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Clinical Trial
. 2024 Mar 1;130(5):683-691.
doi: 10.1002/cncr.35090. Epub 2023 Oct 31.

A phase 2 trial combining afatinib with cetuximab in patients with EGFR exon 20 insertion-positive non-small cell lung cancer

Bianca A M H van Veggel  1 , Anthonie J van der Wekken  2 , Marthe S Paats  3 , Lizza E L Hendriks  4 , Sayed M S Hashemi  5 , Antonios Daletzakis  6 , Daan van den Broek  7 , Linda J W Bosch  8 , Kim Monkhorst  8 , Egbert F Smit  1   9 , Adrianus J de Langen  1
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Free article
Clinical Trial

A phase 2 trial combining afatinib with cetuximab in patients with EGFR exon 20 insertion-positive non-small cell lung cancer

Bianca A M H van Veggel et al. Cancer. .
Free article

Abstract

Background: Epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations are the third most common EGFR mutations in patients with non-small cell lung cancer (NSCLC) and are associated with primary resistance to EGFR tyrosine kinase inhibitors (TKIs). There is evidence of activity of combining EGFR TKIs with monoclonal antibodies. This study reports on the efficacy and safety of afatinib in combination with cetuximab.

Methods: In this single-arm phase 2 trial, patients with advanced NSCLC harboring an EGFR ex20ins mutation were treated with afatinib 40 mg once daily in combination with cetuximab 500 mg/m2 every 2 weeks. The primary end point was disease control rate (DCR) at 18 weeks of treatment.

Results: Thirty-seven patients started treatment, with a median age of 65 years (range, 40-80 years), 78% female, and 95% White. The study achieved its primary end point with a DCR of 54% at 18 weeks, an overall response rate (ORR) of 43%, and a 32% confirmed ORR. Best responses were partial (n = 16), stable (n = 16), progressive disease (n = 2), or not evaluable (n = 3). Median progression-free survival was 5.5 months (95% CI, 3.7-8.3 months) and median overall survival was 16.8 months (95% CI, 10.7-25.8 months). The most common treatment-related adverse events (TRAEs) were diarrhea (70%), rash (65%), dry skin (59%), paronychia (54%), and erythema (43%). Grade 3 TRAEs were reported in 54% of all patients.

Conclusions: Combination treatment with afatinib and cetuximab demonstrated antitumor activity with a DCR of 54% at 18 weeks and a 32% confirmed ORR. Toxicity was significant, although manageable, after dose reduction.

Keywords: EGFR exon 20 insertion; afatinib; cetuximab; non-small cell lung cancer.

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References

REFERENCES

    1. Beau-Faller M, Prim N, Ruppert AM, et al. Rare EGFR exon 18 and exon 20 mutations in non-small-cell lung cancer on 10 117 patients: a multicentre observational study by the French ERMETIC-IFCT network. Ann Oncol. 2014;25(1):126-131. doi:10.1093/annonc/mdt418
    1. Fang W, Huang Y, Hong S, et al. EGFR exon 20 insertion mutations and response to osimertinib in non-small-cell lung cancer. BMC Cancer. 2019;19(1):595. doi:10.1186/s12885-019-5820-0
    1. Kosaka T, Tanizaki J, Paranal RM, et al. Response heterogeneity of EGFR and HER2 exon 20 insertions to covalent EGFR and HER2 inhibitors. Cancer Res. 2017;77(10):2712-2721. doi:10.1158/0008-5472.can-16-3404
    1. Riess JW, Gandara DR, Frampton GM, et al. Diverse EGFR exon 20 insertions and co-occurring molecular alterations identified by comprehensive genomic profiling of NSCLC. J Thorac Oncol. 2018;13(10):1560-1568. doi:10.1016/j.jtho.2018.06.019
    1. Naidoo J, Sima CS, Rodriguez K, et al. Epidermal growth factor receptor exon 20 insertions in advanced lung adenocarcinomas: clinical outcomes and response to erlotinib. Cancer. 2015;121(18):3212-3220. doi:10.1002/cncr.29493

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