TY - JOUR
T1 - Clinical utility of liquid biopsy for EGFR driver, T790M mutation and EGFR amplification in plasma in patients with acquired resistance to afatinib
AU - Oya, Yuko
AU - Yoshida, Tatsuya
AU - Asada, Kazuhiro
AU - Oguri, Tetsuya
AU - Inui, Naoki
AU - Morikawa, Sayako
AU - Ito, Kentaro
AU - Kimura, Tomoki
AU - Kunii, Eiji
AU - Matsui, Takashi
AU - Kubo, Akihito
AU - Kato, Tatsuo
AU - Abe, Takashi
AU - Tsuda, Takeshi
AU - Hida, Toyoaki
N1 - Funding Information:
This research was supported by grants from Nippon Boehringer Ingelheim for the enrollment of patients and analyzing EGFR mutation in plasma, and the Aichi Cancer Research Foundation for the retrospective study.
Funding Information:
The authors would like to thank the following companies for their contributions: SRL Inc., Tokyo, Japan, and G&G Science Inc., Fukushima, Japan for the analysis of cfDNA.
Funding Information:
Dr. Yoshida has obtained research grants from Nippon Boehringer Ingelheim. Dr. Hida has obtained research grants from Novartis Pharma, Chugai Pharmaceutical, Taiho Pharmaceutical, AstraZeneca, Nippon Boehringer Ingelheim, Pfizer, Janssen Pharmaceutical, and Astellas, and has received personal fees from Novartis Pharma, Chugai Pharmaceutical, Taiho Pharmaceutical, AstraZeneca, Nippon Boehringer Ingelheim, and Pfizer. Dr. Ito has obtained personal fees from Nippon Boehringer Ingelheim, AstraZeneca, Pfizer, Eli Lilly, Chugai Pharmaceutical, MSD, Ono Pharmaceutical, Taiho Pharmaceutical. All the other authors have no conflicts of interest. Dr. Ogutri has obtained research grant from Nippon Boehringer Ingelheim and speaker’s bureau from Chugai Pharmaceutical, Taiho Pharmaceutical, Boehringer Ingelheim, AstraZeneca, Eli Lilly. Dr. Kimura has obtained speaker’s bureau from Chugai Pharmaceutical, Taiho Pharmaceutical, Boehringer Ingelheim, AstraZeneca, Novartis Pharma, Meiji Seika Pharmaceutical, MSD, Kyorin Pharmaceutical, Ono Pharmaceutical. Dr. Kubo has obtained honoraria from Boehringer Ingelheim.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - Background: Cell-free DNA (cfDNA) genotyping in plasma using the cobas EGFR Mutation Test v2 (cobas) is the first liquid biopsy as a companion diagnosis to identify the EGFR T790M mutation (T790M) after the failure of treatment of EGFR-tyrosine kinase inhibitors (TKIs) (1st generation, gefitinib [G] and erlotinib [E] and 2nd generation, afatinib [A]). This study investigated the clinical utility of a liquid biopsy for patients who acquired resistance to afatinib. Methods: We prospectively collected plasma from 51 patients who had acquired resistance to afatinib between April 2015 and November 2016 to evaluate the frequency of T790M by cobas and digital droplet PCR (UMIN000025112). Additionally, we retrospectively reviewed 38 patients who tested by cobas in plasma after G/E failure to compare for T790M detection between A and with G/E. Results: The detection rate of EGFR-driver and T790M in plasma in patients treated with A (A group) as a first-line EGFR-TKI was lower than with G/E followed by A (G/E→A group), although the differences were not significant (EGFR-driver: 41% [A] vs. 67% [G/E→A], P=0.1867; and T790M: 8% [A] vs. 17% [G/E→A], P=0.5798). In first-line setting, the detection rate for EGFR-driver and T790M in plasma by cobas was lower in A group than in G/E group, although there was no significant difference (EGFR-driver: 34% [A] vs. 52% [G/E], P=0.2072; and T790M: 10% [A] vs. 27% [G/E], P=0.1161). Conclusion: The detection of EGFR-driver and T790M in plasma by cobas in patients treated with afatinib might be lower than with G/E in a real-world setting.
AB - Background: Cell-free DNA (cfDNA) genotyping in plasma using the cobas EGFR Mutation Test v2 (cobas) is the first liquid biopsy as a companion diagnosis to identify the EGFR T790M mutation (T790M) after the failure of treatment of EGFR-tyrosine kinase inhibitors (TKIs) (1st generation, gefitinib [G] and erlotinib [E] and 2nd generation, afatinib [A]). This study investigated the clinical utility of a liquid biopsy for patients who acquired resistance to afatinib. Methods: We prospectively collected plasma from 51 patients who had acquired resistance to afatinib between April 2015 and November 2016 to evaluate the frequency of T790M by cobas and digital droplet PCR (UMIN000025112). Additionally, we retrospectively reviewed 38 patients who tested by cobas in plasma after G/E failure to compare for T790M detection between A and with G/E. Results: The detection rate of EGFR-driver and T790M in plasma in patients treated with A (A group) as a first-line EGFR-TKI was lower than with G/E followed by A (G/E→A group), although the differences were not significant (EGFR-driver: 41% [A] vs. 67% [G/E→A], P=0.1867; and T790M: 8% [A] vs. 17% [G/E→A], P=0.5798). In first-line setting, the detection rate for EGFR-driver and T790M in plasma by cobas was lower in A group than in G/E group, although there was no significant difference (EGFR-driver: 34% [A] vs. 52% [G/E], P=0.2072; and T790M: 10% [A] vs. 27% [G/E], P=0.1161). Conclusion: The detection of EGFR-driver and T790M in plasma by cobas in patients treated with afatinib might be lower than with G/E in a real-world setting.
UR - http://www.scopus.com/inward/record.url?scp=85099307896&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85099307896&partnerID=8YFLogxK
U2 - 10.1186/s12885-020-07777-2
DO - 10.1186/s12885-020-07777-2
M3 - Article
C2 - 33435905
AN - SCOPUS:85099307896
VL - 21
JO - BMC Cancer
JF - BMC Cancer
SN - 1471-2407
IS - 1
M1 - 57
ER -