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

• Published in: Cancer Vol. 130; no. 5; pp. 683 - 691
• Main Authors: Veggel, Bianca A. M. H., Wekken, Anthonie J., Paats, Marthe S., Hendriks, Lizza E. L., Hashemi, Sayed M. S., Daletzakis, Antonios, Broek, Daan, Bosch, Linda J. W., Monkhorst, Kim, Smit, Egbert F., Langen, Adrianus J.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.03.2024
• Subjects: afatinib; Anticancer properties; Antitumor activity; cetuximab; Diarrhea; Disease control; EGFR exon 20 insertion; Epidermal growth factor receptors; Erythema; Growth factors; Insertion; Kinases; Lung cancer; Monoclonal antibodies; Mutation; Non-small cell lung carcinoma; non–small cell lung cancer; Small cell lung carcinoma; Survival; Toxicity; Tyrosine; Tyrosine kinase inhibitors; non-small cell lung cancer; afatinib; cetuximab; EGFR exon 20 insertion
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.35090

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. Combination treatment with afatinib and cetuximab in patients with non–small cell lung cancer harboring an EGFR exon 20 insertion mutation demonstrated antitumor activity with a disease control rate of 54% at 18 weeks of treatment and a 32% confirmed overall response rate.