PMID- 35647935
OWN - NLM
STAT- MEDLINE
DCOM- 20220822
LR  - 20221012
IS  - 1945-7197 (Electronic)
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 107
IP  - 9
DP  - 2022 Aug 18
TI  - Selpercatinib Treatment of RET-Mutated Thyroid Cancers Is Associated With 
      Gastrointestinal Adverse Effects.
PG  - e3824-e3829
LID - 10.1210/clinem/dgac337 [doi]
AB  - CONTEXT: Metastatic medullary thyroid carcinoma (MTC) and radioactive 
      iodine-refractory differentiated thyroid carcinoma (RAI-R DTC) have poor 
      prognosis and limited treatment options. Selpercatinib (LOXO-292), a selective 
      kinase inhibitor targeting the RET gene, has shown a 69% to 79% objective 
      response rate in this cohort with benefits in other tumors including lung cancer 
      harboring the same oncogenic driver. Published reports describe only 17% of 
      patients experiencing gastrointestinal (GI) adverse effects (AEs), which is in 
      contrast to our local experience. OBJECTIVE: Here we characterize the AEs and 
      correlate them with radiological and histopathological findings. METHODS: 
      Sequential patients enrolled in LIBRETTO-001 at Royal North Shore Hospital, 
      Sydney, Australia, with available imaging (n = 22) were recruited. Patients had 
      regular visits with AEs documented and computed tomography (CT) scans every 3 
      months. CT at screening, at time of GI AE, and at most recent follow-up were 
      reviewed and scored. Endoscopic examination was performed in 5 patients. RESULTS: 
      Of 22 patients in this cohort, the majority had somatic RET alterations (n = 18), 
      most commonly p.Met918Thr (n = 14). Ten patients (50%) developed GI AEs. Dose 
      reduction was required in 8 of the 10 patients, but none discontinued therapy. 
      The majority had stable disease (n = 17). Gastric and small-bowel edema was 
      evident in symptomatic patients after a median time of 67 weeks' treatment. 
      Histological correlation in 5 patients revealed mucosal edema correlating with 
      radiological evidence of congestion and edema. CONCLUSION: GI AEs with 
      selpercatinib may be more common than previously described. Most are 
      self-limiting but often require dose adjustments. Histological evidence of 
      mucosal edema observed in conjunction with the radiological findings of 
      congestion and wall thickening suggest bowel-wall edema is a predominant 
      mechanism of abdominal pain in these patients.
CI  - (c) The Author(s) 2022. Published by Oxford University Press on behalf of the 
      Endocrine Society.
FAU - Tsang, Venessa
AU  - Tsang V
AUID- ORCID: 0000-0001-7583-9175
AD  - Department of Endocrinology, Royal North Shore Hospital, NSW 2065, Sydney, 
      Australia.
AD  - Northern Clinical School, Faculty of Medicine and Health, University of Sydney, 
      NSW 2006, Australia.
FAU - Gill, Anthony
AU  - Gill A
AD  - Northern Clinical School, Faculty of Medicine and Health, University of Sydney, 
      NSW 2006, Australia.
AD  - NSW Health Pathology Department of Anatomical Pathology, Royal North Shore 
      Hospital, NSW 2065, Sydney, Australia.
FAU - Gild, Matti
AU  - Gild M
AD  - Department of Endocrinology, Royal North Shore Hospital, NSW 2065, Sydney, 
      Australia.
AD  - Northern Clinical School, Faculty of Medicine and Health, University of Sydney, 
      NSW 2006, Australia.
FAU - Lurie, Brett
AU  - Lurie B
AD  - Department of Radiology, Royal North Shore Hospital, NSW 2065, Sydney, Australia.
FAU - Blumer, Lucy
AU  - Blumer L
AD  - Department of Radiology, Royal North Shore Hospital, NSW 2065, Sydney, Australia.
FAU - Siddall, Rhonda
AU  - Siddall R
AD  - Department of Endocrinology, Royal North Shore Hospital, NSW 2065, Sydney, 
      Australia.
FAU - Clifton-Bligh, Roderick
AU  - Clifton-Bligh R
AD  - Department of Endocrinology, Royal North Shore Hospital, NSW 2065, Sydney, 
      Australia.
AD  - Northern Clinical School, Faculty of Medicine and Health, University of Sydney, 
      NSW 2006, Australia.
FAU - Robinson, Bruce
AU  - Robinson B
AD  - Department of Endocrinology, Royal North Shore Hospital, NSW 2065, Sydney, 
      Australia.
AD  - Northern Clinical School, Faculty of Medicine and Health, University of Sydney, 
      NSW 2006, Australia.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Iodine Radioisotopes)
RN  - 0 (Pyrazoles)
RN  - 0 (Pyridines)
RN  - CEGM9YBNGD (selpercatinib)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-ret)
RN  - EC 2.7.10.1 (RET protein, human)
SB  - IM
MH  - Gastrointestinal Tract/drug effects
MH  - Humans
MH  - Iodine Radioisotopes/therapeutic use
MH  - Proto-Oncogene Proteins c-ret/genetics
MH  - Pyrazoles/adverse effects/therapeutic use
MH  - Pyridines/adverse effects/therapeutic use
MH  - *Thyroid Neoplasms/drug therapy/genetics/pathology
PMC - PMC9387698
OTO - NOTNLM
OT  - RET mutation
OT  - adverse effects
OT  - bowel oedema
OT  - histology
OT  - radiology
OT  - selpercatinib
OT  - thyroid carcinoma
EDAT- 2022/06/02 06:00
MHDA- 2022/08/23 06:00
PMCR- 2022/06/01
CRDT- 2022/06/01 12:06
PHST- 2022/02/16 00:00 [received]
PHST- 2022/06/02 06:00 [pubmed]
PHST- 2022/08/23 06:00 [medline]
PHST- 2022/06/01 12:06 [entrez]
PHST- 2022/06/01 00:00 [pmc-release]
AID - 6596759 [pii]
AID - dgac337 [pii]
AID - 10.1210/clinem/dgac337 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2022 Aug 18;107(9):e3824-e3829. doi: 
      10.1210/clinem/dgac337.