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Darren Wan-Teck Lim



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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): Darren Wan-Teck Lim

      • 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.

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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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      104O - IMpower150: An exploratory analysis of efficacy outcomes in patients with EGFR mutations (ID 184)

      08:30 - 10:00  |  Author(s): Darren Wan-Teck Lim

      • Abstract
      • Presentation
      • Slides

      Background

      Atezolizumab (atezo; anti–PD-L1) inhibits PD-L1 to restore anticancer immunity; bevacizumab (bev) may enhance atezo efficacy by inhibiting VEGF immunosuppression and promoting T-cell tumour infiltration. Atezo + bev + chemotherapy (chemo) prolonged PFS and OS vs bev + CP in pts with first-line nonsquamous NSCLC in the randomised Ph III IMpower150 study, including pts with EGFR or ALK genomic alterations. The purpose of this analysis is to focus on the efficacy of atezo and/or bev with chemo in pts with EGFR mutations (EGFR-mt).

      a9ded1e5ce5d75814730bb4caaf49419 Methods

      The 1202 enrolled pts received atezo (A) 1200 mg + bev (B) 15 mg/kg + carboplatin (C) AUC 6 + paclitaxel (P) 200 mg/m2 (ABCP) or A + C + P (ACP) or B + C + P (BCP) by IV q3w for 4 or 6 cycles per investigator (INV) decision, then q3w maintenance with atezo + bev, atezo or bev, respectively. Primary endpoints were OS and INV-assessed PFS in the ITT–wild-type population (pts with no EGFR or ALK genomic alterations). Exploratory analyses included OS and INV-assessed PFS in pts with EGFR-mt disease, pts with sensitising EGFR-mt and pts with EGFR-mt disease with prior TKI therapy.

      20c51b5f4e9aeb5334c90ff072e6f928 Results

      These data represent ≥ 20-mo follow-up (data cutoff: 22 Jan 2018) in the ITT population. 124 pts were EGFR-mt; 91 with a sensitising mutation. Baseline characteristics of EGFR-mt pts across treatment arms were generally comparable to the ITT population. OS was improved with ABCP vs BCP in EGFR-mt pts, especially in pts with sensitising EGFR-mts (HR, 0.31 [95% CI: 0.11, 0.83]). This benefit extended to PFS (HR, 0.41 [95% CI: 0.23, 0.75]). See table for full efficacy results. Safety was similar between the EGFR-mt and ITT populations.

      fd69c5cf902969e6fb71d043085ddee6 Conclusions

      IMpower150 is the first randomised Ph III trial of a checkpoint inhibitor to show a benefit in pretreated EGFR-mt pts. Adding atezo to standard-of-care bev and chemo provided survival benefit in EGFR-mt pts who have failed TKIs, for whom this regimen may represent a new treatment option.

      b651e8a99c4375feb982b7c2cad376e9 Clinical trial identification

      NCT02366143.

      7a6a3ffa2dadc03a6151ee2c4d6fa383 Editorial acknowledgement

      Medical writing assistance for this abstract was provided by Jessica Men, PharmD, of Health Interactions and funded by F. Hoffmann-La Roche, Ltd.

      934ce5ff971f1ab29e840a35e3ca96e9 Legal entity responsible for the study

      F. Hoffmann-La Roche, Ltd.

      213f68309caaa4ccc14d5f99789640ad Funding

      F. Hoffmann-La Roche, Ltd.

      682889d0a1d3b50267a69346a750433d Disclosure

      M. Reck: Speakers bureau, consulting, advisory role: Roche, Lilly, Pfizer, BI, AZ, MSD, BMS, Merck, Novartis, Celgene; Other (support of parent study, funding of editorial support): Roche. R. Jotte: Speakers bureau; travel, accommodations, expenses: Bristol-Myers Squibb; Other (support of parent study, funding of editorial support): Roche. T.S.K. Mok: Honoraria, consult/ad role, research: AZ, BI, BMS, Merck, NVS, Pfizer, Roche/GNE; Honoraria, consult/ad role: LLY; Consult/Ad Role: ACEA, Celgene, geneD, Ignyta, OGXI, Vertex; Consult/ad role, research: Clovis, SFJ; Research: Eisai, Taiho; Stock: Sanomics, Hutch. D.W-T. Lim: Honoraria: AZ, BI, Novartis, MSD, Pfizer, Roche, Takeda, Taiho; Research grants (institution): BMS; Stock: Clearbridge Biomedics Pte Ltd, Mesh Bio Pte Ltd; Other (support of parent study, funding of editorial support): Roche. F. Cappuzzo: Speakers/Advisory board: Roche, AZ, BMS, Pfizer, MSD, Takeda; Other (support of parent study, funding of editorial support): Roche. F. Orlandi: Consult/ad role: AZ, Lilly; Consult/ad role, travel, research: Roche, BMS, MSD; Consult/ad role, travel: Pfizer; Speaker, travel, research: MedImm; Research: Amgen, BI, Astellas, Celltrion. D. Stroyakovskiy, C.A. Thomas: Support of parent study, funding of editorial support: Roche. N. Nogami: Honoraria: AZ, Pfizer, Ono Pharmaceutical, Kyowa Hakko Kririn, Taiho, Chugai, Eli Lilly, BI, MSD; Other (support of parent study and funding of editorial support): Roche. D. Rodríguez-Abreu: Speakers bureau: MSD, Roche, BMS, AZ, Pfizer; Other (support of parent study and funding of editorial support): Roche. D. Moro-Sibilot: Honoraria; Consulting/advisory role, travel, accommodations, expenses: Roche, MSD, Pfizer, BMS, AZ; Honoraria, consulting/advisory role: Novartis, Lilly; Other (support of parent study, funding of editorial support): Roche. F. Barlesi: Support of parent study, funding of editorial support: Roche; Personal fees: AZ, BMS, BI, Clovis, Lilly, Roche, Novartis, Merck, MSD, Pierre Fabre, Pfizer, Takeda; Consulting/advisory: MSD, Takeda. G. Finley: Speakers: BMS, BI, Astellas Medivation, Merck; Support of parent study, funding of editorial support: Roche. M. Nishio: Speakers/Ad board, research grant: Ono Pharma, BMS, Pfizer, Chugai, Lilly, Taiho, AZ, MSD, Novartis; Speakers/Ad board: BI, Sankyo, Merck; Research Grant: Astellas; Support of parent study, funding of editorial support: Roche. A. Lee: Employee/Stock: Genentech; Support of parent study, funding of editorial support: Roche. G. Shankar, W. Yu: Employee: Genentech; Support of parent study, funding of editorial support: Roche. M.A. Socinski: Honoraria/speakers bureau/research funding: Genentech; Support of parent study, funding of editorial support: Roche.

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