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Alastair Greystoke



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    Lunch & Poster Display session (ID 58)

    • Event: ELCC 2019
    • Type: Poster Display session
    • Track:
    • Presentations: 2
    • Moderators:
    • Coordinates: 4/11/2019, 12:30 - 13:00, Hall 1
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      140P - Brigatinib experience on the ALK project (ID 576)

      12:30 - 13:00  |  Author(s): Alastair Greystoke

      • Abstract

      Background

      The ALK Project established a network across the UK with the aim to analyse treatment patterns/outcomes and promote collaborations and research. The treatment pathway for ALK+ patients has been revolutionised in recent years.

      a9ded1e5ce5d75814730bb4caaf49419 Methods

      A multicentre retrospective analysis across 32 NHS hospitals/trusts identified 196 ALK+ non-small cell lung cancer (NSCLC) patients who were offered treatment by Dec-2018. Patients who received brigatinib during their treatment pathway were selected. The primary aims were 2-years overall survival (OS) and median OS from start of brigatinib. The secondary aims were objective response rate (ORR), incidence of grade 3-4 toxicity and 5-years/median OS from diagnosis of advanced NSCLC.

      20c51b5f4e9aeb5334c90ff072e6f928 Results

      A total of 50 patients were included with 48% being males, 70% never smoked tobacco and the median age at diagnosis was 50 years. 66% of patients developed brain metastasis at some point during their care and 52% had brain metastasis at the start of brigatinib. Brigatinib was used as the first, second or subsequent ALK inhibitor in 18%, 50% and 32% of cases, respectively. 82% of patients were exposed to other ALK inhibitors during their treatment pathway and 46% received chemotherapy prior to the start of any ALK inhibitor. On a median follow-up (since start of brigatinib) of 10 months, patients stayed on brigatinib for a median of 9 months (95% CI, 3.1-14.9), reaching 14 months (95%CI 11.0-19.9) if no brain metastasis (p = 0.15). The overall ORR was 64% and the incidence of grade 3-4 toxicity was 16%. Median OS from start of brigatinib was not reached and the 2-years OS according to brain metastasis was 61% or 83%, in favour of those without brain metastasis (p = 0.037). The median OS from diagnosis of advanced NSCLC was not reached and the 5-years OS was 55%.

      fd69c5cf902969e6fb71d043085ddee6 Conclusions

      Brigatinib is well tolerated and an effective treatment even in heavily pre-treated patients or in those with brain metastasis. A nationwide collaboration is possible and revealed the remarkable survival improvements for ALK+ patients with the development of newer generations of ALK inhibitors.

      b651e8a99c4375feb982b7c2cad376e9 Legal entity responsible for the study

      The Christie NHS Foundation Trust.

      213f68309caaa4ccc14d5f99789640ad Funding

      Has not received any funding.

      682889d0a1d3b50267a69346a750433d Disclosure

      All authors have declared no conflicts of interest.

      cffcb1a185b2d7d5c44e9dc785b6bb25

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      98P - Implications for UK practice of the use of durvalumab in stage III NSCLC (ID 559)

      12:30 - 13:00  |  Author(s): Alastair Greystoke

      • Abstract

      Background

      The PACIFIC trial showed a survival benefit in patients receiving Durvalumab after concurrent chemoradiotherapy (CRT) in stage III Non-Small Cell Lung Cancer (NSCLC). Key inclusion criteria were platinum doublet chemotherapy with no chemotherapy delivered after concurrent phase. Dose delivered was 54 - 66Gy and treatment started within 42 days of completing radiotherapy. European licence is restricted to patients with PDL1 positive tumours. Previous UK audits have shown a number of CRT regimens in routine use. We assessed the implications to UK practice of adding durvalumab after CRT.

      a9ded1e5ce5d75814730bb4caaf49419 Methods

      A 9 point questionnaire was sent by email to all 50 radiotherapy centres delivering chemoradiotherapy for NSCLC in the UK.

      20c51b5f4e9aeb5334c90ff072e6f928 Results

      21 responses were received (42%) at the time of submission. Rates of concurrent treatment ranged from 10 - 90% (median 40%, IQR 25-60%) with median surgery rates for N2 disease of 10%. Doses delivered ranged from 55 to 66 Gy (median 60, IQR 55 – 64 Gy) in a median of 30 fractions (IQR 20 to 32). 10 centres used hypofractionated regimens. The most common chemotherapy back-bone was cisplatin and vinorelbine (1 centre used carboplatin and 1 etoposide routinely). 11 centres prescribe chemotherapy post concurrent treatment. Currently only 3 centres scan within the 6 week window after completion of treatment. The majority of centres are now planning to avoid giving consolidative chemo after concurrent CRT and will scan early after CRT. 13 centres are already testing PDL1 in this context. Durvalumb will be supervised in 16 centres by a clinical oncologist, in 2 by medical oncologist with the remaining 3 undecided.

      fd69c5cf902969e6fb71d043085ddee6 Conclusions

      The implementation of consolidative Durvalumab in stage III NSCLC post concurrent CRT will require changes in practice in the majority of UK centres. Most centres have already implemented some changes but more work needs to be done to standardise practice and ensure equality of access for patients.

      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 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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      105O - Osimertinib for patients (pts) with leptomeningeal metastases (LM) associated with EGFRm advanced NSCLC: The AURA LM study (ID 178)

      08:30 - 10:00  |  Author(s): Alastair Greystoke

      • Abstract
      • Presentation
      • Slides

      Background

      Osimertinib, a 3rd-generation EGFR-TKI selective for both sensitising and EGFR T790M resistance mutations, has shown efficacy in pts with CNS metastases; encouraging activity has been reported in pts with LM at 160 mg once daily (QD) (BLOOM; NCT02228369). We report LM activity with osimertinib 80 mg QD in pts with LM from studies across the AURA program (NCT01802632; NCT02094261; NCT02442349; NCT02151981).

      a9ded1e5ce5d75814730bb4caaf49419 Methods

      Pts with EGFR T790M positive advanced NSCLC and progression on EGFR-TKI received osimertinib 80 mg QD. Patients with LM and CNS metastases were eligible if asymptomatic and stable. Baseline brain scans were mandated in pts with known or treated CNS metastases at study entry; pts with evidence of LM by neuroradiological blinded independent review (BICR) were included for retrospective analysis. Follow-up brain scans were assessed for radiologic LM response by LM BICR per Response Assessment in Neuro-Oncology LM criteria. LM objective response rate (ORR), LM duration of response (DoR), LM progression-free survival (PFS) and overall survival (OS) were assessed retrospectively. Results are based on individual data cutoffs for each study. A longitudinal analysis overlaid changes from baseline non-CNS tumour size with LM responses at each visit for AURA LM and BLOOM LM pts.

      20c51b5f4e9aeb5334c90ff072e6f928 Results

      22 LM pts from the AURA studies were included for analysis. Median treatment exposure was 7.3 mo (range 2.3–16.5). Baseline characteristics were broadly consistent with the overall AURA study population: median age 58 yrs; female 59%; Asian 82%; WHO PS 1 82%. LM ORR was 55% (95% CI 32, 76); complete or partial LM response reported in 6 pts (27%) each. Median LM DoR was not reached (95% CI 2.8, not calculable [NC]). Median LM PFS was 11.1 mo (95% CI 4.6, NC). OS was 18.8 mo (95% CI 6.3, NC). Graphical assessment of longitudinal analysis showed similar non-CNS and LM responses in AURA LM and BLOOM LM pts.

      fd69c5cf902969e6fb71d043085ddee6 Conclusions

      Consistent with early efficacy outputs from BLOOM (160mg QD), osimertinib 80 mg QD showed a clinically meaningful benefit in pts with T790M-positive NSCLC and radiographically-detected LM. Additional studies are needed to further evaluate the CNS efficacy of osimertinib 80 mg QD in pts with EGFRm NSCLC and LM.

      b651e8a99c4375feb982b7c2cad376e9 Clinical trial identification

      AURA extension (NCT01802632), AURA2 (NCT02094261), AURA3 (NCT02151981), AURA17 (NCT02442349).

      7a6a3ffa2dadc03a6151ee2c4d6fa383 Editorial acknowledgement

      Medical support was provided by Robert Harrison, PhD, of iMed Comms, Macclesfield, UK, an Ashfield Company, part of UDG Healthcare plc, and funded by AstraZeneca, Cambridge, UK, in accordance with Good Publications Practice (GPP3) guidelines.

      934ce5ff971f1ab29e840a35e3ca96e9 Legal entity responsible for the study

      AstraZeneca.

      213f68309caaa4ccc14d5f99789640ad Funding

      AstraZeneca.

      682889d0a1d3b50267a69346a750433d Disclosure

      M-J. Ahn: Speakers’ bureau: AstraZeneca, MSD, ONO, Lilly, Roche; Consultant: Alpha Pharmaceutical. C-H. Chiu: Honorarium: AZ, BI, Novartis, Pfizer, Roche. J-Y. Han: Honoraria: Roche, AstraZeneca, BMS, MSD; Advisory role: AstraZeneca, BMS, MSD, Lilly, Novartis, Pfizer; Research fund: Roche, Pfizer, ONO. S.B. Goldberg: Research support: AstraZeneca; Advisory board member: AstraZeneca, Boehringer Ingelheim, Eli Lilly, Bristol-Myers Squibb, Genentech, Amgen, Spectrum. A. Greystoke: Consultancy fees, speaker fees: AstraZeneca. J. Crawford: Scientific advisor: Amgen, Enzychem, Merck, Pfizer; Consultant: Amgen, AstraZeneca, Coherus, Enzychem, Merck, Pfizer; Research support: AstraZeneca, Genentech, Helsinn; Chair/DSMB member: Beyond Spring, G1 Therapeutics, Janssen, Merrimack, Mylan, Roche. X. Huang, M. Johnson, K. Vishwanathan, A. Mendoza-Naranjo: Employee, shareholder: AstraZeneca. T.S.K. Mok: Leadership (for-profit): ChiMed, Sanomics Ltd.; Leadership (non-profit): IASLC, ASCO, Chinese Society of Clinical Oncology; Shareholder: Sanomics Ltd.; Honoraria: AZ, BI, Roche/Genentech, Pfizer, Lilly, Merck Serono, MSD, Novartis, SFJ, ACEA, Vertex, BMS, Oncogenex, Celgene, Ignyta, Cirina, Fishawack Facilitate, Takeda Oncology, Janssen, ChiMed; Consulting/advisory role: AZ, BI, Roche/Genentech, Pfizer, Lilly, Merck Serono, MSD, Novartis, SFJ Company, ACEA, Vertex, BMS, GeneDecode, Oncogenex, Celgene, Ignyta, Cirina, Fishawack Facilitate, Janssen, Takeda Oncolog, ChiMed; Research funding: AZ, BI, Pfizer, Novartis, SFJ, Roche, MSD, Clovis Oncology, BMS, Eisai, Taiho, Merck Serono, XCovery. All other authors have declared no conflicts of interest.

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