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.
Sanjay Popat, Adam Januszewski, Mary O'Brien, Tanya Ahmad, Conrad Lewanski, Ulrike Dernedde, Petra Jankowska, Clive Mulatero, Riyaz Shah, Jonathan Hicks, Tom Geldart, Mathilda Cominos, Gill Gray, James Spicer, Karen Bell, Simon Roitt, Clive Morris, Yenting Ngai, Laura Hughes, Allan Hackshaw, William Wilson
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引用次数: 0
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.
期刊介绍:
The British Journal of Cancer is one of the most-cited general cancer journals, publishing significant advances in translational and clinical cancer research.It also publishes high-quality reviews and thought-provoking comment on all aspects of cancer prevention,diagnosis and treatment.