PMID- 38420011
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240301
IS  - 2234-943X (Print)
IS  - 2234-943X (Electronic)
IS  - 2234-943X (Linking)
VI  - 14
DP  - 2024
TI  - Case report: First evidence of impressive efficacy of modulated dose 
      selpercatinib in a young Caucasian with ANK3-RET fusion-positive NSCLC.
PG  - 1307458
LID - 10.3389/fonc.2024.1307458 [doi]
LID - 1307458
AB  - Over the past decade, molecular characterization has led to change the management 
      of advanced non-small cell lung cancer (NSCLC) harboring driver mutations. 
      Rearranged during transfection (RET) gene fusions, occurring in 1% to 2% of 
      NSCLC, have emerged as an oncogenic druggable target. Systemic targeted therapies 
      with highly selective RET inhibitors (RETi), selpercatinib and pralsetinib, 
      represent a recent clinical breakthrough. While the development of RETi has 
      improved survival, with their increasing use, it is crucial to be aware of the 
      risks of rare but serious adverse events (AEs). A particular challenge for 
      clinicians in applying targeted therapies is not only diagnosing but also 
      interpreting rare mutations. Herein, we report a case of a 43-year-old Caucasian 
      advanced NSCLC patient diagnosed with a rare RET gene fusion, ANK3::RET, 
      identified with Next Generation Sequencing (NGS). Selpercatinib has been 
      initiated at the recommended initial dose after one incomplete chemotherapy cycle 
      due to a severe infusion reaction, but it subsequently required a dose adjustment 
      following grade 3 (G3) AEs. During treatment, we used a particular selpercatinib 
      dosage (160 mg in the morning and 80 mg in the evening) with good tolerance and 
      without compromising effectiveness. Our finding broadens the range of RET fusion 
      types in not-Asian NSCLC. To the best of our knowledge, our case demonstrates, 
      for the first time, a clinical and radiological response to frontline highly 
      selective RETi selpercatinib, expanding the spectrum of potential oncogenic RET 
      fusion partners in newly diagnosed NSCLC patients. Furthermore, to our knowledge, 
      this is the first case describing a RET fusion-positive (RET+) NSCLC patient 
      treated with a modified selpercatinib dosage outside the drug data sheet and 
      demonstrating a safe and effective use.
CI  - Copyright (c) 2024 De Carlo, Bertoli, Schiappacassi, Stanzione, Del Conte, Doliana, 
      Spina and Bearz.
FAU - De Carlo, Elisa
AU  - De Carlo E
AD  - Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), 
      Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Aviano, Italy.
FAU - Bertoli, Elisa
AU  - Bertoli E
AD  - Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), 
      Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Aviano, Italy.
AD  - Department of Medicine (DAME), University of Udine, Udine, Italy.
FAU - Schiappacassi, Monica
AU  - Schiappacassi M
AD  - Molecular Oncology Unit, Oncologia Molecolare e dei Modelli Preclinici di 
      Progressione Tumorale (OMMPPT) Department of Translational Research, Centro di 
      Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy.
FAU - Stanzione, Brigida
AU  - Stanzione B
AD  - Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), 
      Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Aviano, Italy.
FAU - Del Conte, Alessandro
AU  - Del Conte A
AD  - Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), 
      Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Aviano, Italy.
FAU - Doliana, Roberto
AU  - Doliana R
AD  - Molecular Oncology Unit, Oncologia Molecolare e dei Modelli Preclinici di 
      Progressione Tumorale (OMMPPT) Department of Translational Research, Centro di 
      Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy.
FAU - Spina, Michele
AU  - Spina M
AD  - Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), 
      Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Aviano, Italy.
FAU - Bearz, Alessandra
AU  - Bearz A
AD  - Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), 
      Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Aviano, Italy.
LA  - eng
PT  - Case Reports
DEP - 20240207
PL  - Switzerland
TA  - Front Oncol
JT  - Frontiers in oncology
JID - 101568867
PMC - PMC10900756
OTO - NOTNLM
OT  - NSCLC
OT  - RET fusion
OT  - RET inhibitors
OT  - next-generation sequencing
OT  - selpercatinib
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2024/02/29 06:43
MHDA- 2024/02/29 06:44
PMCR- 2024/01/01
CRDT- 2024/02/29 04:04
PHST- 2023/10/04 00:00 [received]
PHST- 2024/01/18 00:00 [accepted]
PHST- 2024/02/29 06:44 [medline]
PHST- 2024/02/29 06:43 [pubmed]
PHST- 2024/02/29 04:04 [entrez]
PHST- 2024/01/01 00:00 [pmc-release]
AID - 10.3389/fonc.2024.1307458 [doi]
PST - epublish
SO  - Front Oncol. 2024 Feb 7;14:1307458. doi: 10.3389/fonc.2024.1307458. eCollection 
      2024.