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Lukas Heukamp



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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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      121P - Risk of not receiving second-line therapy is high in EGFR mt+ patients: Real-world data of certified lung cancer centers on treatment sequence in EGFR mt+ patients (ID 316)

      12:30 - 13:00  |  Author(s): Lukas Heukamp

      • Abstract
      • Slides

      Background

      Recently FLAURA study demonstrated significant PFS and numeric OS benefit for Osimertinib 1st line vs. 1st gen. TKI’s Erlotinib/Gefitinib. The number of pts switching from 1st gen. to 3rd gen. TKI (30%) appeared to be low and it is questionable whether these data represent real world sequencing treatment patterns. Therefore, we investigated the sequence pattern, i.e. the percentage of 2nd line therapy in EGFR mt+ pts in 3 certified lung cancer centers in Germany.

      a9ded1e5ce5d75814730bb4caaf49419 Methods

      Data of 912 of 1477 pts tested for EGFR mt+ were analyzed between 2009-2017. 140/144 pts with an activating EGFR mutation (16%) and treated with systemic therapy (4 pts received no therapy) were identified and their treatments were captured as well as their outcome. 36 pts were treated before accessibility to 3rd gen. TKI and 104 pts after accessibility to 3rd gen.TKI.

      20c51b5f4e9aeb5334c90ff072e6f928 Results

      130/140 pts were treated with 1st line TKI and 10 received 1st line chemotherapy. 17 pts are still on 1st line TKI, 8 pts were lost to follow-up, 3 pts died while on 1st line TKI. 112 pts were candidates for 2nd line therapy. 34/112 (30%) of these pts did not receive 2nd line therapy. Causes for not receiving 2nd line therapy were pts refusal (n = 2), bad PS (n = 26) frequently due to CNS metastases, fast progression and death (n = 6). After accessibility of 3rd gen. TKI, 20 of 66 (30%) pts did not receive 2nd line therapy. Median OS of the overall cohort was 27 months (n = 140), median OS of pts receiving 2nd line (n = 78) vs. no 2nd line (n = 62) was 36 vs. 14 months (p < 0.0001). After accessibility of 3rd gen. TKI 30/104 pts (29%) receive a 3rd gen. TKI after 1st line or 2nd line therapy. Median OS of pts receiving (n = 30) and not receiving 3rd gen. TKI (n = 110) was 55 months vs. 22 months (p < 0.0001).

      fd69c5cf902969e6fb71d043085ddee6 Conclusions

      In real world, a significant number of pts treated with 1st or 2nd gen. TKI do not reach 2nd line therapy even when 3rd gen. TKI were accessible. Reasons for not receiving 2nd line therapy are in most cases deterioration of PS and lack of possibility to test for T790M in the minority of cases (n = 28/66, 42% were not tested). These data, although favorable for the small and very selected cohort of pts treated with Osimertinib, might argue for the most effective therapy in 1st line for pts with EGFR mt+ tumors.

      b651e8a99c4375feb982b7c2cad376e9 Legal entity responsible for the study

      F. Griesinger.

      213f68309caaa4ccc14d5f99789640ad Funding

      Has not received any funding.

      682889d0a1d3b50267a69346a750433d Disclosure

      J. Roeper: Honorary: Boehringer Ingelheim, Roche. M. Falk: Honorary: BMS, Boehringer Ingelheim, MSD. L. Heukamp: Advisory board: BMS, Boehringer Ingelheim, Roche, Novartis. F. Griesinger: Advisory boards, travel support: ARIAD, AstraZeneca, Boehringer Ingelheim, BMS, Celgene, Clovis, Lilly, MSD, Novartis, Pfizer, Roche; Scientific support: AstraZeneca, Boehringer Ingelheim, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche. All other authors have declared no conflicts of interest.

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      134P - Mutational spectrum of acquired resistance to reversible versus irreversible EGFR tyrosine kinase inhibitors (ID 297)

      12:30 - 13:00  |  Author(s): Lukas Heukamp

      • Abstract

      Background

      Mutational spectrum of acquired resistance to reversible versus irreversible EGFR tyrosine kinase inhibitors Over the past years, EGFR tyrosine kinase inhibitors (TKI) revolutionized treatment response. 1st-generation (reversible) EGFR TKI later the 2nd –generation irreversible EGFR TKI Afatinib was aimed to improve treatment response. Nevertheless, diverse resistance mechanisms develop within the first year of therapy. Here, we evaluate the prevalence of acquired resistance mechanisms towards reversible and irreversible EGFR TKI.

      a9ded1e5ce5d75814730bb4caaf49419 Methods

      Rebiopsies of patients after progression to EGFR TKI therapy (>6months) were targeted to histological and molecular analysis. Multiplexed targeted sequencing (NGS) was conducted to identify acquired resistance mutations (e.g. EGFR p.T790M). Further, Fluorescence in situ hybridisation (FISH) was applied to investigate the amplification status of bypass mechanisms like, MET or HER2.

      20c51b5f4e9aeb5334c90ff072e6f928 Results

      123 rebiopsy samples of patients that underwent firts-line EGFR TKI therapy ( PFS >6months) were histologically and molecularly profiled upon clinical progression. The EGFR p.T790M mutation ist the major mechanism of acquired resistance in patients treated with reversible as well as irreversible EGFR TKI. Nevertheless a statistically significant difference for the acquisition of T790M mutation has been idientified: 45% of afatinib- vs 65% of reversible EGFR TKI treated patients developed a T790M mutation (p-value 0.02). Progression free survival (PFS) was comparable in patients treated with irreversible EGFR irrespective of the sensitising primary mutation or the acquisition of p.T790M.

      fd69c5cf902969e6fb71d043085ddee6 Conclusions

      The EGFR p.T790M gatekeeper mutation ist he most prominent mechanism of resistance to reversible and irreversible EGFR TKI therapy. Nevertheless there is a statistically significant prevalence of p.T790M acquisition between the two types of TKI, which might be of importance for clinical therapy decision.

      b651e8a99c4375feb982b7c2cad376e9 Legal entity responsible for the study

      The authors.

      213f68309caaa4ccc14d5f99789640ad Funding

      Boehringer Ingelheim.

      682889d0a1d3b50267a69346a750433d Disclosure

      S. Wagener-Ryczek: Honoraria: Boehringer Ingelheim. C. Heydt: Honoraria: AstraZeneca, BMS, Illumina. S. Michels: Honoraria: Novartis, Pfizer, AstraZeneca, Boehringer Ingelheim; Advisory roles: Boehringer Ingelheim, Pfizer; Research funding: Pfizer, Novartis, BMS; Travel support/accommodations: Novartis. J. Fassunke: Honoraria, advisory role: AstraZeneca. M. Tiemann: Honoraria: Pfizer, Novartis, Roche. L. Heukamp: Co-founder: Neo New Oncology. J. Wolf: Honoraria: AstraZeneca, BMS, Clovis Oncology, Lilly, MSD, Novartis, Pfizer, Roche; Advisory roles: AstraZeneca, BMS, Clovis Oncology, Lilly, MSD, Novartis, Pfizer, Roche, Amgen. R. Buettner: Co-founder, Chief Scientific Officer: Targos Molecular Pathology; Honoraria: Roche, Pfizer, Novartis, AstraZeneca, Qiagen, MSD, BMS, Lilly. S. Merkelbach-Bruse: Honoraria: AstraZeneca; Advisory roles: AstraZeneca, Roche. All other authors have declared no conflicts of interest.

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