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Clinical outcome of personalised treatment guided by genome and transcriptome sequencing in patients with neuroendocrine neoplasms: Updated results from the German NCT/DKTK MASTER trial

Date

08 Nov 2019

Session

Lunch and poster viewing

Presenters

Simon Kreutzfeldt

Citation

Annals of Oncology (2019) 30 (suppl_7): vii1-vii35. 10.1093/annonc/mdz238

Authors

S. Kreutzfeldt1, L. Apostolidis2, M. Oles1, P. Horak1, C.E. Heilig1, C. Heining3, B. Hutter4, B. Klink5, M. Lamping6, S. Uhrig4, A. Stenzinger7, E.C. Winkler2, B. Wiedenmann8, D. Jäger2, B. Brors4, E. Schröck5, U. Keilholz6, M.E. Pavel9, H. Glimm3, S. Fröhling1

Author affiliations

  • 1 Department Of Translational Medical Oncology, NCT Heidelberg, 69120 - Heidelberg/DE
  • 2 Department Of Medical Oncology, NCT Heidelberg, 69120 - Heidelberg/DE
  • 3 Translational Medical Oncology Department, National Center for Tumor Diseases, Partner site Dresden (NCT), 1309 - Dresden/DE
  • 4 Division Of Applied Bioinformatics, German Cancer Research Center, 69120 - Heidelberg/DE
  • 5 Instute Of Clinical Genetics, Faculty of Medicine Carl Gustav Carus, 01307 - Dresden/DE
  • 6 Charité Comprehensive Cancer Center, Charité - Universitätsmedizin Berlin, 10117 - Berlin/DE
  • 7 University Hospital Heidelberg, Institute of Pathology, 69120 - Heidelberg/DE
  • 8 Universitätsklinik Charité, Campus Virchow Klinikum, 13353 - Berlin/DE
  • 9 Gastroenterology And Hepatology, Endocrinology & Metabolic Diseases, Universitätsklinik Erlangen, 91054 - Erlangen/DE
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Resources

Background

Therapeutic options for neuroendocrine neoplasms (NEN) are limited, and only few NEN patients have been treated according to their individual genomic profile. We report the molecular and clinical characteristics of a large NEN cohort that was studied by prospective whole-genome (WGS), whole-exome (WES), and transcriptome sequencing (TS) within the NCT/DKTK MASTER precision oncology program.

Methods

Between 2013 and 2018, a total of 115 patients with advanced, heavily pretreated NEN were enrolled. Primary sites were gastrointestinal (n = 30), pancreatic/hepatic (n = 33), pulmonary (n = 20), genitourinary (n = 13), head/neck (n = 6), and other regions (n = 11). Grading according to the 2017 and 2019 WHO classification was neuroendocrine tumor (NET) G1, n = 12; NET G2, n = 31; NET G3, n = 12; neuroendocrine carcinoma, n = 36; mixed neuroendocrine-non-neuroendocrine neoplasm, n = 12; and other, n = 11.

Results

Of WES (n = 72) or WGS (n = 44) and TS (n = 92) were discussed in a multidisciplinary molecular tumor board. Recommendations were given in 103 cases (94%) for the following potential treatment alternatives: tyrosine or serine/threonine kinase inhibition (n = 67), PARP inhibition (n = 41), immunotherapy (n = 33), mTOR inhibition (n = 30), CDK4/6 inhibition (n = 19), MEK inhibition (n = 12), platinum-based chemotherapy (n = 7), BET inhibition (n = 7), anti-claudin18.2 (n = 5) or anti-DLL3 antibody treatment (n = 8). Somatic hypermutation (>10 mutations/megabase) was seen in 8.6% of patients. Treatment options could be implemented in 35 patients, of which 31 were evaluable for response: partial response, n = 10; mixed response, n = 1; stable disease, n = 11; progressive disease, n = 9; resulting in an overall response rate of 32% and a disease control rate of 71%.

Conclusions

Comprehensive genomic and transcriptomic characterization provides new insight into the molecular pathogenesis of NEN and creates therapeutic opportunities in a significant proportion of NEN patients who have exhausted standard treatment.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

NCT Heidelberg & German Cancer Consortium.

Funding

German Cancer Research Center.

Disclosure

S. Kreutzfeldt: Research grant / Funding (institution), Travel / Accommodation / Expenses: PharmaMar; Honoraria (self): Novartis; Research grant / Funding (institution): Roche; Travel / Accommodation / Expenses: Pfizer. C.E. Heilig: Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: PharmaMar; Honoraria (institution), Travel / Accommodation / Expenses: Lilly; Travel / Accommodation / Expenses: Novartis; Travel / Accommodation / Expenses: Celgene; Travel / Accommodation / Expenses: Teva; Travel / Accommodation / Expenses: BMS; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Pfizer. All other authors have declared no conflicts of interest.

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