Abstract 572P
Background
Endocrine neoplasms encompass a heterogeneous group of tumors, some of which lack optimal therapeutic options. The emergence of new targeted agents directed against specific genetic alterations may change their clinical outcome. We evaluated the prevalence of genetic alterations among advanced endocrine tumors and outcomes of patients treated with targeted agents.
Methods
Retrospective study of patients with advanced endocrine tumors evaluated with a DNA-based next generation sequencing (NGS) platform for a molecular and personalized therapeutic approach during 2020.
Results
The analysis of 27 endocrine tumors identified 76 pathogenic alterations and 175 variants of uncertain significance. Most mutations occurred in genes involved in tyrosine kinase pathways (50%), chromatin remodeling (17%), DNA damage repair (12%) and transcription regulation (12%). In 5 patients (pts) with neuroendocrine carcinomas, mutations in PIK3CA (N=2) and TP53 (N=2) were found. Among 7 pts with papillary thyroid cancer, 5 had a BRAFV600E mutation (3 with concomitant TERT promoter mutations) and 2 other tumors had alterations in NRAS (N=1) (with concomitant TERT promoter mutation) and RET genes (N=1). Three out of 4 follicular thyroid cancers harbored a potentially targetable mutation, such as PIK3CA, KRAS and PTEN. A RET mutation was identified in 5 out of 6 medullary thyroid cancers (M918T in 4/5 and C630R in 1/5) and a co-mutation in NTRK1 was also found in 1 patient. All 3 patients with anaplastic thyroid cancer (ATC) harbored a TERT promoter mutation. Two of them had a BRAFV600E mutation. Seven out of 27 pts (26%) received targeted therapy. Two pts with BRAF mutated ATC received treatment with dabrafenib + trametinib, reaching an ORR of 100% and median PFS of 10 months. Five pts with RET mutated medullary thyroid cancer were treated with a selective RET inhibitor, achieving an ORR of 80%. All responders continued on treatment at the time of this analysis.
Conclusions
70% of pts harbored an actionable mutation. Targeted therapy resulted in outstanding response rates and may have a significant survival benefit in aggressive tumors, such as ATC. Genetic alterations in targetable genes should be routinely evaluated in advanced endocrine tumors.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
J. Molina-Cerrillo: Financial Interests, Personal, Invited Speaker: IPSEN; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Personal, Invited Speaker: EISAI; Financial Interests, Personal, Research Grant: Pfizer; Financial Interests, Personal, Research Grant: IPSEN. P. Valderrábano: Financial Interests, Personal, Writing Engagements: Sanofi-Genzyme; Financial Interests, Personal, Invited Speaker: Esteve. A. Carrato Mena: Non-Financial Interests, Institutional, Advisory Role: Roche; Non-Financial Interests, Institutional, Advisory Role: Bayer; Non-Financial Interests, Institutional, Advisory Role: Merk; Non-Financial Interests, Institutional, Advisory Role: MSD; Non-Financial Interests, Institutional, Advisory Role: BMS; Non-Financial Interests, Institutional, Advisory Role: Servier; Non-Financial Interests, Institutional, Advisory Role: Celgene; Non-Financial Interests, Institutional, Advisory Role: Shire; Non-Financial Interests, Institutional, Advisory Role: Mylan. P. Garrido Lopez: Financial Interests, Personal, Advisory Board: Abbvie; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Gebro; Financial Interests, Personal, Advisory Board: GlaxoSmithKline; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Advisory Board: Nordic; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Takeda; Financial Interests, Personal, Principal Investigator: Apollomics; Financial Interests, Personal, Principal Investigator: Array Biopharma; Financial Interests, Personal, Principal Investigator: BluePrint; Financial Interests, Personal, Principal Investigator: IO Biotech; Non-Financial Interests, Personal, Leadership Role: AECC; Non-Financial Interests, Personal, Leadership Role: ESMO; Non-Financial Interests, Personal, Leadership Role: FACME; Non-Financial Interests, Personal, Leadership Role: IASLC; Non-Financial Interests, Personal, Leadership Role: SEOM. T. Alonso-Gordoa: Financial Interests, Personal, Invited Speaker: IPSEN; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: Astellas; Financial Interests, Personal, Advisory Role: Janssen-Cilag; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: EISAI; Financial Interests, Personal, Invited Speaker: Merck. All other authors have declared no conflicts of interest.