Retreatment with erlotinib: Regain of TKI sensitivity following a drug holiday for patients with NSCLC who initially responded to EGFR-TKI treatment
Abstract
Background Tyrosine kinase inhibitors (TKI) of the epidermal growth factor receptor (EGFR) are approved as treatment of non-small-cell lung cancer (NSCLC). Despite an initially impressive response to EGFR-TKIs, patients with an activating EGFR mutation invariably relapse. For these patients few treatment options are available after additional progression during or after chemotherapy. The aim of this study is to examine the effect of retreatment with an EGFR-TKI after a drug holiday.Patients and methods We retrospectively reviewed the medical records of 14 patients with stage IV NSCLC who progressed after long-term disease control with EGFR-TKI, who were subsequently treated with standard chemotherapy and at renewed progression retreated with EGFR-TKI.Results Fourteen patients (five male, nine female, median age 55 years (39-70 years) received retreatment with erlotinib. The median interval from the discontinuation of EGFR-TKI to the 2nd episode was 9.5 months (3-36 months). Before starting retreatment 36% (n=5) had a T790M mutation. Retreatment resulted in 36% (n=5) partial response, 50% stable disease (n=7) and 14% progressive disease (n=2). Among patients with a T790M mutation this number was two, one and two, respectively. Seven patients are still on therapy without signs of progression. Median follow up is 9 months (1.5-16+months) and median PFS is 6.5 months (1-16+months).Conclusion Our findings suggest that retreatment with erlotinib is an option for patients with NSCLC who initially benefited from previous EGFR-TKI treatment and progressed after standard cytotoxic chemotherapy.
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Discontinuous dosing of the drug could be a strategy to prevent or retard acquired resistance.
“the lessons learned from metronomic treatment strategies for BRAF V600E melanomas as well as EGFR-mutant NSCLCs suggest that discontinuous dosing of the drug could be a strategy to prevent or retard acquired resistance [138, 139].”
From Primary and acquired resistance to EGFR-targeted therapies in colorectal cancer: impact on future treatment strategies (2014) · cites this paper as [139]
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- Authors
- Becker, A., Crombag, L., Heideman, D. A. M., Thunnissen, F. B., van Wijk, A. W., Postmus, P. E., & Smit, E. F.
- Affiliations
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
- Venue
- European Journal of Cancer
- Publisher
- Elsevier BV
- Published
- 2011-11
- Volume
- 47
- Issue
- 17
- Pages
- 2603-2606
- ISSN
- 0959-8049 (ISSN-L)
- OpenAlex
- W2166261313
- Cited by
- 117
- References
- 16
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 4 · 2023: 5 · 2022: 6 · 2021: 5 · 2020: 6 · 2019: 2 · 2018: 4 · 2017: 11 · 2016: 13 · 2015: 9 · 2014: 15 · 2013: 21 · 2012: 9
- FWCI
- 12.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Cancer (publishedVersion)
- PubMed (publishedVersion)
- Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
- Keywords
- erlotinib, EGFR tyrosine kinase inhibitors, non-small cell lung cancer, drug holidays, retreatment, T790M mutation, EGFR mutation, acquired drug resistance, tyrosine kinase inhibitor sensitivity
- MeSH terms
- Erlotinib Hydrochloride, Adult, Aged, Antineoplastic Agents, Carcinoma, Non-Small-Cell Lung, DNA Mutational Analysis, Female, Humans, Lung Neoplasms, Male, Middle Aged, Mutation, Quinazolines, Retrospective Studies, Retreatment, Protein Kinase Inhibitors, ErbB Receptors
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