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ePoster Display

533P - Efficacy and safety of entrectinib in patients with locally advanced/metastatic NTRK fusion-positive (NTRK-fp) solid tumours

Date

16 Sep 2021

Session

ePoster Display

Topics

Clinical Research;  Targeted Therapy

Tumour Site

Presenters

Lyudmila Bazhenova

Citation

Annals of Oncology (2021) 32 (suppl_5): S583-S620. 10.1016/annonc/annonc699

Authors

L. Bazhenova1, S.V. Liu2, J.J. Lin3, S. Lu4, A. Drilon5, S.P. Chawla6, M. Fakih7, M. Krzakowski8, L. Paz-Ares9, C. Blakely10, G.L. Buchschacher Jr11, P. Cassier12, Y. Fan13, G. Folprecht14, S. McCallum15, B. Pitcher16, D. Chen17, R. Freund18, C. Springfeld19

Author affiliations

  • 1 Department Of Medicine, Moores Cancer Center - University of California San Diego, 92093 - San Diego/US
  • 2 Lombardi Comprehensive Cancer Center, Georgetown University, Washington/US
  • 3 Department Of Hematology/oncology, Massachusetts General Hospital Cancer Center, Boston/US
  • 4 Shanghai Chest Hospital, Jiao Tong University, Shanghai/CN
  • 5 Department Of Medicine, Memorial Sloan Kettering Cancer Center, and Weill Cornell Medical College, New York/US
  • 6 N/a, Sarcoma Oncology Center, Santa Monica/US
  • 7 Department Of Medical Oncology & Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte/US
  • 8 Department Of Lung And Chest Cancer, Oncology Centre, Maria Skłodowska-Curie Institute, Warsaw/PL
  • 9 Medical Oncology Department, Hospital Universitario 12 de Octubre, CNIO-H12o Lung Cancer Clinical Research Unit, Universidad Complutense & Ciberonc, Madrid/ES
  • 10 Department Of Medicine, University of California San Francisco, San Francisco/US
  • 11 Department Of Hematology/oncology, Kaiser Permanente Southern California, Los Angeles Medical Center, Los Angeles/US
  • 12 Department Of Medicine, Centre Léon Bérard, Lyon/FR
  • 13 Medical Department Of Thoracic Oncology, Zhejiang Cancer Hospital, Hangzhou/CN
  • 14 Medical Department I Unit Medical Oncology, University Cancer Center, University Hospital Carl Gustav Carus, Dresden/DE
  • 15 Medication Safety And Risk Management, Genentech, Inc., South San Francisco/US
  • 16 Statistical Science, F. Hoffmann-La Roche Ltd, Mississauga/CA
  • 17 Clinical Science, Genentech, Inc., South San Francisco/US
  • 18 Medical Oncology, F. Hoffmann-La Roche Ltd, Basel/CH
  • 19 Department Of Medical Oncology, National Center for Tumor Diseases, Heidelberg University Hospital, Heidelberg/DE

Resources

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Abstract 533P

Background

NTRK gene fusions, resulting in chimeric TRK proteins, are oncogenic drivers in a diverse range of solid tumour types. Entrectinib is a potent, CNS-active TRK inhibitor approved for the treatment of adults with NTRK-fp solid tumours based on integrated analysis of three phase 1/2 trials: ALKA-372-001 (EudraCT 2012-000148-88); STARTRK-1 (NCT02097810); STARTRK-2 (NCT02568267). We present updated analyses with an additional 9 months of follow-up.

Methods

In this updated analysis (data cut-off 31 Aug 2020), tumours were assessed by blinded independent central review (BICR) per RECIST v1.1 (at end of cycle 1, then every 8 weeks). Primary endpoints were objective response rate (ORR) and duration of response (DoR); secondary endpoints included progression-free survival (PFS), overall survival (OS) and safety.

Results

The efficacy-evaluable cohort included 121 adults (vs 74 previously) with locally advanced/metastatic NTRK-fp solid tumours (enrolment cut-off 31 July 2019). Median age was 57 years, most patients (90.9%) had an ECOG PS 0–1 and 40.5% had received ≥2 prior lines of therapy. Median treatment duration was 11.0 months (range 0–49) and median survival follow-up was 25.8 months (95% CI 21.5–30.0). BICR ORR was 61.2% (n=74/121; 95% CI 51.9–69.9), including 19 (15.7%) complete responses. Responses were observed in all key tumour type categories (Table). Median BICR DoR was 20.0 months (95% CI 13.0–38.2). Median BICR PFS was 13.8 months (95% CI 10.1–19.9); median OS was 33.8 months (95% CI 23.4–46.4). In the safety-evaluable population (n=193), most treatment-related adverse events were grade 1/2 and non-serious, the most frequent being dysgeusia (35.2%), diarrhoea (31.1%), fatigue and weight increase (both 27.5%). Table: 533P

NTRK -fp tumour type category (n≥4) ORR, n/N (%) Median DoR, months (95% CI)
Sarcoma 15/26 (57.7) 15.0 (4.6–NE)
Salivary (MASC) 20/24 (83.3) NE (NE)
Non-small cell lung cancer 14/22 (63.6) 19.9 (10.4–29.4)
Thyroid 7/13 (53.8) 13.2 (7.9–NE)
Colorectal 2/10 (20.0) Range 15.2–20.0
Breast 5/7 (71.4) 12.9 (4.2–NE)
Neuroendocrine 2/5 (40.0) Range 11.1–32.9*
Pancreatic 3/4 (75.0) 12.9 (7.1–12.9)

Other tumour types included in efficacy-evaluable population: carcinoma of unknown primary (n=3); gynaecologic and head & neck cancers (n=2 each); neuroblastoma, gastrointestinal tract carcinoma, cholangiocarcinoma (n=1 each). *Censored. MASC, mammary analogue secretory carcinoma; NE, not estimable

Conclusions

In this updated analysis, in a larger cohort of patients with locally advanced/metastatic NTRK-fp solid tumours and longer follow-up, entrectinib continued to have clinically meaningful efficacy and was well tolerated.

Clinical trial identification

ALKA-372-001 (EudraCT 2012-000148-88); STARTRK-1 (NCT02097810); STARTRK-2 (NCT02568267).

Editorial acknowledgement

Medical writing support for the development of this abstract, under the direction of the authors, was provided by Laura Vergoz, PhD, of Ashfield MedComms, an Ashfield Health company, and funded by F. Hoffmann-La Roche Ltd.

Legal entity responsible for the study

F. Hoffmann-La Roche Ltd.

Funding

F. Hoffmann-La Roche Ltd.

Disclosure

L. Bazhenova: Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Advisory Role: Boehringer-Ingelheim; Financial Interests, Personal, Advisory Role: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Regeneron; Financial Interests, Institutional, Research Grant: BeyondSpring Pharma; Financial Interests, Personal, Stocks/Shares: Epic Sciences. S.V. Liu: Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Beigene; Financial Interests, Personal, Advisory Role: Blueprint; Financial Interests, Personal, Advisory Role: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Advisory Role: G1 Therapeutics; Financial Interests, Personal, Advisory Role: Genentech, Inc./F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Advisory Role: Guardant Health; Financial Interests, Personal, Advisory Role: Inivata; Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Advisory Role: Jazz Pharmaceuticals Lilly; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: PharmaMar; Financial Interests, Personal, Advisory Role: Regeneron; Financial Interests, Personal, Advisory Role: Takeda; Financial Interests, Institutional, Research Grant: Alkermes; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: Blueprint; Financial Interests, Institutional, Research Grant: Bristol-Myers Squibb; Financial Interests, Institutional, Research Grant: Corvus; Financial Interests, Institutional, Research Grant: Debiopharm; Financial Interests, Institutional, Research Grant: Elevation Oncology; Financial Interests, Institutional, Research Grant: Genentech, Inc.; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Merus; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Rain Therapeutics; Financial Interests, Institutional, Research Grant: RAPT; Financial Interests, Institutional, Research Grant: Turning Point Therapeutics. J.J. Lin: Financial Interests, Institutional, Principal Investigator: Hengrui Therapeutics; Financial Interests, Institutional, Principal Investigator: Turning Point Therapeutics; Financial Interests, Institutional, Principal Investigator: Neon Therapeutics; Financial Interests, Institutional, Principal Investigator: Relay Therapeutics; Financial Interests, Institutional, Principal Investigator: F. Hoffmann-La Roche Ltd/Genentech, Inc.; Financial Interests, Institutional, Principal Investigator: Pfizer; Financial Interests, Institutional, Principal Investigator: Bayer; Financial Interests, Institutional, Principal Investigator: Elevation Oncology; Financial Interests, Institutional, Principal Investigator: Novartis; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: C4 Therapeutics; Financial Interests, Personal, Advisory Role: Nuvalent; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim; Financial Interests, Personal, Advisory Role: Turning Point Therapeutics; Financial Interests, Personal, Advisory Role: Blueprint Medicines; Financial Interests, Personal, Advisory Role: Elevation Oncology; Financial Interests, Personal, Advisory Role: Genentech, Inc.; Financial Interests, Personal, Other, Honoraria: Chugai Pharmaceutical; Financial Interests, Personal, Other, CME funding: OncLive; Financial Interests, Personal, Other, CME funding: MedStar Health; Financial Interests, Personal, Other, CME funding: Northwell Health; Financial Interests, Personal, Other, Travel support: Pfizer. S. Lu: Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Hutchinson; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: Heng Rui; Financial Interests, Institutional, Research Grant: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim; Financial Interests, Personal, Advisory Role: Hutchinson MediPharma; Financial Interests, Personal, Advisory Role: Simcere; Financial Interests, Personal, Advisory Role: ZaiLab; Financial Interests, Personal, Advisory Role: GenomiCare; Financial Interests, Personal, Advisory Role: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Invited Speaker: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Invited Speaker: Hansoh; Financial Interests, Personal, Advisory Role: AstraZeneca. A. Drilon: Financial Interests, Personal, Speaker’s Bureau: Bayer; Financial Interests, Personal, Speaker’s Bureau: 14ner Oncology/Elevation Oncology; Financial Interests, Personal, Speaker’s Bureau: Meendi; Financial Interests, Personal, Speaker’s Bureau: Lilly; Financial Interests, Personal, Speaker’s Bureau: Merus; Financial Interests, Personal, Speaker’s Bureau: Nuvalent; Financial Interests, Personal, Speaker’s Bureau: Lancet Onology; Financial Interests, Personal, Speaker’s Bureau: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Speaker’s Bureau: Imedex; Financial Interests, Personal, Speaker’s Bureau: Novartis; Financial Interests, Personal, Royalties: Wolters Kluwer; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Exelixis; Financial Interests, Institutional, Research Grant: GlaxoSmithKline; Financial Interests, Institutional, Research Grant: Teva; Financial Interests, Institutional, Research Grant: Taiho; Financial Interests, Institutional, Research Grant: PharmaMar; Financial Interests, Personal, Research Grant: Foundation Medicine; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Prelude; Financial Interests, Personal, Advisory Role: 14ner Oncology/Elevation Oncology; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: Monopteros Therapeutics; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: GCC Global; Financial Interests, Personal, Advisory Role: Liberum; Financial Interests, Personal, Other, Expenses: Merck; Financial Interests, Personal, Other, Expenses: Puma; Financial Interests, Personal, Other, Expenses: Merus; Financial Interests, Personal, Other, Expenses: Beohringer Ingelheim; Financial Interests, Personal, Other, CME honoraria: Medscape; Financial Interests, Personal, Other, honoraria: OncLive; Financial Interests, Personal, Other, honoraria: PeerVoice; Financial Interests, Personal, Other, honoraria: Physicians Education Resources; Financial Interests, Personal, Other, honoraria: Targeted Oncology; Financial Interests, Personal, Other, honoraria: Research to Practice; Financial Interests, Personal, Other, honoraria: Axis; Financial Interests, Personal, Other, honoraria: Peerview Institute; Financial Interests, Personal, Other, honoraria: Paradigm Medical Communications; Financial Interests, Personal, Other, honoraria: WebMD; Financial Interests, Personal, Other, honoraria: MJH Life Sciences; Financial Interests, Personal, Other, Honoraria: Ignyta/Genentech, Inc./F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Other, Honoraria: Loxo/Bayer/Lilly; Financial Interests, Personal, Other, Honoraria: Takeda/Ariad/Millenium; Financial Interests, Personal, Other, Honoraria: TP Therapeutics; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Personal, Other, Honoraria: Blueprint Medicines; Financial Interests, Personal, Other, Honoraria: Helsinn; Financial Interests, Personal, Other, Honoraria: Beigene; Financial Interests, Personal, Other, Honoraria: BergenBio; Financial Interests, Personal, Other, Honoraria: Hengrui Therapeutics; Financial Interests, Personal, Other, Honoraria: Exelixis; Financial Interests, Personal, Other, Honoraria: Tyra Biosciences; Financial Interests, Personal, Other, Honoraria: Verastem; Financial Interests, Personal, Other, Honoraria: MORE Health; Financial Interests, Personal, Other, Honoraria: AbbVie; Financial Interests, Personal, Other, Honoraria: 14ner/Elevation Oncology; Financial Interests, Personal, Other, Honoraria: Remedica Ltd.; Financial Interests, Personal, Other, Honoraria: ArcherDX; Financial Interests, Personal, Other, Honoraria: Monopteros; Financial Interests, Personal, Other, Honoraria: Novartis; Financial Interests, Personal, Other, Honoraria: EMD Serono; Financial Interests, Personal, Other, Honoraria: Melendi; Financial Interests, Personal, Other, Honoraria: Liberum; Financial Interests, Personal, Other, Honoraria: Repare RX. S.P. Chawla: Financial Interests, Personal, Research Grant: Advenchen Laboratories; Financial Interests, Personal, Research Grant: Amgen; Financial Interests, Personal, Research Grant: Bayer; Financial Interests, Personal, Research Grant: Bristol-Myers-Squibb; Financial Interests, Personal, Research Grant: Elevar Therapeutics; Financial Interests, Personal, Research Grant: Five Prime Therapeutics; Financial Interests, Personal, Research Grant: GlaxoSmithKline; Financial Interests, Personal, Research Grant: Janssen Pharmaceutica; Financial Interests, Personal, Research Grant: Karyopharm Therapeutics; Financial Interests, Personal, Research Grant: NK Max America; Financial Interests, Personal, Research Grant: Philogen; Financial Interests, Personal, Research Grant: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Research Grant: SpringWorks Therapeutics; Financial Interests, Personal, Research Grant: Tyme Inc.; Financial Interests, Personal, Research Grant: US Biotest; Financial Interests, Personal, Stocks/Shares: AADi Bioscience; Financial Interests, Personal, Stocks/Shares: Cellestia; Financial Interests, Personal, Stocks/Shares: Immix Biopharma. M. Fakih: Financial Interests, Personal, Other, Honoraria: Amgen; Financial Interests, Personal, Advisory Role: Array; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Bayer Pharmaceuticals; Financial Interests, Personal, Speaker’s Bureau: Amgen; Financial Interests, Personal, Speaker’s Bureau: Guardant360; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Novartis. L. Paz-Ares: Financial Interests, Personal, Member of the Board of Directors: Genomica; Financial Interests, Personal, Member of the Board of Directors: Altum Sequencing; Financial Interests, Personal, Ownership Interest: Altum Sequencing; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: PharmaMar; Financial Interests, Personal, Advisory Role: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Merck Serono; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: PharmaMar; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: AbbVie; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Advisory Role: GlaxoSmithKline; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Ipsen; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim; Financial Interests, Personal, Advisory Role: Takeda; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Advisory Role: Tesaro; Financial Interests, Personal, Advisory Role: Blueprint Medicines; Financial Interests, Personal, Advisory Role: Mirati; Financial Interests, Personal, Leadership Role: European Medicines Agency; Financial Interests, Personal, Other, Travel, accommodation, expenses: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Other, Travel, accommodation, expenses: AstraZeneca; Financial Interests, Personal, Other, Travel, accommodation, expenses: Merck Sharp & Dohme; Financial Interests, Personal, Other, Travel, accommodation, expenses: BMS; Financial Interests, Personal, Other, Travel, accommodation, expenses: Pfizer; Financial Interests, Personal, Other, Travel, accommodation, expenses: Takeda. C. Blakely: Financial Interests, Personal, Other, Honoraria: Revolution Medicines; Financial Interests, Personal, Other, Honoraria: Amgen; Financial Interests, Personal, Other, Honoraria: Foundation Medicine; Financial Interests, Personal, Funding: Ignyta/F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Funding: Novartis; Financial Interests, Personal, Funding: AstraZeneca; Financial Interests, Personal, Funding: Mirati; Financial Interests, Personal, Funding: Spectrum; Financial Interests, Personal, Funding: MedImmune; Financial Interests, Personal, Funding: Takeda. G.L. Buchschacher Jr: Financial Interests, Institutional, Funding: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Other, Travel/accomodation expenses: F. Hoffmann-La Roche Ltd; Financial Interests, Institutional, Funding: Genentech, Inc.; Financial Interests, Personal, Other, Travel/accomodation expenses: Genentech, Inc.. P. Cassier: Financial Interests, Personal, Other, Honoraria: Novarits; Financial Interests, Personal, Other, Honoraria: F. Hoffmann-La Roche Ltd/Genentech, Inc.; Financial Interests, Personal, Other, Honoraria: Blueprint Medicines; Financial Interests, Personal, Other, Honoraria: Amgen; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Merck Serono; Financial Interests, Institutional, Other, Honoraria: Celgene; Financial Interests, Institutional, Other, Honoraria: Plexxikon; Financial Interests, Institutional, Other, Honoraria: AbbVie; Financial Interests, Institutional, Other, Honoraria: Bristol-Myers Squibb; Financial Interests, Institutional, Other, Honoraria: Merck Sharp & Dohme; Financial Interests, Institutional, Other, Honoraria: Taiho Pharmaceutical; Financial Interests, Institutional, Other, Honoraria: Toray Industries; Financial Interests, Institutional, Other, Honoraria: Transgene; Financial Interests, Institutional, Other, Honoraria: Loxo; Financial Interests, Institutional, Other, Honoraria: GlaxoSmithKline; Financial Interests, Institutional, Other, Honoraria: Innate Pharma; Financial Interests, Institutional, Other, Honoraria: Janssen; Financial Interests, Personal, Other, Travel, accommodation, expenses: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Other, Travel, accommodation, expenses: Amgen; Financial Interests, Personal, Other, Travel, accommodation, expenses: Novartis; Financial Interests, Personal, Other, Travel, accommodation, expenses: Bristol-Myers Squibb; Financial Interests, Personal, Other, Travel, accommodation, expenses: Merck Sharp & Dohme; Financial Interests, Personal, Other, Travel, accommodation, expenses: Netris Pharma. G. Folprecht: Financial Interests, Personal, Other, Honoraria: Bristol-Myers Squibb; Financial Interests, Personal, Other, Honoraria: Lilly/ImClone; Financial Interests, Personal, Other, Honoraria: Merck KGaA; Financial Interests, Personal, Other, Honoraria: Merck Sharp & Dohme; Financial Interests, Personal, Other, Honoraria: F. Hoffmann-La Roche Ltd/Genentech, Inc.; Financial Interests, Personal, Other, Honoraria: Sanofi/Aventis; Financial Interests, Personal, Other, Honoraria: Servier; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Role: Merck KGaA; Financial Interests, Personal, Advisory Role: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Role: Mundipharma; Financial Interests, Personal, Advisory Role: F. Hoffmann-La Roche Ltd/Genentech, Inc.; Financial Interests, Personal, Advisory Role: Sanofi/Aventis; Financial Interests, Personal, Advisory Role: Servier; Financial Interests, Personal, Funding: Merck KGaA. S. McCallum: Financial Interests, Personal, Full or part-time Employment: Genentech, Inc.. B. Pitcher: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd. D. Chen: Financial Interests, Personal, Full or part-time Employment: Genentech, Inc.. R. Freund: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd. C. Springfeld: Financial Interests, Personal, Advisory Role: Celgene; Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Advisory Role: Servier; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Other, Travel/accommodation expenses: Celgene; Financial Interests, Personal, Other, Travel/accommodation expenses: Servier. All other authors have declared no conflicts of interest.

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