Author of

• 28971

  +

  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

  • 29055

    +

    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): Frank Griesinger
    • Abstract
    • Slides

    Background
    

    Recently FLAURA study demonstrated significant PFS and numeric OS benefit for Osimertinib 1^st line vs. 1^st gen. TKI’s Erlotinib/Gefitinib. The number of pts switching from 1^st gen. to 3^rd 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 2^nd 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 3^rd gen. TKI and 104 pts after accessibility to 3^rd gen.TKI.

    20c51b5f4e9aeb5334c90ff072e6f928 Results
    

    130/140 pts were treated with 1^st line TKI and 10 received 1^st line chemotherapy. 17 pts are still on 1^st line TKI, 8 pts were lost to follow-up, 3 pts died while on 1^st line TKI. 112 pts were candidates for 2^nd line therapy. 34/112 (30%) of these pts did not receive 2^nd line therapy. Causes for not receiving 2^nd 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 3^rd gen. TKI, 20 of 66 (30%) pts did not receive 2^nd line therapy. Median OS of the overall cohort was 27 months (n = 140), median OS of pts receiving 2^nd line (n = 78) vs. no 2^nd line (n = 62) was 36 vs. 14 months (p < 0.0001). After accessibility of 3^rd gen. TKI 30/104 pts (29%) receive a 3^rd gen. TKI after 1^st line or 2^nd 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 1^st or 2^nd gen. TKI do not reach 2^nd line therapy even when 3^rd gen. TKI were accessible. Reasons for not receiving 2^nd 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 1^st 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.

    cffcb1a185b2d7d5c44e9dc785b6bb25

    Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • 29116

    +

    182TiP - A phase II trial of tepotinib in patients with non-small cell lung cancer (NSCLC) harboring MET alterations: The VISION study (ID 452)

    12:30 - 13:00  |  Author(s): Frank Griesinger
    • Abstract
    • Slides

    Background
    

    Dysregulation of the MET pathway is common in human carcinomas and leads to dependency on MET signalling, representing a potential therapeutic target in NSCLC. MET alterations including MET-exon 14 skipping mutations (METex14) and MET amplification (METamp) are known oncogenic drivers, and occur in 3–4% and 0.4–1.5% of NSCLCs, respectively. Tepotinib, a potent selective, small molecule MET inhibitor, has shown promise in preclinical and phase 1 trials.

    a9ded1e5ce5d75814730bb4caaf49419 Trial design
    

    VISION (NCT02864992), a single-arm, open-label, multicentre Phase 2 trial, will assess the antitumour activity and tolerability of tepotinib 500 mg daily, as 1^st–3^rd line of treatment, in patients with histologically-confirmed, advanced (stage IIIB/IV) NSCLC (all histologies) harboring MET alterations. Patients with METex14 + (determined by tumor biopsy [TBx] and/or plasma ‘liquid’ biopsy [LBx]; Cohort A) or METamp (determined by LBx; Cohort B) NSCLC are included. Prior treatment with checkpoint inhibitors is permitted. Patients with epidermal growth factor receptor-activating mutations, anaplastic lymphoma kinase rearrangements, or with brain metastasis as the only measurable lesion are excluded. The primary endpoint is objective response rate (ORR) by independent review committee via Response Evaluation Criteria in Solid Tumors v1.1. Secondary objectives include investigator-assessed ORR, duration of response, disease control, progression free survival, overall survival, tolerability, and safety. Adverse events (AEs) will be monitored throughout the study and for 30 days (90 days for serious AEs) after treatment and graded per National Cancer Institute Common Terminology Criteria for Adverse Events v4.0. Enrolment into Cohort A commenced in September 2016 and is continuing. Enrolment of patients with LBx-confirmed METamp into Cohort B commenced in September 2018; based on an interim analysis of 12 patients, recruitment may continue to enrol ≥60 patients. This abstract was previously presented at ESMO Asia 2018, FPN 546TiP, Paik et al. Reused with permission.

    d9b324a48b043b3d87bc9b3fe620f260 Clinical trial identification
    

    NCT02864992.

    7a6a3ffa2dadc03a6151ee2c4d6fa383 Editorial acknowledgement
    

    Medical writing assistance (funded by Merck KGaA, Darmstadt, Germany) was provided by Lisa Jolly, Bioscript Science (Macclesfield, UK).

    934ce5ff971f1ab29e840a35e3ca96e9 Legal entity responsible for the study
    

    Merck KGaA.

    213f68309caaa4ccc14d5f99789640ad Funding
    

    Merck KGaA.

    682889d0a1d3b50267a69346a750433d Disclosure
    

    P. Paik: Advisory board, honorarium: Celgene; IDMC: Takeda. A. Cortot: Advisory boards member: AstraZeneca, BMS, MSD, Pfizer, Novartis, Roche, Takeda, Boehringer Ingelheim; Corporate-sponsored research: Merck. E. Felip: Speaker’s bureau, advisory board: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celegene, Eli Lilly, Guardant Health, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Takeda, AbbVie, Merck. J. Mazieres: Advisory board: Roche, BMS, MSD, AstraZeneca, Pfizer, Novartis. F. Griesinger: Scientific support: ASTRA, Boehringer Ingelheim, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, Takeda, Siemens; Talks, presentations, advisory boards: ASTRA, Boehringer Ingelheim, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, Takeda, ARIAD, AbbVie, Siemens. R. Bruns, J. Scheele, J. Straub: Employee: Merck KGaA, Darmstadt, Germany. R. Veillon: Congress registration, advisory board: Boehringer Ingelheim, Bristol-Myers Squibb, Merck Sharp & Dohme, Roche, Pfizer, AbbVie, Merck. All other authors have declared no conflicts of interest.

    cffcb1a185b2d7d5c44e9dc785b6bb25

    Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

• 29178

  +

  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

  • 29180

    +

    106O - Brigatinib (BRG) vs crizotinib (CRZ) in the phase III ALTA-1L trial (ID 166)

    08:30 - 10:00  |  Author(s): Frank Griesinger
    • Abstract
    • Presentation
    • Slides

    Background
    

    We report results of the first interim analysis (IA) from the ALTA-1L study of BRG vs CRZ in anaplastic lymphoma kinase (ALK) inhibitor–naive, ALK-positive non–small cell lung cancer (ALK+ NSCLC; NCT02737501).

    a9ded1e5ce5d75814730bb4caaf49419 Methods
    

    This open-label, multicenter study enrolled patients (pts) with advanced ALK+ NSCLC. Eligible pts had ≤1 prior systemic therapy for advanced NSCLC. Asymptomatic central nervous system (CNS) metastases were allowed. Pts were randomized 1:1 to BRG 180 mg QD with 7-day lead-in at 90 mg or CRZ 250 mg BID. Primary endpoint was blinded independent review committee (BIRC)-assessed progression-free survival (PFS; RECIST v1.1); secondary efficacy endpoints included BIRC-assessed objective response rate (ORR), intracranial ORR (iORR), and intracranial PFS (iPFS). IAs were planned at 50% and 75% of 198 expected PFS events.

    20c51b5f4e9aeb5334c90ff072e6f928 Results
    

    275 pts were randomized (BRG/CRZ, n = 137/138); median age (years) 58/60. 26%/27% received prior chemotherapy for advanced disease, and 29%/30% had baseline brain metastases. At data cutoff (19 Feb 2018), with a median follow-up of 11.0/9.3 months (BRG/CRZ) and 99 PFS events, BRG met the prespecified threshold for statistical superiority vs CRZ in the primary endpoint of BIRC-assessed PFS (HR 0.49; 95% CI, 0.33–0.74; log-rank P = 0.0007); BRG median PFS was not reached (NR; 95% CI, NR) vs CRZ 9.8 months (95% CI, 9.0–12.9). Investigator-assessed PFS HR 0.45 (95% CI, 0.30–0.68); log-rank P = 0.0001. Table shows additional efficacy data. Most common grade ≥3 treatment-emergent adverse events (AEs): BRG: increased blood creatine phosphokinase (16.2%) and lipase (13.2%), hypertension (9.6%); CRZ: increased alanine aminotransferase (9.5%), aspartate aminotransferase (5.8%), and lipase (5.1%). Any grade interstitial lung disease/pneumonitis: BRG, 3.7%; CRZ, 2.2%. Discontinuations due to AE (BRG/CRZ): 11.8%/8.8%.

    fd69c5cf902969e6fb71d043085ddee6 Conclusions
    

    BRG showed a statistically and clinically significant improvement in PFS vs CRZ in ALK inhibitor–naive ALK+ NSCLC.

    b651e8a99c4375feb982b7c2cad376e9 Clinical trial identification
    

    NCT02737501.

    7a6a3ffa2dadc03a6151ee2c4d6fa383 Editorial acknowledgement
    

    Professional medical writing assistance was provided by Lauren Gallagher, PhD, (Peloton Advantage, Parsippany, NJ) and funded by Millennium Pharmaceuticals, Inc.

    934ce5ff971f1ab29e840a35e3ca96e9 Legal entity responsible for the study
    

    ARIAD Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.

    213f68309caaa4ccc14d5f99789640ad Funding
    

    ARIAD Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.

    682889d0a1d3b50267a69346a750433d Disclosure
    

    R. Califano: Honoraria, consulting/advisory role: AstraZeneca, BMS, Roche, MSD, Boehringer Ingelheim, Takeda, Novartis, Pfizer, Lilly Oncology. C. Gridelli: Speakers bureau, advisory role: Pfizer, Roche. A. Delmonte: Consulting/advisory role: AstraZeneca, Boehringer Ingelheim. M.R. Garcia Campelo: Honoraria: ARIAD, AstraZeneca, Roche, Pfizer, BMS, Boehringer Ingelheim; Speakers bureau, advisory role: ARIAD, AstraZeneca, Roche, Pfizer, BMS, Boehringer Ingelheim. A. Bearz: Speakers bureau, advisory role: AstraZeneca, Pfizer, Eli Lilly, BMS, Novartis, Roche, MSD, Boehringer Ingelheim, Takeda. F. Griesinger: Research funding to institution: AstraZeneca, Boehringer Ingelheim, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, Takeda, Siemens; Consulting or advisory role: ARIAD, AstraZeneca, Boehringer Ingelheim, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, Takeda, ARIAD, AbbVie, Siemens. E. Felip: Consulting/advisory role: AbbVie, AstraZeneca, Blue Print Medicines, Boehringer Ingelheim, BMS, Celgene, Eli Lilly, Guardant Health, Janssen, Merck KGaA, MSD, Novartis, Pfizer, Roche, Takeda; Speakers bureau: AbbVie, AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, Merck KGaA, MSD, Novartis, Pfizer, Roche, Takeda. S. Popat: Research funding to institution: Boehringer Ingelheim, Epizyme, BMS, Clovis Oncology, Roche, Lilly, Takeda; Honoraria: Boehringer Ingelheim, AstraZeneca, Roche, Takeda, Chugai Pharma; Consulting or advisory role: Boehringer Ingelheim, Roche, Novartis, Pfizer, AstraZeneca, BMS, MSD, Guardant Health, AbbVie; Travel, accommodations, expenses: Boehringer Ingelheim, BMS, Merck Sharp & Dohme. A. Morabito: Honoraria: AstraZeneca, Roche, Boehringer Ingelheim, Pfizer, MSD, BMS. S. Ghosh: Honoraria/speakers bureau: Pfizer. M. Tiseo: Speakers bureau, advisory role: AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, MSD, Novartis, Otsuka, Pfizer, Pierre Fabre, Roche. J. Haney, D. Kerstein: Employment, stock and other ownership interests: Arîad. D.R. Camidge: Honoraria: AstraZeneca, Takeda, Arrys/Kyn, Genoptix, G1 Therapeutics (DSMB), Mersana Therapeutics, Roche/Genentech, Ignyta, Daichii Sankyo (ILD adjudication committee), Hansoh SRC, Bio-Thera DSMB, Lycera, Revolution Med, Orion, Clovis, Celgene, Novartis); Research funding (ARIAD/Takeda). All other authors have declared no conflicts of interest.

    cffcb1a185b2d7d5c44e9dc785b6bb25

    Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

    Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.