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Dong-Wan Kim



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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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      122P - Osimertinib as first-line (1L) treatment for epidermal growth factor receptor (EGFR) mutation-positive advanced non-small cell lung cancer (NSCLC): Final efficacy and safety results from two phase I expansion cohorts (ID 404)

      12:30 - 13:00  |  Author(s): Dong-Wan Kim

      • Abstract
      • Slides

      Background

      Osimertinib is a 3rd-generation, CNS-active EGFR-tyrosine kinase inhibitor (TKI) that potently and selectively inhibits both EGFR-TKI sensitising (EGFRm) and EGFR T790M resistance mutations. Earlier results from the Ph I AURA (NCT01802632) and Ph III FLAURA (NCT02296125) studies have established 1L osimertinib efficacy. We report final efficacy and safety data from two Ph I expansion cohorts who received 1L osimertinib 80 or 160 mg for advanced EGFRm NSCLC in AURA.

      a9ded1e5ce5d75814730bb4caaf49419 Methods

      Treatment-naïve pts with locally advanced/metastatic EGFRm NSCLC received osimertinib 80 or 160 mg once daily. Endpoints included objective response rate (ORR), progression-free survival (PFS) and safety evaluation. EGFRm status was confirmed via local and/or central laboratory testing. Key eligibility criteria included measurable disease and WHO performance status 0/1. Pts with stable asymptomatic CNS metastases were eligible. Data cutoff: 1 May 2018.

      20c51b5f4e9aeb5334c90ff072e6f928 Results

      Overall, 60 patients (pts) were enrolled at two doses (80 mg, n = 30; 160 mg, n = 30): 75% female; 72% Asian; 43% with EGFR ex19del; 48% with L858R. Five pts were EGFR T790M mutation-positive by central test at study entry. Median follow up: 19.1 mo. ORR (95% CI): 67% (47, 83) in the 80 mg cohort, 87% (69, 96) in the 160 mg cohort, 77% (64, 87) overall. Median duration of response (95% CI): 19.3 mo (12.2, 24.7) in the 80 mg cohort, 16.7 mo (9.7, 29.0) in the 160 mg cohort, 18.0 mo (12.5, 24.7) overall. Median PFS (95% CI): 22.1 mo (12.3, 30.2) in the 80 mg cohort, 19.3 mo (11.1, 26.0) in the 160 mg cohort, 20.5 mo (13.7, 26.1) overall (78% maturity). 42% (95% CI 29, 54) and 14% (95% CI 6, 26) of pts were progression free at 24 and 48 mo, respectively. Dose reductions occurred in 27% and 60% of pts at 80 mg and 160 mg, respectively. Most common adverse events overall: (% [Grade ≥3]) diarrhoea (80 mg, 63% [3%]; 160 mg, 87% [7%]), stomatitis (80 mg, 47% [0]; 160 mg, 53% [3%]), paronychia (80 mg, 37% [0]; 160 mg, 57% [10%]).

      fd69c5cf902969e6fb71d043085ddee6 Conclusions

      Consistent with previously reported results, 1L osimertinib for EGFRm advanced NSCLC results in prolonged PFS at both doses and better tolerability at the 80 mg dose.

      b651e8a99c4375feb982b7c2cad376e9 Clinical trial identification

      NCT01802632 (25 February 2013).

      7a6a3ffa2dadc03a6151ee2c4d6fa383 Editorial acknowledgement

      Medical writing support was provided by Natasha Cary BSc, from iMed Comms, an Ashfield Company and funded by AstraZeneca.

      934ce5ff971f1ab29e840a35e3ca96e9 Legal entity responsible for the study

      AstraZeneca.

      213f68309caaa4ccc14d5f99789640ad Funding

      AstraZeneca.

      682889d0a1d3b50267a69346a750433d Disclosure

      J.C-H. Yang: Honoraria: BI, Roche, MSD, AstraZeneca, Novartis; Consulting/advisory: BI, Novartis, AstraZeneca, Roche/Genentech, Clovis Oncology, Lilly, MSD, Merck Serono, Celgene, Astellas Pharma, Bayer, Pfizer, Ono Pharmaceutical, Bristol-Myers Squibb, Yuhan, Hansoh. S.S. Ramalingam: Advisory boards: AbbVie, Amgen, AstraZeneca, BMS, Celgene, Genentech, Lilly, Merck, Roche, Nektar, Loxo, Takeda; Research grants: Merck, Tesaro. C.K. Lee: Advisory boards: AstraZeneca, Roche, Norvatis, Pfizer. Research funding to institution: AstraZeneca for the trials in which I am currently involved. T. Kurata: Research grants: AstraZeneca, MSD; Honoraria: AstraZeneca, MSD, Ono, Bristol-Myers Squibb, Chugai, Eli Lilly. D-W. Kim: Advisory board membership, personal expenses: Novartis. T. John: Consultancy: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Takeda, Pfizer, Novartis, Merck, Roche. N. Nogami: Honoraria: AstraZeneca, Chugai Pharmaceutical, Eli Lilly Japan K.K., MSD, ONO Pharmaceutical, Pfizer Japan Inc., Taiho Pharmaceutical. Y. Ohe: Honoraria, consulting, research funding: AstraZeneca, Chugai, Dainippon Lilly, Ono, BMS Japan, Daiichi Sankyo, BI, Bayer, Ignyta, Pfizer, MSD, Taiho, Novartis, Kyorin, Kyowa Hakko Kirin, Takeda, Celltrion. Y. Rukazenkov: Employee and shareholder: AstraZeneca. P.A. Jänne: Consultancy: AstraZeneca, BI, Pfizer, Merrimack, Roche/Genentech, Chugai, AceaBiosciences, ARIAD Pharma, Ignyta, LOXO Oncology; Stock ownership: Gatekeeper Pharma; Research funding: Astellas, AstraZeneca; IP: EGFR mutations licensed to Lab Corp. All other authors have declared no conflicts of interest.

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    Proffered Paper session III (ID 64)

    • Event: ELCC 2019
    • Type: Proffered Paper session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 4/12/2019, 08:30 - 10:00, Room A
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      107O - Crizotinib in advanced ROS1-rearranged non-small cell lung cancer (NSCLC): Overall survival (OS) and updated safety from PROFILE 1001 (ID 197)

      08:30 - 10:00  |  Author(s): Dong-Wan Kim

      • Abstract
      • Presentation
      • Slides

      Background

      In the ongoing phase 1 PROFILE 1001 study (NCT00585195), crizotinib provided a meaningful clinical benefit for patients (pts) with advanced ROS1-rearranged NSCLC, as evidenced by a high objective response rate (72%) and rapid, substantial and durable responses (median duration of response, 18 months [mo]); in addition, crizotinib was well-tolerated (Shaw, N Engl J Med, 2014). Here, we present OS results and updated safety (additional follow-up >3 years) in these pts.

      a9ded1e5ce5d75814730bb4caaf49419 Methods

      Pts with histologically confirmed NSCLC containing ROS1 rearrangements were enrolled and treated with oral crizotinib 250 mg twice daily (BID). ROS1 status was assessed by fluorescence in situ hybridization or reverse transcriptase polymerase chain reaction.

      20c51b5f4e9aeb5334c90ff072e6f928 Results

      Between October 2010 and June 2018, 53 pts with ROS1-rearranged NSCLC were treated with crizotinib; median duration of treatment was 22 mo (95% confidence interval [CI]: 15, 36). At the time of data cutoff (June 30, 2018), 12 pts (22.6%) remained on treatment. A total of 26 deaths (49.1%) occurred over a median follow-up period of 63 mo. Median OS was 51 mo (95% CI: 29, not reached) and the probabilities of survival at 12, 24 and 48 mo were 78.8%, 67.0% and 50.7%, respectively. With a median treatment duration nearly 8 mo longer than that for the primary endpoint analysis and 30.2% of patients on treatment for more than 4 years, no new safety signals were noted. The most common grade 3 treatment-related adverse events (TRAEs; in ≥ 5% of pts) were hypophosphatemia (15.1%) and neutropenia (9.4%); no grade 4 TRAEs or treatment-related deaths were reported. With longer follow-up, there were no permanent discontinuations associated with TRAEs.

      fd69c5cf902969e6fb71d043085ddee6 Conclusions

      The results of the OS analysis and updated safety information from PROFILE 1001 continue to support the favorable benefit/risk profile of crizotinib 250 mg BID for the treatment of patients with advanced ROS1-positive NSCLC.

      b651e8a99c4375feb982b7c2cad376e9 Clinical trial identification

      NCT00585195.

      7a6a3ffa2dadc03a6151ee2c4d6fa383 Editorial acknowledgement

      Editorial assistance was provided by Vasupradha Vethantham, PhD, of inScience Communications, Springer Healthcare (New York, NY, USA), with funding from Pfizer, Inc.

      934ce5ff971f1ab29e840a35e3ca96e9 Legal entity responsible for the study

      Pfizer, Inc.

      213f68309caaa4ccc14d5f99789640ad Funding

      Pfizer, Inc.

      682889d0a1d3b50267a69346a750433d Disclosure

      A. Shaw: Fees for consulting/advisory board roles: ARIAD/Takeda, Blueprint Medicines, Daiichi Sankyo, EMD Serono, Foundation Medicine Genentech, Ignyta, KSQ Therapeutics, Loxo, Novartis, Pfizer, Roche, Taiho; Honoraria: Novartis, Pfizer, Roche; Research funding to institution: Daiichi Sankyo, Ignyta, Novartis, Pfizer, Roche/Genentech, TP Therapeutics. Y-J. Bang: Advisory boards: Astellas, AstraZeneca, Bayer, BeiGene, Bristol-Myers Squibb, Daiich-Sankyo, Eli Lilly, GreenCross, Genentech/Roche, Hanmi, Novartis,  Merck Serano,  MSD, Samyang Biopharm, Taiho; Research funding to institution: Astellas, AstraZeneca, Bayer, BeiGene, Bristol-Myers Squibb, Boeringer Ingelheim, Boston Biomedical, CKD Pharma, Curis, Daiichi Sankyo, Eli Lilly, FivePrime, Glaxo Smith-Kline, Genentech/Roche, Green Cross, MacroGenics, Merck Serano, MSD, Novartis, Pfizer, Ono, Takeda, Taiho. D.R. Camidge: Advisory boards: AbbVie, ARIAD, Array, Celgene, Clovis, Eli Lilly, G1 Therapeutics (DSMB), Genoptix, Ignyta, Mersana Therapeutics, Novartis, Orion, Roche/Genentech, Takeda; Research for investigator-initiated trials: ARIAD, Takeda. G.J. Riely: Funding to institution: Pfizer for the conduct of this research; Research support to institution: Novartis, Roche, Takeda. Compensated consultant: Genentech/Roche. G.I. Shapiro: Research funding to the Dana-Farber Cancer Institute: Pfizer for the conduct of the study; Advisory boards: Eli Lilly, G1 Therapeutics, Merck/EMD Serono, Roche, Pfizer, Vertex Pharmaceuticals. T. Usari, S.C. Wang, K. Wilner: Employee, holds stock: Pfizer. J.W. Clark: Institutional research funding: Pfizer. S-H.I. Ou: Fees for consulting/Advisory board: Pfizer; Research funding to institution: Eli Lilly, Merck/EMD Serono, Pfizer. All other authors have declared no conflicts of interest.

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