samples by SP384 and D4D6, respectively. In ROS1 FISH-positive cases, positive expression above the threshold was always present with both antibodies except for one sample that was only stained with SP384. In 4 positive cases (10.3%) by SP384 and 22 positive tumors (56.4%) by D4D6, we noted significant intratumoral heterogeneity, ranging from weak to strong protein expression.

      8eea62084ca7e541d918e823422bd82e Conclusion

      We have studied a very large series of ROS1 FISH-positive NSCLCs with a novel IHC clone, which showed excellent sensitivity. The predominantly homogeneous and intense staining may support the use of a dichotomous scoring approach, before confirmation with FISH or a molecular method.

      Funding: I+D+I 2013-2016/Feder. ISCIII: PI14/01176

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    P1.13 - Targeted Therapy (Not CME Accredited Session) (ID 945)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.13-29 - Overall Response Rate of Nintedanib and Docetaxel in Combination with the Nutraceutical Use of Silibinin in Advanced NSCLC (ID 13239)

      16:45 - 18:00  |  Author(s): Teresa Morán

      • Abstract
      • Slides

      Background

      The bioactive flavonolignan silibinin, the main component of standardized extracts from the seeds of the milk thistle herb Silybum marianum, has been shown to exhibit significant anticancer activity in preclinical models. Silibinin is a direct inhibitor of pSTAT3, a signal transducer and key transcription factor that is associated with chemoresistance in cancer cells. Our group has shown that oral administration of the silibinin-containing nutraceutical Legasil® could represent the first silibinin formulation with proven clinical benefit as an adjunct cancer treatment in patients with brain metastases. Nintedanib is an orally administered, small-molecule triple angiokinase inhibitor of VEGF1–3, PDGFa and b, and FGFR1–3. The LUME-Lung 1 trial showed that nintedanib significantly extended progression-free survival (PFS) and overall survival (OS) in patients with NSCLC adenocarcinoma when added to docetaxel chemotherapy, with no differences in response rate.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Patients with stage IV NSCLC who failed ≥1 prior treatment were eligible for nintedanib/docetaxel combination. We present retrospective data analysis regarding patients that received nintedanib/docetaxel with or without combination with up to 5 capsules (630 mg)/day of Legasil®.

      4c3880bb027f159e801041b1021e88e8 Result

      Fifty-nine patients were enrolled in the study: median age, 60y (range: 43–79); male, 46 (78%). All the cases had adenocarcinoma histology. All patients had received first line therapy and 13 (22%) patients had >2 prior lines of treatment. A higher overall response rate (ORR) was observed in the group receiving Legasil® supplementation: ORR 55.5% versus 22%, p=0.02. No statistically significant differences in the median PFS were observed in the two arms: 2.34 months (95% confidence interval [CI] 1.83–2.91) for nintedanib/docetaxel combination (n=41) versus 4.99 (95%CI 0.94–9.05) for nintedanib, docetaxel and Legasil® triple combination (n=18) (p=0.241) at the data cut-off of January 2018. In the control group (n=41), ORR was greater in patients with known KRAS (n=8) or EGFR (n=3) mutations: 45% versus 13%, p=0.028.

      8eea62084ca7e541d918e823422bd82e Conclusion

      The inhibition of pSTAT3 with silibinin may increase tumor responses to nintedanib/docetaxel combination. In addition, patients with known KRAS or EGFR mutations may show higher tumor responses to nintedanib/docetaxel combination.

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