Phase II Study of Low-Dose Afatinib Maintenance Treatment Among Patients with EGFR-Mutated Non-Small Cell Lung Cancer: North Japan Lung Cancer Study Group Trial 1601 (NJLCG1601).
Journal
The oncologist
ISSN: 1549-490X
Titre abrégé: Oncologist
Pays: England
ID NLM: 9607837
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
31
03
2020
accepted:
31
05
2020
pubmed:
20
6
2020
medline:
22
6
2021
entrez:
20
6
2020
Statut:
ppublish
Résumé
Low-dose afatinib maintenance treatment among patients with EGFR-mutated NSCLC achieved long-time to treatment failure with fewer treatment-related AEs without detracting from the therapeutic efficacy. This modified regimen represents a practical usage that balances effectiveness and safety. Although afatinib is an effective therapy for patients with EGFR-mutated non-small cell lung cancer (NSCLC), drug-related adverse events (AEs) have often necessitated dose reductions. In a post hoc analysis of the LUX-Lung 3 and 6 trials, there was no difference in median progression-free survival (PFS) between patients who had the dose of afatinib reduced and those who did not. We thus evaluated the efficacy and tolerability of low-dose afatinib maintenance treatment among patients with NSCLC harboring EGFR mutations who had not been previously treated. Eligible patients received afatinib 40 mg orally once daily. When prescribed grade ≥ 2 AEs, rash of grade ≥ 3, or unacceptable toxicity occurred, the afatinib dose was reduced from 40 to 30 mg and if needed from 30 to 20 mg. The primary endpoint was the 1-year PFS rate. Secondary endpoints were PFS, overall response rate (ORR), and toxicity. Among 30 patients, 93% had adenocarcinoma, 53% had exon 19 deletion, 37% had L858R, and 10% had minor mutations. The 1-year PFS rate was 50% (95% confidence interval [CI], 31.3-66.1) and the median PFS was 11.8 months (95% CI, 7.1-21.4). The incidence rate of grade ≥ 3 toxicities was 57%, including elevated aspartate aminotransferase/alanine aminotransferase level (13%), diarrhea (10%), and paronychia (10%). Low-dose afatinib maintenance treatment reduced treatment-related AEs without detracting from the therapeutic efficacy.
Sections du résumé
LESSONS LEARNED
Low-dose afatinib maintenance treatment among patients with EGFR-mutated NSCLC achieved long-time to treatment failure with fewer treatment-related AEs without detracting from the therapeutic efficacy. This modified regimen represents a practical usage that balances effectiveness and safety.
BACKGROUND
Although afatinib is an effective therapy for patients with EGFR-mutated non-small cell lung cancer (NSCLC), drug-related adverse events (AEs) have often necessitated dose reductions. In a post hoc analysis of the LUX-Lung 3 and 6 trials, there was no difference in median progression-free survival (PFS) between patients who had the dose of afatinib reduced and those who did not. We thus evaluated the efficacy and tolerability of low-dose afatinib maintenance treatment among patients with NSCLC harboring EGFR mutations who had not been previously treated.
METHODS
Eligible patients received afatinib 40 mg orally once daily. When prescribed grade ≥ 2 AEs, rash of grade ≥ 3, or unacceptable toxicity occurred, the afatinib dose was reduced from 40 to 30 mg and if needed from 30 to 20 mg. The primary endpoint was the 1-year PFS rate. Secondary endpoints were PFS, overall response rate (ORR), and toxicity.
RESULTS
Among 30 patients, 93% had adenocarcinoma, 53% had exon 19 deletion, 37% had L858R, and 10% had minor mutations. The 1-year PFS rate was 50% (95% confidence interval [CI], 31.3-66.1) and the median PFS was 11.8 months (95% CI, 7.1-21.4). The incidence rate of grade ≥ 3 toxicities was 57%, including elevated aspartate aminotransferase/alanine aminotransferase level (13%), diarrhea (10%), and paronychia (10%).
CONCLUSION
Low-dose afatinib maintenance treatment reduced treatment-related AEs without detracting from the therapeutic efficacy.
Identifiants
pubmed: 32559335
doi: 10.1634/theoncologist.2020-0545
pmc: PMC7543297
doi:
Substances chimiques
Protein Kinase Inhibitors
0
Quinazolines
0
Afatinib
41UD74L59M
EGFR protein, human
EC 2.7.10.1
ErbB Receptors
EC 2.7.10.1
Types de publication
Clinical Trial, Phase II
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1451-e1456Informations de copyright
© AlphaMed Press; the data published online to support this summary are the property of the authors.
Références
N Engl J Med. 2010 Jun 24;362(25):2380-8
pubmed: 20573926
Ann Oncol. 2016 Nov;27(11):2103-2110
pubmed: 27601237
Lancet Oncol. 2010 Feb;11(2):121-8
pubmed: 20022809
Lancet Oncol. 2014 Feb;15(2):213-22
pubmed: 24439929
Oncogene. 2008 Aug 7;27(34):4702-11
pubmed: 18408761
Cancer Sci. 2011 May;102(5):1032-7
pubmed: 21272159
Ann Oncol. 2017 Feb 1;28(2):270-277
pubmed: 28426106
Future Oncol. 2018 Nov;14(27):2861-2874
pubmed: 30336693
J Clin Oncol. 2013 Sep 20;31(27):3327-34
pubmed: 23816960
Lancet Oncol. 2015 Jul;16(7):830-8
pubmed: 26051236
N Engl J Med. 2020 Jan 2;382(1):41-50
pubmed: 31751012
Cancer Sci. 2015 Sep;106(9):1202-11
pubmed: 26094656
Lancet. 2017 Jan 21;389(10066):299-311
pubmed: 27574741
J Pharmacol Exp Ther. 2012 Nov;343(2):342-50
pubmed: 22888144
Lancet Oncol. 2015 Feb;16(2):141-51
pubmed: 25589191