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Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

1555 - Evolution and clinical impact of EGFR mutations in circulating free DNA in the BELIEF trial


20 Oct 2018


Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research


Alessandra Curioni


Annals of Oncology (2018) 29 (suppl_8): viii493-viii547. 10.1093/annonc/mdy292


A. Curioni1, E. Felip2, U. Dafni3, M. Molina4, O. Gautschi5, S. Peters6, B. Massutí7, R. Palmero8, S. Ponce9, E. Carcereny10, M. Früh11, M. Pless12, S. Popat13, S. Cuffe14, N. Karachaliou15, R. Kammler16, M. Kassapian17, H. Roschitzki-Voser16, R.A. Stahel1, R. Rosell15

Author affiliations

  • 1 Department Of Haematology And Oncology, Division Of Oncology, University Hospital Zurich, 8091 - Zurich/CH
  • 2 Institute Of Oncology, Vall d'Hebron University Hospital, 08035 - Barcelona/ES
  • 3 National And Kapodistrian University Of Athens And, Frontier Science Foundation-Hellas, 115 27 - Athens/GR
  • 4 Pangaea Biotech S.l., Quirón Dexeus University Hospital, Barcelona/ES
  • 5 Medical Oncology, Cantonal Hospital Lucerne, Lucern/CH
  • 6 Département D'oncologie, Centre Hospitalier Universitaire Vaudois - CHUV, 1011 - Lausanne/CH
  • 7 Isabial Oncologia Médica, Hospital Universitario Alicante, Alicante/ES
  • 8 Catalan Institute Of Oncology, Hospital Duran i Reynals, L’Hospitalet de Llobregat, Llobregat/ES
  • 9 Oncología Médica, Hospital Universitario 12 de Octubre, Madrid/ES
  • 10 Hospital Germans Trias I Pujol, Catalan Institute of Oncology, Badalona/ES
  • 11 Swiss Group For Clinical Cancer Research (sakk) And Department Of Oncology / Hematology, Cantonal Hospital St. Gallen, St. Gallen/CH
  • 12 Medical Oncology, Kantonsspital Winterthur, 8401 - Winterthur/CH
  • 13 Medical Oncology, Royal Marsden Hospital NHS Foundation Trust, London/GB
  • 14 Cancer Trials Ireland And Medical Oncology, St James's Hospital, 8 - Dublin/IE
  • 15 Institute Of Oncology Rosell, University Hospital Sagrat Cor, Barcelona/ES
  • 16 Coordinating Office, European Thoracic Oncology Platform (ETOP), 3008 - Bern/CH
  • 17 National And Kapodistrian University Of Athens, Frontier Science Foundation-Hellas, 115 27 - Athens/GR


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Abstract 1555


BELIEF, a single-arm, phase 2 trial, showed a median (med) progression-free survival (PFS) of 13.2 months (m) with erlotinib and bevacizumab in patients (pts) with advanced EGFR mutated NSCLC (Rosell et al 2017). We prospectively and longitudinally examined the evolution of sensitizing EGFR and p.T790M mutations, in circulating free DNA (cfDNA).


Blood samples were collected at baseline (BaS), at time of response (6w) and at progression (PD) and sent to a central laboratory. cfDNA was purified, and EGFR mutations were analyzed with real-time PCR assay. The fully validated assay is highly specific (>99%) and sensitive (76%) for EGFR sensitizing mutations.


As of 12 March 2018, at a med follow-up of 47m (IQR: 42, 59), 2 pts (2%) are still on full protocol treatment, while 95 PFS events (87%) and 70 deaths (64%) have occurred. The med PFS is 13.2m (95% CI: 10.3, 15.5), the med overall survival (OS) is 30.2m (95% CI: 23.1, 39.6) and the 2-year OS is 58.4% (95% CI: 48.2-67.2%). cfDNA are available at BaS for 91 pts, at 6w for 72 pts and at PD for 58 pts. EGFR mutations identified in blood were also originally found in tissue. 69 pts had cfDNA assessment both at BaS and 6w. Med PFS was 19.1m for 24 pts without EGFR mutations in cfDNA at BaS and at 6w, versus 12.6m for 43 pts with EGFR mutations detected in cfDNA at BaS, but not at 6w (p = 0.019). 46 pts had the 3-pronged assessments (BaS, 6w, PD). The med PFS for the BaS negative group that remained negative at PD was 17.4m (12 pts), while for the BaS positive group that converted to negative at 6w and remained negative at PD was 13.1m (7pts; p = 0.72). For those BaS positive who converted to negative at 6w, but later became positive again at PD, the med PFS was 10.6m (p = 0.20). At PD, 41% of pts harbored T790M. For pts with BaS EGFR mutations, the med PFS was 13.4m (16 pts) in those without T790M, and 9m (17 pts) for the T790M mutated at PD (p = 0.14).


These data suggest the absence of sensitizing EGFR mutations in cfDNA at BaS confers significantly better PFS than in pts with EGFR mutant cfDNA. A trend of shorter PFS is seen in the subgroup of pts with BaS EGFR mutant cfDNA, from whom, at PD, EGFR mutations were again detected. EGFR mutant cfDNA could be an indicator for co-occurring oncogenic events and the use of cfDNA exome platforms should be encouraged.

Clinical trial identification


Legal entity responsible for the study

European Thoracic Oncology Platform (ETOP)


Hoffmann-La Roche.

Editorial Acknowledgement


A. Curioni: Research support: Novartis; Honoraria: MSD, BMS, Boehringer Ingelheim, Roche, Pfizer, Novartis, AstraZeneca. E. Felip: Advisory board and speaker's bureau: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celegene, Eli Lilly, Guardant Health, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Takeda, Abbvie, Merck. B. Massutí: Consulting or advisory role: Roche, Boehringer Ingelheim, BMS, MSD, AstraZeneca; Speaker's bureau: Roche, Amgen, Merck Serono, Pfizer, AstraZeneca, Boehringer Ingelheim; Travel grants: MSD, Janssen, Roche. M. Früh: Research support: BMS, AstraZeneca; Honoraria to institution for advisory: MSD, Roche, AstraZeneca, BMS, Boehringer Ingelheim. M. Pless: Advisory board role: Roche. S. Popat: Honoraria: Boehringer Ingelheim, AstraZeneca, Roche, Takeda, Chugai Pharma; Consulting or advisory role: Boehringer Ingelheim, Roche, Novartis, Pfizer, AstraZeneca, BMS, MSD, Guardant Health, Abbvie; Travel grants: Boehring Ingelheim, BMS, MSD; Research funding to institution: Boehringer Ingelheim, Epizyme, BMS, Clovis Oncology, Roche, Lilly, Takeda. S. Cuffe: Sponsorship of travel, registration, accommodation for attendances at conferences: ASCO, WCLC from Pfizer, BMS, MSD, Amgen, Roche, Ipsen. R.A. Stahel: Consulting or advisory role: Roche; Speaker's bureach: Roche. All other authors have declared no conflicts of interest.

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