TY - JOUR
T1 - A phase 2 trial combining afatinib with cetuximab in patients with EGFR exon 20 insertion–positive non–small cell lung cancer
AU - van Veggel, Bianca A.M.H.
AU - van der Wekken, Anthonie J.
AU - Paats, Marthe S.
AU - Hendriks, Lizza E.L.
AU - Hashemi, Sayed M.S.
AU - Daletzakis, Antonios
AU - van den Broek, Daan
AU - Bosch, Linda J.W.
AU - Monkhorst, Kim
AU - Smit, Egbert F.
AU - de Langen, Adrianus J.
N1 - Funding Information:
This work was supported by Boehringer Ingelheim and Merck BV, Schiphol-Rijk, the Netherlands, an affiliate of Merck KGaA (CrossRef Funder ID Number 10.13039/100009945). Boehringer Ingelheim had no role in the design, analysis, or interpretation of the study results. Boehringer Ingelheim was given the opportunity to review the manuscript for medical and scientific accuracy as well as intellectual property considerations. Merck KGaA, Darmstadt, Germany, reviewed the manuscript for medical accuracy only before manuscript submission. The authors are fully responsible for the content of this manuscript, and the views and opinions described in the publication reflect solely those of the authors.
Publisher Copyright:
© 2023 American Cancer Society.
PY - 2024/3/1
Y1 - 2024/3/1
N2 - 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.
AB - 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.
KW - afatinib
KW - cetuximab
KW - EGFR exon 20 insertion
KW - non–small cell lung cancer
U2 - 10.1002/cncr.35090
DO - 10.1002/cncr.35090
M3 - Article
SN - 0008-543X
VL - 130
SP - 683
EP - 691
JO - Cancer
JF - Cancer
IS - 5
ER -