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Daniel Shao Weng Tan



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    Genetic heterogeneity and clonal evolution (ID 32)

    • Event: ELCC 2019
    • Type: Special Symposium
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 4/12/2019, 10:30 - 12:00, Room B
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      Elucidating EGFR evolution (ID 82)

      10:30 - 12:00  |  Presenting Author(s): Daniel Shao Weng Tan

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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    Lunch & Poster Display session (ID 58)

    • Event: ELCC 2019
    • Type: Poster Display session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 4/11/2019, 12:30 - 13:00, Hall 1
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      145P - Clinicopathological characteristics and outcome of advanced ROS1-positive non-small cell lung cancer in Asian patients (ID 332)

      12:30 - 13:00  |  Author(s): Daniel Shao Weng Tan

      • Abstract

      Background

      ROS1 rearrangement is a rare and distinct molecular subset of non-small cell lung cancer (NSCLC), sensitive to tyrosine kinase inhibitors (TKI) targeting the ROS1 kinase domain. We describe the prevalence, clinicopathological characteristics and clinical outcomes of advanced ROS1 positive NSCLC patients (pts), including concomitant mutations and brain metastases.

      a9ded1e5ce5d75814730bb4caaf49419 Methods

      We reviewed 1733 consecutive NSCLC pts from the Lung Cancer Consortium Singapore database, reflex tested for ROS1 rearrangement using break-apart fluorescence in situ hybridization. Clinical data including pts characteristics, concomitant mutations, incidence of brain metastasis, response to chemotherapy or TKIs, were retrospectively analyzed.

      20c51b5f4e9aeb5334c90ff072e6f928 Results

      We identified 34 pts (2.0%) with ROS1 positive NSCLC; median age 52 years (range 28-76), 19 males (55.9%), 26 pts (76.5%) never smoked. A patient with stage I was excluded from outcome analysis. All had adenocarcinoma histology. 8 pts (23.5%) had brain metastases at diagnosis and 6 developed brain metastases during treatment. 6 pts (17.6%) harbored concomitant EGFR mutations; 2 (9.1%) had cMET mutations; 1 had EGFR L858R, cMET and ROS1 alterations simultaneously. 8 of 13 pts (61.5%) had PD-L1>1%. Median overall survival (OS) for all pts was 29.3 months (mths). In the first line, 13 pts received chemotherapy; 11 pemetrexed-based with a response rate (RR) of 78% and 2 gemcitabine-based with a RR of 50%. Progression free survival (PFS) was 9.8 mths and OS was 30.6 mths. Ten pts received ROS1 TKIs (9 crizotinib, 1 entrectinib) as first line with RR 80%, PFS 9.9 mths, and OS 23.7 mths. For second line, 7 pts received chemotherapy, 4 were pemetrexed-based (RR 100%) and 3 were gemcitabine-based (RR 0%), 8 pts received ROS1 TKIs (6 crizotinib, 2 ceritinib) (RR 57%). 3 pts with PD-L1>1% received pembrolizumab without objective response.

      fd69c5cf902969e6fb71d043085ddee6 Conclusions

      ROS1-positive NSCLC has unique clinicopathological characteristics, high rate of brain metastases and concomitant mutations. Despite effective and durable responses to ROS1 TKI and pemetrexed chemotherapy, optimal treatment sequence remains to be explored and the role of immune checkpoint inhibitors is uncertain.

      b651e8a99c4375feb982b7c2cad376e9 Legal entity responsible for the study

      The authors.

      213f68309caaa4ccc14d5f99789640ad Funding

      Has not received any funding.

      682889d0a1d3b50267a69346a750433d Disclosure

      All authors have declared no conflicts of interest.

      cffcb1a185b2d7d5c44e9dc785b6bb25

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    Proffered Paper session II (ID 61)

    • Event: ELCC 2019
    • Type: Proffered Paper session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 4/11/2019, 09:00 - 10:30, Room A
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      109O - Entrectinib in locally advanced or metastatic ROS1 fusion-positive non-small cell lung cancer (NSCLC): Integrated analysis of ALKA-372-001, STARTRK-1 and STARTRK-2 (ID 501)

      09:00 - 10:30  |  Author(s): Daniel Shao Weng Tan

      • Abstract
      • Presentation
      • Slides

      Background

      Entrectinib is a potent ROS1 inhibitor (as well as TRKA/B/C), designed to effectively penetrate the central nervous system (CNS); brain metastases are common in patients (pts) with advanced ROS1 fusion-positive NSCLC. Entrectinib achieves therapeutic levels in the CNS with antitumour activity in multiple intracranial tumour models. We present updated integrated safety and efficacy data from three Phase 1/2 entrectinib studies (ALKA-372-001 [EudraCT 2012-000148-88], STARTRK-1 [NCT02097810], STARTRK-2 [NCT02568267]) in pts with locally advanced/metastatic ROS1 fusion-positive NSCLC.

      a9ded1e5ce5d75814730bb4caaf49419 Methods

      The analysis included pts with ROS1 inhibitor-naïve NSCLC harbouring a ROS1 fusion identified via nucleic acid-based diagnostic platforms. The ROS1 safety-evaluable population included pts who received ≥1 dose of entrectinib; the integrated efficacy analysis included pts with at least 6 months of follow-up. Tumour assessments were done at wk 4 and then every 8 wks by blinded independent central review (BICR), using RECIST v1.1. Primary endpoints by BICR: overall response rate (ORR), duration of response (DOR). Key secondary endpoints: progression-free survival (PFS), safety. Additional endpoints: intracranial ORR (complete/partial response), DOR in pts with intracranial response, PFS in pts with or without baseline CNS disease.

      20c51b5f4e9aeb5334c90ff072e6f928 Results

      In the ROS1 safety-evaluable population (n = 134), at least one treatment-related AE (TRAE) of any grade was seen in 93% of pts. Pts with at least one TRAE by highest grade were: grade 1/2, 59%; grade 3, 31%; grade 4, 4%. There were no grade 5 TRAEs. TRAEs led to dose reduction or discontinuation in 34% and 5% of pts, respectively. Efficacy outcomes are summarised in the table.

      fd69c5cf902969e6fb71d043085ddee6 Conclusions

      Entrectinib is highly active in pts with ROS1 fusion-positive NSCLC, including pts with CNS disease. Entrectinib is well tolerated with a manageable safety profile.

      b651e8a99c4375feb982b7c2cad376e9 Clinical trial identification

      ALKA-372-001 = EudraCT 2012-000148-88 – start date: 2015, trials ongoing STARTRK-1= NCT02097810 – start date: 2014, active, not recruiting (last update 2018) STARTRK-2 = NCT02568267 – start date: 2015, recruiting (last update 2018).

      7a6a3ffa2dadc03a6151ee2c4d6fa383 Editorial acknowledgement

      Medical writing and editorial support provided by Charlotte Kennerley PhD of Gardiner-Caldwell Communications, Ashfield Healthcare Communications and was sponsored by Roche in accordance with Good Publication Practice guidelines.

      934ce5ff971f1ab29e840a35e3ca96e9 Legal entity responsible for the study

      F. Hoffmann-La Roche.

      213f68309caaa4ccc14d5f99789640ad Funding

      Ignyta, Inc., a wholly owned subsidiary of F. Hoffmann-La Roche Ltd.

      682889d0a1d3b50267a69346a750433d Disclosure

      F. Barlesi: Honoraria: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Clovis Oncology, Eli Lilly Oncology, F. Hoffmann–La Roche Ltd, Novartis, Merck, MSD, Pierre Fabre, Pfizer, Takeda. A. Drilon: Advisory boards: Bayer, Ignyta, Loxo Oncology, Pfizer, Roche/Genentech, TP Therapeutics; Research funding: Loxo Oncology. F. De Braud: Advisory boards: Novartis, Roche/Genetech, Merk Serono, Bristol-Myers Squibb, GlaxoSmithKline, BMS, Celgene, Servier, Ignyta, Pfizer, MSD, Philogen, AstraZeneca, Boehringer Ingelheim, Sanofi Aventis, Giscad, Italfarmaco, Eli Lilly, Amgen, Nadirex. S. Siena: Advisory boards: Amgen, Bayer, BMS, CheckmAb, Celgene, Incyte, Merck, Novartis, Roche and Seattle Genetics. M.G. Krebs: Honoraria for Advisory boards: Roche, Janssen, Octimet, Achilles therapeutics; Travel grants: AstraZeneca. C.C. Lin: Honoraria: AstraZeneca, BeiGene, Daiichi Sankyo, Novartis, Roche; Advisory boards: Blueprint, Boehringer Ingelheim, Novartis. T. John: Advisory boards: BMS, AstraZeneca, Boehringer, Takeda, Pfizer, Novartis, Merck, Ignyta, Roche. D.S.W. Tan: Grants and honoraria for Advisory boards: Novartis, Bayer, Boehringer Ingelheim, Merck, AstraZeneca, BMS, Roche, Pfizer and grants from GSK, Novartis, AstraZeneca. T. Seto: Honoraria/research: Astellas, AZ, Bayer, BMS, Chugai, Daiichi Sankyo, Eisai, EliLilly, Kissei, Kyowa HakkoKirin, MerckSerono, Mochida, MSD, Nippon, Novartis, BI, NipponKayakuOno, Pfizer, Roche, Sanofi, ShowaYakuhinKako, Taiho, Takeda, YakultHonsha, Verastem. R. Dziadziuszko: Honoraria, consulting fees: Roche, Pfizer, Boehringer Ingelheim, Clovis Oncology, Novartis, AstraZeneca, Tesaro. H-T. Arkenau: Employee: HCA; Advisory boards: Beigene, Guardant Health, Bicycle. C. Rolfo: Honoraria, Advisory boards: Mylan, Novartis, MSD, GuardantHealth, AstraZeneca. J. Wolf: Corporate sponsored research: BMS, MSD, Novartis, Pfizer; Advisory boards: AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Chugai, Ignyta, Lilly MSD, Novartis, Pfizer, Roche. C. Ye, T. Riehl, S. Eng: Employee: Genentech. R.C. Doebele: Research: Ignyta; Advisory boards; Roche, Ignyta, Takeda, AstraZeneca, Bayer; Stock ownership: Rain Therapeutics; Patent or biological material licensing fees: Ignyta, Abbott Molecular, Rain Therapeutics. All other authors have declared no conflicts of interest.

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