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M.T. Moran Bueno



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    Poster Display session (Friday) (ID 65)

    • Event: ELCC 2018
    • Type: Poster Display session
    • Track:
    • Presentations: 3
    • Moderators:
    • Coordinates: 4/13/2018, 12:30 - 13:00, Hall 1
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      156P - ASTRIS, a real-world study with osimertinib in patients with non-small cell lung cancer (NSCLC) EGFR T790M mutated: Characteristics and diagnostic methods used for patients included in Spain (ID 547)

      12:30 - 13:00  |  Author(s): M.T. Moran Bueno

      • Abstract

      Background:
      We present demographic and diagnostic data for the first planned interim analysis of ASTRIS study, currently ongoing.

      Methods:
      ASTRIS is a single-arm, open-label, phase IIIb clinical trial to evaluate the efficacy and safety of osimertinib monotherapy in real practice. Eligible patients had stage IIIB-IV NSCLC with a T790M mutation determined by a locally validated test (not restricted by sample type), had received at least a previous EGFR-TKI, ECOG 0-2, with no history of interstitial lung disease or QTc prolongation. Asymptomatic and stable CNS metastases were allowed. Patients received osimertinib 80 mg once daily.

      Results:
      We included 132 patients in 18 centers, 130 began treatment. At data cut-off (3 Nov 2016), 72% continued in the study, median follow-up 5.2 (<1–12) months. Median age 66 (32–89) years, 69% women, 98% caucasian, 85% ECOG 0/1, 15% ECOG 2, 84% stage IV, 40% cerebral / leptomeningeal metastasis, 42% previous chemotherapy, 34% previous radiotherapy. EGFR-TKIs: gefinitib (43%), erlotinib (57%), afatinib (17%) and dacomitinib (2%). Only patients with a T790M positive test result were treated in the study: 73 (56%) were recruited to the study after a positive tissue test, 47 (36%) after a positive plasma test, 4 (3%) cytology and 6 (5%) after testing another specimen type. The origin of the biopsy tissue was primary tumor (60%), metastasis (40%). The local laboratory was used in 62% of the patients. Testing methods: Roche cobas (50%), Qiagen therascreen (17%), PCR-Invader (20%), TaqMan (9%), ARMS-PCR (1%), Illumina MiSeq / HiSeq (1%), AMOY (1%) and others (2%). Other EGFR mutations were EXON 19 deletions (58%), L858R (27%), S768I (5%) and G719X (3%).

      Conclusions:
      The patient profile included in the study expands the patient population studied in the published studies, including excluded patients (PS-2, treated with non-marketed TKIs) or characteristics typical of the Spanish population, with a majority of Caucasians. The data from the ASTRIS study will give external validity to the results obtained in studies published with osimertinib.

      Clinical trial identification:
      NCT02474355

      Legal entity responsible for the study:
      AstraZeneca

      Funding:
      AstraZeneca

      Disclosure:
      D. Vicente Baz: Consultant or Advisory Role: Astra Zeneca, BMS, Pfizer, Roche Research Funding: Pfizer, Boehringer. G. Marquez: AstraZeneca employee. All other authors have declared no conflicts of interest.

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      159P - Clinical activity of afatinib in a cohort of patients with lung adenocarcinoma harbouring uncommon EGFR mutations: A Spanish retrospective multicentre study (ID 269)

      12:30 - 13:00  |  Presenting Author(s): M.T. Moran Bueno

      • Abstract

      Background:
      Uncommon EGFR mutations (u-EGFRm) in exons 18–21 account for 12–15% of overall EGFR mutations in non-small cell lung cancer (NSCLC). Afatinib has shown activity against some u-EGFRm, especially G719X, L861Q, and S768I; although other u-EGFRm (Ins20, de novo T790M) have a lower likelihood of response. U-EGFRm are a heterogeneous group of molecular alterations and have also been reported as co-mutations with other EGFR mutations (complex mutations). We examined the molecular and clinical characteristics and efficacy of afatinib in a cohort of patients with advanced NSCLC patients carrying u-EGFRm in Spanish clinical practice.

      Methods:
      Medical records of 67 NSCLC patients with u-EGFRm treated with afatinib between 2012 and 2017 at 23 Spanish institutions were reviewed. U-EGFRm were analysed as complex mutations (Group A), Ins20 (Group B), or single mutations (Group C). Efficacy data were evaluated in terms of tumour response and overall survival (OS).

      Results:
      Of the 67 patients, 96% were Caucasian, all were adenocarcinoma, 46% were never smokers and 37% were former smokers, 79% were Stage IV at diagnosis, 79% had ECOG PS 0–1. Group A complex u-EGFRm consisted of double mutations of G719X + E709F, G719X + S768I, G719X + L861Q, L858R + T790M, L858R + S768I, Del19 + S768I, Del19 + L747S, or R776C + L861Q. No differences in clinical characteristics were found between Group A (n = 20), Group B (n = 23), and Group C (n = 24). Afatinib was administered as 1st line therapy in 80% of patients. Median time on therapy was 4.2 months (range 2.0–12.9). Eighteen percent of patients started afatinib at a reduced dose and 24% of patients required a dose reduction. Response to afatinib was significantly higher in Group A and C (70% and 54%, respectively), compared with Group B (13%; pairwise comparison p < 0.001 and 0.013, respectively, Table). Median OS (mOS) for the entire cohort was 19.9 months (9.7–30.1). Hazard ratio for OS were 0.27 (95% CI 0.10-0-71; p = 0.009) and 0.40 (95% CI 0.17–0.95; p = 0.037) for Group A and C compared to Group B, respectively.

      u-EGFRmGroup A (complex)n = 20Group B (Ins20)n = 23Group C (other)n = 24
      Response to afatinib, n (%)
      Complete response1 (5.0)0 (0)1 (4.2)
      Partial response13 (65.0)3 (13.0)12 (50.0)
      Stable disease3 (15.0)8 (34.8)5 (20.8)
      Progressive disease0 (0)10 (43.5)3 (12.5)
      Not evaluable3 (15.0)2 (8.7)3 (12.5)
      mOS (95% CI), months28.8 (20.7–36.8)10.7 (6.2–15.3)19.9 (10.8–29.0)
      p = 0.014


      Conclusions:
      In clinical practice, afatinib was active in u-EGFRm NSCLC, particularly in complex and single mutations. Further strategies are needed for patients with ins20, a subgroup u-EGFRm with a lower clinical benefit from afatinib.

      Clinical trial identification:


      Legal entity responsible for the study:
      Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain

      Funding:
      Has not received any funding

      Disclosure:
      All authors have declared no conflicts of interest.

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      66P - PALB2 mRNA expression as a predictive marker in advanced non-small cell lung cancer (NSCLC) patients (p) treated with docetaxel-cisplatin (ID 405)

      12:30 - 13:00  |  Author(s): M.T. Moran Bueno

      • Abstract
      • Slides

      Background:
      PALB2, the partner and localizer of BRCA2, binds directly to BRCA1 and is essential for homologous recombination repair and, henceforth, could influence the effect of docetaxel-cisplatin therapy. Previous studies have shown that PALB2 impedes the degradation of nuclear factor erythroid 2-related factor 2 (NRF2) through the binding and sequestration of its inhibitor Kelch-like ECH-associated protein (KEAP1). Over-expression of NRF2 could activate NOTCH signaling and lead to enrichment of cancer stem cells. In the current study, we examine the mRNA levels of PALB2 in advanced NSCLC p treated with docetaxel-cisplatin.

      Methods:
      We assessed PALB2 mRNA levels as potential biomarkers in tumor tissue from 177 cisplatin plus docetaxel-treated NSCLC p from the NCT00617656/GECP-BREC trial. The relationship of the PALB2 mRNA levels with the PFS, OS and response were examined.

      Results:
      Median age 62; 79.1% male; 51.4% adenocarcinoma. Results of PALB2 mRNA expression were as follows: PFS was 5.6 months (m) for p with high/intermediate (H-I) PALB2 and 4.1 m for p with low (L) PALB2 (p = 0.0018). OS was 13.2 m for p with H-I PALB2 compared to 9.9 for p with L PALB2 (p = 0.0377). In the univariate analysis, H-I PALB2 was a marker of longer PFS (HR = 0.56, 95% CI, 0.38, 0.80; p = 0.002) and OS (HR = 0.64, 95% CI, 0.41, 0.98; p = 0.0394). In the multivariate analysis, only H-I PALB2 was associated with longer PFS (here HR = 0.56 and p = 0.0022) and OS (HR = 0.61 and p = 0.0343). Among 143 p with data for response and PALB2 expression, 49.5% of p with H-I PALB2 were responders, compared to only 28% with L PALB2 (p = 0.0131).

      Conclusions:
      Higher PALB2 mRNA levels were associated with higher response, longer PFS and OS in NSCLC p treated with docetaxel-cisplatin. However, PALB2 could also be a readout of NRF2 activity and NOTCH signaling, indicative of an increase in cancer stem cells, providing hints for combinatory therapy with gamma secretase inhibitors to prevent the increase of stem-like cells and further improve outcome to docetaxel-cisplatin therapy. Experiments in NSCLC cell lines are ongoing.

      Clinical trial identification:


      Legal entity responsible for the study:
      IGTP, Germans Trias i Pujol Research Institute, Badalona, Barcelona, Spain

      Funding:
      Fundació Obra Social “La Caixa”

      Disclosure:
      All authors have declared no conflicts of interest.

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