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R.M. Huber



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    Poster Display Session (ID 63)

    • Event: ELCC 2017
    • Type: Poster Display Session
    • Track:
    • Presentations: 2
    • Moderators:
    • Coordinates: 5/07/2017, 12:30 - 13:00, Hall 1
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      108P - NSCLC patients harbouring a rare or complex EGFR mutation are more often smokers and might not benefit from first line TKI therapy (ID 479)

      12:30 - 13:00  |  Author(s): R.M. Huber

      • Abstract

      Background:
      TKI therapy is definitely standard in first line treatment of patients with advanced NSCLC harbouring a classic EGFR mutation (Exon 19 deletion or Exon 21 L858R). However, a certain percentage of patients have rare or complex EGFR mutation with unknown relevance regarding prognosis and response to TKIs. For those patients, therapy decisions remain challenging.

      Methods:
      343 patients with NSCLC, who underwent EGFR mutation testing, were analysed in this study with regard to epidemiological characteristics as age, sex and smoking status as well to EGFR mutation status classified into wild type, classic, rare, synonymous, T790M and complex mutations. Further rare and complex mutations of 12 patients who received TKI therapy were analysed regarding to response to TKI treatment.

      Results:
      282 (82%) of all patients were EGRF wild type, whereas 61 (18%) harboured an EGFR mutation. Most of them appeared to be classic mutations 32 (9%), followed by rare (16 (5%)) and complex (7 (2%)) mutations. Synonymous and T790M resistance mutations were found in 3 and 4 patients respectively. EGFR mutations were significantly more frequent in women than in men. It was noticeable that patients with rare or complex mutations were significantly more often smokers compared to classic EGFR mutations. Further the rare and complex mutations showed to be less responsive to TKI therapy.

      Conclusions:
      Smoking seems to enhance the probability of rare or complex EGFR mutations. Besides, those mutations might not benefit from first line TKI therapy, so that the presence of EGFR mutation alone should not necessarily lead to induction of a TKI therapy and in case of TKI treatment to close surveillance. In fact, type of mutation, reports of response and patient characteristic as performance status should lead the decision.

      Clinical trial identification:


      Legal entity responsible for the study:
      Department of Internal Medicine V, University Munich

      Funding:
      Department of Internal Medicine V, University of Munich

      Disclosure:
      All authors have declared no conflicts of interest.

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      80TiP - A feasibility trial evaluating the addition of nivolumab to standard first-line chemo-radiotherapy in locally advanced stage IIIA/B NSCLC: The ETOP 6-14 NICOLAS trial (ID 455)

      12:30 - 13:00  |  Author(s): R.M. Huber

      • Abstract

      Background:
      Sequential or concomitant chemo-radiotherapy is the treatment of choice for stage III NSCLC. One attempt to improve the long-term survival is an immunotherapeutic strategy. The monoclonal antibody nivolumab targets and inhibits PD-1, an immune receptor on activated T-cells and responsible for abrogating anti-cancer immune response. The role of immune-checkpoint inhibitors is currently being evaluated in this indication as monotherapy or in combination with chemotherapy as well as after completion of chemo-radiotherapy but it has not yet been assessed in combination with radiotherapy. While anecdotal data of concurrent therapy suggests an acceptable toxicity profile, a formal prospective assessment is required before embarking on trials comparing concurrent versus sequential checkpoint inhibitors and radiotherapy.

      Trial design:
      NICOLAS is a phase II feasibility trial evaluating the administration of nivolumab concomitantly with standard first-line chemo-radiotherapy for locally advanced stage IIIA/B NSCLC. Additional inclusion criteria include adequate organ function and performance status 0-1. Chemotherapy consists of three cycles of cisplatin plus vinorelbine, etoposide or pemetrexed. Radiotherapy to the chest will be delivered either sequentially to or concurrently with chemotherapy. The initial nivolumab dose is 240 mg Q2W for eight cycles in the sequential, and 360 mg Q3W for four cycles in the concurrent chemo-radiotherapy schedule, followed by 480 mg Q4W for maximum one year for both regimens. A total of 43 patients will be recruited into the trial. The primary endpoint is grade > =3 pneumonitis observed up to 6 months after radiotherapy. The goal is to reject a 6-month pneumonitis-free rate of < =67%, tested at a rate of 85%, with 85% power and 5% one-sided alpha. An interim analysis will be performed after 21 patients have completed a 3-month follow-up on nivolumab treatment. Safety is closely monitored by the ETOP IDMC at their regular meetings every three months. NICOLAS is sponsored by ETOP with financial support of Bristol-Meyers Squibb. Accrual is ongoing and as of January 2017, 18 patients have been enrolled.

      Clinical trial identification:
      EudraCT: 2014-005097-11

      Legal entity responsible for the study:
      European Thoracic Oncology Platform (ETOP)

      Funding:
      Bristol-Meyers Squibb

      Disclosure:
      R.A. Stahel: Honoraria as consultant at advisory boards from Abbvie, Astra Zeneca, BMS, Boehringer Ingelheim, Eli Lilly, MSD, Pfizer and Roche and as speaker from Astellas, Astra Zeneca, Lilly, MSD, Novartis and Roche. R.M. Huber: Honoraria as consultant at advisory boards from BMS. All other authors have declared no conflicts of interest.

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    Targeted therapies and management of brain metastasis (ID 40)

    • Event: ELCC 2017
    • Type: Proffered Paper session
    • Track:
    • Presentations: 1
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      87O - Brigatinib in ALK+ NSCLC pts with intracranial CNS metastases in 2 clinical trials (ID 241)

      16:45 - 18:15  |  Author(s): R.M. Huber

      • Abstract
      • Presentation
      • Slides

      Background:
      The investigational next-generation anaplastic lymphoma kinase (ALK) inhibitor brigatinib is being evaluated in patients (pts) with ALK-positive non–small cell lung cancer (ALK+ NSCLC) in a phase 1/2 trial (Ph1/2) and a pivotal phase 2 trial (ALTA); most of these pts had intracranial central nervous system (CNS) metastases at baseline.

      Methods:
      In Ph1/2 (NCT01449461), pts with advanced malignancies, including ALK+ NSCLC, received brigatinib (30–300 mg/d). In ALTA (NCT02094573), crizotinib-resistant pts with advanced ALK+ NSCLC received brigatinib at 90 mg qd in arm A or 180 mg qd with a 7-day lead-in at 90 mg in arm B. ALK+ NSCLC pts with baseline brain metastases were analyzed. CNS efficacy in both trials and safety in ALTA are shown.

      Results:
      In Ph1/2 and ALTA, 50/79 (63%) and 154/222 (69%) ALK+ NSCLC pts had baseline brain metastases based on independent review committee (IRC) and investigator assessment, respectively. Most pts had received chemotherapy (Table). In Ph1/2, 25/50 (50%) pts were receiving brigatinib as of 16 November 2015; in ALTA, 101/154 (66%) pts were receiving brigatinib as of 29 February 2016. In pts with measurable brain lesions, confirmed intracranial objective response rate was 53% in Ph1/2 and 42%/67% in ALTA A/B (Table). In pts with only nonmeasurable brain lesions, 35% (11/31) in Ph1/2 and 7% (4/54)/18% (10/55) in ALTA A/B had confirmed complete resolution of brain lesions. Further data are shown in the table. The most common treatment-emergent adverse events (TEAEs) in the 151 treated ALTA pts with baseline brain metastases were nausea (A/B, 32%/43%), headache (30%/30%), diarrhea (18%/36%), cough (21%/30%), and vomiting (25%/26%); the most common grade ≥3 TEAEs were increased blood creatine phosphokinase (1%/11%), hypertension (4%/7%), increased lipase (3%/3%), and pneumonia (1%/4%).

      Conclusions:
      Brigatinib yielded substantial clinical activity in ALK+ NSCLC pts with brain metastases in 2 trials.rnTable: 87OBaseline characteristics and IRC-assessed intracranial efficacy of brigatinib in ALK+ NSCLC Pts with brain metastases at baselinern

      rnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrn
      rnPh1/2 n = 50ALTA Arm A n = 80ALTA Arm B n = 74
      Median age, years534955
      Received prior chemotherapy, %767476
      Crizotinib-naive, %800
      Pts evaluable for intracranial efficacy by IRC, n[a]468073
      Median iPFS, months14.615.612.8
      Pts with measurable brain lesions, n152618
      iORR, n (%)8 (53)11 (42)12 (67)
      iDCR, n (%)13 (87)22 (85)15 (83)
      No rad/active[b] subset, n91915
      iORR, n (%)6 (67)8 (42)11 (73)
      iDCR, n (%)8 (89)16 (84)14 (93)
      rniDCR = intracranial disease control rate, iORR = intracranial objective response rate (confirmed), iPFS = intracranial progression-free survivalrnaLast scan date: 8 October 2015 in Ph1/2; 14 April 2016 in ALTArnbNo prior brain radiotherapy in Ph1/2; active (untreated or treated and progressed) brain lesions in ALTArn

      Clinical trial identification:
      NCT01449461 and NCT02094573

      Legal entity responsible for the study:
      ARIAD Pharmaceuticals, Inc.

      Funding:
      ARIAD Pharmaceuticals, Inc.

      Disclosure:
      M. Tiseo: Consulting or advisory role (AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, Novartis, Otsuka, Pierre Fabre), research funding (ARIAD). R.M. Huber: Honoraria (ARIAD, AstraZeneca, BMS, Boehringer Ingelheim, Pfizer, Roche), consulting or advisory role (BMS, Boehringer Ingelheim, Celgene, Clovis Oncology, Eli Lilly, Novartis, Roche), research funding (Pierre Fabre). L.A. Bazhenova: Stock and other ownership interests (Epic Sciences), honoraria (Novartis), consulting or advisory role (AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Clovis Oncology, Genoptix, Heat Biologics, Pfizer, Roche/Genentech, Seattle Genetics, Trovagene), speakers bureau (AstraZeneca, Novartis, Pfizer, Roche/Genentech), research funding (AbbVie, ARIAD, Astellas, Astex, AstraZeneca/MedImmune, Boehringer Ingelheim, Chugai, Clovis Oncology, Eisai, Eli Lilly, Heat Biologics, Johnson & Johnson, Merck, Mirati, NanoCarrier, Novartis, Pfizer, Roche/Genentech). S-H.I. Ou: Advisory board (ARIAD). W. Reichmann, J. Haney, D. Kerstein: Employment, stock and other ownership interests (ARIAD). D.R. Camidge: Honoraria (ARIAD), research funding (ARIAD). S.N. Gettinger: Consulting or advisory role (ARIAD, BMS, Janssen), research funding (ARIAD, AstraZeneca/MedImmune, BMS, Boehringer Ingelheim, Incyte, Pfizer, Roche/Genentech). All other authors have declared no conflicts of interest.

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