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Multicenter Study
. 2015 Oct;20(10):1167-74.
doi: 10.1634/theoncologist.2015-0073. Epub 2015 Sep 9.

Afatinib in Non-Small Cell Lung Cancer Harboring Uncommon EGFR Mutations Pretreated With Reversible EGFR Inhibitors

David F Heigener  1 , Christian Schumann  2 , Martin Sebastian  3 , Parvis Sadjadian  4 , Ingo Stehle  5 , Angela Märten  6 , Anne Lüers  7 , Frank Griesinger  7 , Matthias Scheffler  8 ; Afatinib Compassionate Use Consortium (ACUC)
Collaborators, Affiliations
Multicenter Study

Afatinib in Non-Small Cell Lung Cancer Harboring Uncommon EGFR Mutations Pretreated With Reversible EGFR Inhibitors

David F Heigener et al. Oncologist. 2015 Oct.

Abstract

Background: Afatinib, an irreversible ErbB family blocker, is approved for treatment of patients with previously untreated non-small cell lung cancer (NSCLC) harboring activating epidermal growth factor receptor (EGFR) mutations. Efficacy of afatinib in EGFR tyrosine kinase inhibitor-naïve (TKI-naïve) patients with uncommon EGFR mutations (other than exon 19 deletions or exon 21 point mutations) has been reported; however, efficacy in TKI-pretreated patients with uncommon EGFR mutations is unknown.

Materials and methods: In the afatinib compassionate use program (CUP), patients with advanced or metastatic, histologically confirmed NSCLC progressing after at least one line of chemotherapy and one line of EGFR-TKI treatment were enrolled. Demographic data, mutation type, response rates, time to treatment failure (TTF), and safety in patients harboring uncommon EGFR mutations were reported.

Results: In 60 patients (63% female, median age 63 years [range: 30-84 years]), a total of 66 uncommon EGFR mutations including 30 T790M mutations were reported (18.4% and 11%, respectively, of known EGFR mutations within the CUP). Most patients (67%) received afatinib as third- or fourth-line treatment. Median TTF was 3.8 months (range: 0.2 to >24.6 months; p = .244) in patients with uncommon mutations compared with 5.1 months (range: 0.1 to >21.1 months) in patients with common mutations (n = 165). Pronounced activity was observed with E709X mutations (TTF >12 months). No new safety signals were detected.

Conclusion: Afatinib is clinically active and well tolerated in many TKI-pretreated NSCLC patients harboring uncommon EGFR mutations. Compared with results reported in TKI-naïve patients, activity was also indicated in patients with T790M and exon 20 insertion mutations.

Keywords: Afatinib; Compassionate use trials; Epidermal growth factor receptor; ErbB receptors; Non-small cell lung cancer.

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Conflict of interest statement

Disclosures of potential conflicts of interest may be found at the end of this article.

Figures

Figure 1.
Figure 1.
Distribution of the 60 rare EGFR mutations. Abbreviation: incl., including.
Figure 2.
Figure 2.
Time to treatment failure of common and uncommon EGFR mutations.
See this image and copyright information in PMC

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