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Research Article
Motohiro Tamiya
Osaka International Cancer Institute
Corresponding Author
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Background: Afatinib followed by osimertinib (Afa group) may reportedly provide better outcomes for T790M-positive non-small cell lung cancer (NSCLC) than 1st-generation (G) epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) (1st-G group).
Methods: We studied 111 consecutive patients with T790M mutation-positive NSCLC who were treated with osimertinib after progression following 1st- or 2nd-G EGFR-TKI between March 28, 2016 and March 31, 2018. We analyzed T790M ratio with the re-biopsy tissue, obtained after EGFR-TKI resistance using droplet digital polymerase chain reaction, and investigate whether afatinib prifies the T790M mutation more than 1st-G EGFR-TKI.
Results: Among the 60 patients with preserved re-biopsy tissues, we analyzed 38 patients whose re-biopsy tissue had adequate DNA content. Eleven patients in the Afa group had 81.8% of response rate, and 27 patients in the 1st-G group had 85.2% with RR. The mean T790M ratio was 0.3643. The T790M ratio in those with response of the osimertinib group was significantly higher than in those with non-response group (p=0.0272) and was similar in the Afa and 1st-G group (p=0.9693).
Conclusion: T790M ratio significantly correlated with osimertinib response and T790M ratio was similar between the 1st and 2nd -G EGFR-TKIs in 1st or 2nd -G EGFR-TKI-refractory tumors.
Keywords
Osimertinib, T790M, EGFR-TKI, refractory NSCLC, droplet digital PCR
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Competing interest reported. Motohiro Tamiya has research grant from Boehringer Ingelheim and lecture fee from Boehringer Ingelheim, Chugai Pharmaceutical, and AstraZeneca. Akihiro Tamiya has research grant from AstraZeneca and lecture fee from Boehringer Ingelheim, Chugai Pharmaceutical, and AstraZeneca. Yoshihiko Taniguchi has lecture fee from AstraZeneca. Kazuo Nishino has research grant from Boehringer Ingelheim and lecture fee from Boehringer Ingelheim, Chugai Pharmaceutical, and AstraZeneca. Fumio Imamura has research grant from AstraZeneca. Other authors have no conflicts of interest to declare under consideration for publication.
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This preprint is under consideration at Scientific Reports. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
Motohiro Tamiya
Osaka International Cancer Institute
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 10 Feb, 2021
No community comments so far
Editorial decision: Major revision
On 25 Feb, 2021
Reviews received
Received 25 Feb, 2021
Reviews received
Received 24 Feb, 2021
Reviewers agreed
On 24 Feb, 2021
Reviewers agreed
On 23 Feb, 2021
Reviewers invited
Invitations sent on 23 Feb, 2021
Editor assigned
On 18 Feb, 2021
Editor invited
On 11 Feb, 2021
Submission checks complete
On 08 Feb, 2021
First submitted
On 24 Jan, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Afatinib followed by osimertinib (Afa group) may reportedly provide better outcomes for T790M-positive non-small cell lung cancer (NSCLC) than 1st-generation (G) epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) (1st-G group).
Methods: We studied 111 consecutive patients with T790M mutation-positive NSCLC who were treated with osimertinib after progression following 1st- or 2nd-G EGFR-TKI between March 28, 2016 and March 31, 2018. We analyzed T790M ratio with the re-biopsy tissue, obtained after EGFR-TKI resistance using droplet digital polymerase chain reaction, and investigate whether afatinib prifies the T790M mutation more than 1st-G EGFR-TKI.
Results: Among the 60 patients with preserved re-biopsy tissues, we analyzed 38 patients whose re-biopsy tissue had adequate DNA content. Eleven patients in the Afa group had 81.8% of response rate, and 27 patients in the 1st-G group had 85.2% with RR. The mean T790M ratio was 0.3643. The T790M ratio in those with response of the osimertinib group was significantly higher than in those with non-response group (p=0.0272) and was similar in the Afa and 1st-G group (p=0.9693).
Conclusion: T790M ratio significantly correlated with osimertinib response and T790M ratio was similar between the 1st and 2nd -G EGFR-TKIs in 1st or 2nd -G EGFR-TKI-refractory tumors.
Figure 1
Figure 2
Figure 3
Figure 4
Competing interest reported. Motohiro Tamiya has research grant from Boehringer Ingelheim and lecture fee from Boehringer Ingelheim, Chugai Pharmaceutical, and AstraZeneca. Akihiro Tamiya has research grant from AstraZeneca and lecture fee from Boehringer Ingelheim, Chugai Pharmaceutical, and AstraZeneca. Yoshihiko Taniguchi has lecture fee from AstraZeneca. Kazuo Nishino has research grant from Boehringer Ingelheim and lecture fee from Boehringer Ingelheim, Chugai Pharmaceutical, and AstraZeneca. Fumio Imamura has research grant from AstraZeneca. Other authors have no conflicts of interest to declare under consideration for publication.
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