Popat, Sanjay;
Januszewski, Adam;
O'Brien, Mary;
Ahmad, Tanya;
Lewanski, Conrad;
Dernedde, Ulrike;
Jankowska, Petra;
... Wilson, William; + view all
(2024)
Long term efficacy of first-line afatinib and the clinical utility of ctDNA monitoring in patients with suspected or confirmed EGFR mutant non-small cell lung cancer who were unsuitable for chemotherapy.
British Journal of Cancer
10.1038/s41416-024-02901-6.
(In press).
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Abstract
BACKGROUND: Here we present long-term outcomes of first line afatinib in comorbid patients with suspected or confirmed EGFR mutant NSCLC otherwise considered unsuitable for chemotherapy, and the clinical utility of serial ctDNA monitoring. METHODS: TIMELY (NCT01415011) was a multicentre, single arm, phase II trial conducted in the UK. Patients aged ≥18 were treated with daily oral afatinib (40 mg) until disease progression or unacceptable toxicity. Blood samples for ctDNA analysis were obtained at baseline and 12-weekly until treatment discontinuation. The primary endpoint was PFS. RESULTS: Thirty-nine patients were enrolled between March 2013 and August 2015. Median follow-up was 98 months (range 69-101). Median PFS was 7.9 months (95% CI 4.6-10.5). Seven patients (18%) continued afatinib beyond 18 months, 3 beyond 36 months and 2 were still on treatment at last follow-up 101 months post-treatment initiation. Analysis of baseline ctDNA samples identified 8 EGFR mutant cases that were not identified by tissue genotyping and ctDNA clearance was associated with improved PFS and OS. CONCLUSION: Afatinib is a viable treatment option for tissue or ctDNA-detected EGFR mutant NSCLC comorbid patients, with a proportion achieving long-term clinical benefit. Plasma ctDNA testing improved EGFR mutant identification and its clearance predicted improved PFS and OS.
| Type: | Article |
|---|---|
| Title: | Long term efficacy of first-line afatinib and the clinical utility of ctDNA monitoring in patients with suspected or confirmed EGFR mutant non-small cell lung cancer who were unsuitable for chemotherapy. |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41416-024-02901-6 |
| Publisher version: | https://doi.org/10.1038/s41416-024-02901-6 |
| Language: | English |
| Additional information: | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > CRUK Cancer Trials Centre |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10202697 |
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