High-dose alectinib for RET fusion-positive non-small cell lung cancer in the Blood First Assay Screening Trial

Rafal Dziadziuszko; Nir Peled; Tony Mok; Solange Peters; Santiago Ponce Aix; Jorge Alatorre-Alexander; Brian D. Vicuna; Margaret Maclennan; Vijay Bhagawati-Prasad; Sarah M. Shagan; Erica Schleifman; Thorsten Ruf; Michael S. Mathisen; Shirish M. Gadgeel

doi:10.5114/wo.2023.135246

High-dose alectinib for RET fusion-positive non-small cell lung cancer in the Blood First Assay Screening Trial

Rafal Dziadziuszko, Nir Peled, Tony Mok, Solange Peters, Santiago Ponce Aix, Jorge Alatorre-Alexander, Brian D. Vicuna, Margaret Maclennan, Vijay Bhagawati-Prasad, Sarah M. Shagan, Erica Schleifman, Thorsten Ruf, Michael S. Mathisen, Shirish M. Gadgeel

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

Introduction: This paper presents results from Cohort B (rearranged during transfection [RET], fusion-positive) of the Blood First Assay Screening Trial in patients with advanced non-small cell lung cancer (NSCLC) screened for genetic alterations using blood-based next-generation sequencing. Material and methods: Adults with advanced RET fusion-positive NSCLC received alectinib 900 mg twice daily (BID) in Phase I. Enrolment closed prematurely with Phase II uninitiated. Results: Among eight treated patients, confirmed best overall responses in evaluable patients were stable disease (4/5) and progressive disease (1/5). One dose-limiting toxicity (death, unknown cause) was considered by the investigator to be related to treatment and underlying disease. Serious adverse events (SAEs) occurred in five patients, and SAEs that may be related to treatment occurred in two patients. Conclusions: Alectinib showed limited activity in advanced RET fusion-positive NSCLC, and further investigation was not conducted due to the development of selective RET inhibitors pralsetinib and selpercatinib. No new safety signals were observed, and the safety profile of alectinib was in line with previous reports at the 600 mg BID dose.

Original language	English
Pages (from-to)	217-223
Number of pages	7
Journal	Wspolczesna Onkologia
Volume	27
Issue number	4
DOIs	https://doi.org/10.5114/wo.2023.135246
State	Published - 1 Jan 2023

Keywords

Blood First Assay Screening Trial (BFAST)
NGS
NSCLC
RET fusion
alectinib
blood-based assay
circulating tumour DNA
ctDNA
liquid biopsy
non-small cell lung cancer

ASJC Scopus subject areas

Oncology
Radiology Nuclear Medicine and imaging

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.5114/wo.2023.135246

Cite this

Dziadziuszko, R., Peled, N., Mok, T., Peters, S., Aix, S. P., Alatorre-Alexander, J., Vicuna, B. D., Maclennan, M., Bhagawati-Prasad, V., Shagan, S. M., Schleifman, E., Ruf, T., Mathisen, M. S., & Gadgeel, S. M. (2023). High-dose alectinib for RET fusion-positive non-small cell lung cancer in the Blood First Assay Screening Trial. Wspolczesna Onkologia, 27(4), 217-223. https://doi.org/10.5114/wo.2023.135246

@article{203a76aa651d43c0baa0fd3b22633210,

title = "High-dose alectinib for RET fusion-positive non-small cell lung cancer in the Blood First Assay Screening Trial",

abstract = "Introduction: This paper presents results from Cohort B (rearranged during transfection [RET], fusion-positive) of the Blood First Assay Screening Trial in patients with advanced non-small cell lung cancer (NSCLC) screened for genetic alterations using blood-based next-generation sequencing. Material and methods: Adults with advanced RET fusion-positive NSCLC received alectinib 900 mg twice daily (BID) in Phase I. Enrolment closed prematurely with Phase II uninitiated. Results: Among eight treated patients, confirmed best overall responses in evaluable patients were stable disease (4/5) and progressive disease (1/5). One dose-limiting toxicity (death, unknown cause) was considered by the investigator to be related to treatment and underlying disease. Serious adverse events (SAEs) occurred in five patients, and SAEs that may be related to treatment occurred in two patients. Conclusions: Alectinib showed limited activity in advanced RET fusion-positive NSCLC, and further investigation was not conducted due to the development of selective RET inhibitors pralsetinib and selpercatinib. No new safety signals were observed, and the safety profile of alectinib was in line with previous reports at the 600 mg BID dose.",

keywords = "Blood First Assay Screening Trial (BFAST), NGS, NSCLC, RET fusion, alectinib, blood-based assay, circulating tumour DNA, ctDNA, liquid biopsy, non-small cell lung cancer",

author = "Rafal Dziadziuszko and Nir Peled and Tony Mok and Solange Peters and Aix, {Santiago Ponce} and Jorge Alatorre-Alexander and Vicuna, {Brian D.} and Margaret Maclennan and Vijay Bhagawati-Prasad and Shagan, {Sarah M.} and Erica Schleifman and Thorsten Ruf and Mathisen, {Michael S.} and Gadgeel, {Shirish M.}",

year = "2023",

month = jan,

day = "1",

doi = "10.5114/wo.2023.135246",

language = "English",

volume = "27",

pages = "217--223",

journal = "Wspolczesna Onkologia",

issn = "1428-2526",

publisher = "Termedia Publishing House Ltd.",

number = "4",

}

Dziadziuszko, R, Peled, N, Mok, T, Peters, S, Aix, SP, Alatorre-Alexander, J, Vicuna, BD, Maclennan, M, Bhagawati-Prasad, V, Shagan, SM, Schleifman, E, Ruf, T, Mathisen, MS & Gadgeel, SM 2023, 'High-dose alectinib for RET fusion-positive non-small cell lung cancer in the Blood First Assay Screening Trial', Wspolczesna Onkologia, vol. 27, no. 4, pp. 217-223. https://doi.org/10.5114/wo.2023.135246

TY - JOUR

T1 - High-dose alectinib for RET fusion-positive non-small cell lung cancer in the Blood First Assay Screening Trial

AU - Dziadziuszko, Rafal

AU - Peled, Nir

AU - Mok, Tony

AU - Peters, Solange

AU - Aix, Santiago Ponce

AU - Alatorre-Alexander, Jorge

AU - Vicuna, Brian D.

AU - Maclennan, Margaret

AU - Bhagawati-Prasad, Vijay

AU - Shagan, Sarah M.

AU - Schleifman, Erica

AU - Ruf, Thorsten

AU - Mathisen, Michael S.

AU - Gadgeel, Shirish M.

PY - 2023/1/1

Y1 - 2023/1/1

N2 - Introduction: This paper presents results from Cohort B (rearranged during transfection [RET], fusion-positive) of the Blood First Assay Screening Trial in patients with advanced non-small cell lung cancer (NSCLC) screened for genetic alterations using blood-based next-generation sequencing. Material and methods: Adults with advanced RET fusion-positive NSCLC received alectinib 900 mg twice daily (BID) in Phase I. Enrolment closed prematurely with Phase II uninitiated. Results: Among eight treated patients, confirmed best overall responses in evaluable patients were stable disease (4/5) and progressive disease (1/5). One dose-limiting toxicity (death, unknown cause) was considered by the investigator to be related to treatment and underlying disease. Serious adverse events (SAEs) occurred in five patients, and SAEs that may be related to treatment occurred in two patients. Conclusions: Alectinib showed limited activity in advanced RET fusion-positive NSCLC, and further investigation was not conducted due to the development of selective RET inhibitors pralsetinib and selpercatinib. No new safety signals were observed, and the safety profile of alectinib was in line with previous reports at the 600 mg BID dose.

AB - Introduction: This paper presents results from Cohort B (rearranged during transfection [RET], fusion-positive) of the Blood First Assay Screening Trial in patients with advanced non-small cell lung cancer (NSCLC) screened for genetic alterations using blood-based next-generation sequencing. Material and methods: Adults with advanced RET fusion-positive NSCLC received alectinib 900 mg twice daily (BID) in Phase I. Enrolment closed prematurely with Phase II uninitiated. Results: Among eight treated patients, confirmed best overall responses in evaluable patients were stable disease (4/5) and progressive disease (1/5). One dose-limiting toxicity (death, unknown cause) was considered by the investigator to be related to treatment and underlying disease. Serious adverse events (SAEs) occurred in five patients, and SAEs that may be related to treatment occurred in two patients. Conclusions: Alectinib showed limited activity in advanced RET fusion-positive NSCLC, and further investigation was not conducted due to the development of selective RET inhibitors pralsetinib and selpercatinib. No new safety signals were observed, and the safety profile of alectinib was in line with previous reports at the 600 mg BID dose.

KW - Blood First Assay Screening Trial (BFAST)

KW - NGS

KW - NSCLC

KW - RET fusion

KW - alectinib

KW - blood-based assay

KW - circulating tumour DNA

KW - ctDNA

KW - liquid biopsy

KW - non-small cell lung cancer

UR - http://www.scopus.com/inward/record.url?scp=85186387636&partnerID=8YFLogxK

U2 - 10.5114/wo.2023.135246

DO - 10.5114/wo.2023.135246

M3 - Article

C2 - 38405208

AN - SCOPUS:85186387636

SN - 1428-2526

VL - 27

SP - 217

EP - 223

JO - Wspolczesna Onkologia

JF - Wspolczesna Onkologia

IS - 4

ER -

High-dose alectinib for RET fusion-positive non-small cell lung cancer in the Blood First Assay Screening Trial

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this