Abstract 4572
Background
Therapeutic options for neuroendocrine neoplasms (NEN) are limited. Within the NCT/DKTK-MASTER precision oncology trial, we apply prospective whole-genome (WGS), whole-exome (WES), and transcriptome sequencing (TS) in a wide range of solid tumors to evaluate the feasibility of optimizing treatment by deep analysis of genomic alterations. Here we report the first clinical results of the NEN cohort within this study.
Methods
Between 2012 and 2017, we included 84 NEN patients. All patients had advanced disease and had received at least one line of prior standard therapy. We performed WES (n = 60) or WGS (n = 24) and TS (n = 69). Molecular findings (somatic/germline small nucleotide variants, insertions, deletions, copy number variations, mutational burden and signatures, homologous recombination deficiency scores, gene expression patterns, etc.) were discussed in a molecular tumor board, and recommendations were sent to the treating physician.
Results
Based on WES/WGS/TS, we recommended genomics-guided treatment in 74 patients (88%). Treatment recommendations were grouped as follows: PARP inhibition (n = 31), immunotherapy (n = 22), mTOR inhibition (n = 22), multi-kinase inhibition (n = 13), CDK4/6 inhibition (n = 12), tyrosine or serine/threonine kinase inhibition (ALK, n = 1; ERBB, n = 5; FGFR, n = 5; MET, n = 2; RET, n = 7; VEGFR, n = 3), MEK inhibition (n = 6), chemotherapy (n = 3) or other (n = 34). 17 patients received recommended therapies. Among those, 11 were evaluable for response with 4 partial responses (PR), 2 stable (SD) and 5 progressive diseases (PD). 25 patients died before therapy could be started, 9 patients are currently receiving other successful regimens, for 12 patients follow-up data are still pending.Table: 1310PD
| Histology | Primary sites | Genomics-guided treatments | |||||||
|---|---|---|---|---|---|---|---|---|---|
| HN | Th | GI | Lv/Pc | UG | oth | success (PR or SD) | not evaluable | no success (PD) | |
| NET G1 | 1 | 2 | 3 | MKI1 | |||||
| NET G2 | 1 | 5 | 5 | 14 | 1 | 1 | Cx2, METInh3, PARPInh4, CI5 | MKI10 | |
| NET G3 | 1 | 4 | PARPInh4, CI5, MKI7 | ALKInh11 | |||||
| NEC G3 | 2 | 5 | 12 | 6 | 5 | 4 | mTORInh6 | FGFRInh8, METInh9 | 2x PARPInh4 |
| MANEC | 1 | 7 | 1 | 3 | CI5 | CI5 |
HN = head & neck, Th = thorax, GI = gastrointestinal, Lv/Pc = liver & pancreas, UG = urogenital, oth = other
1sunitinib, 2EWSR-FLI-fusion lead to ewing-sarcoma chemotherapy treatment, 3cabozantinib, 4olaparib, 5checkpoint-inhibitor, 6everolimus, 7pazopanib, 8ponatinib, 9crizotinib, 10vandetanib, 11alectinib
Conclusions
Extensive genomic and transcriptomic characterization offers valuable insight into pathogenic mechanisms in NEN and facilitates optimized treatment for certain patients. Genomic landscape data and predictive biomarker analysis are currently in preparation.
Clinical trial identification
This trial has been approved by the institutional research ethics committee (approval S-206/2011).
Legal entity responsible for the study
National Center for Tumor Diseases (NCT) Heidelberg.
Funding
Grant H021 from DKFZ-HIPO (Heidelberg Center for Personalized Oncology), Joint Funding Project grant from DKTK (German Cancer Consortium).
Editorial Acknowledgement
Disclosure
All authors have declared no conflicts of interest.