Afatinib + Cetuximab versus Afatinib Alone for the First-Line Treatment of EGFR-Mutant NSCLC (SWOG S1403)

Similar progression-free survival and 2-year overall survival rates reported for both treatment groups, with more grade ≥3 treatment-related adverse events reported in the afatinib + cetuximab group.

Although single-agent EGFR tyrosine kinase inhibitor (TKI) therapy is considered standard first-line treatment in patients with EGFR-mutated non–small-cell lung cancer (NSCLC), it is not curative and is associated with a median progression-free survival (PFS) of 10 to 12 months. The combination of afatinib, which is an ErbB family TKI, and the EGFR monoclonal antibody cetuximab has been shown to overcome resistance to EGFR TKIs.¹

SWOG S1403 was a randomized phase 2 trial to evaluate afatinib 40 mg once daily plus cetuximab 500 mg/m² intravenously every 2 weeks versus afatinib alone in patients with EGFR-mutant NSCLC without prior treatment of advanced disease.² The trial was closed at the interim analysis because of insufficient evidence to support accrual; the researchers reported the final results of the trial during the 2020 ASCO Virtual Scientific Program. The primary end point was PFS. Secondary end points included overall response rate, overall survival (OS), and toxicity (as graded by the National Cancer Institute Common Toxicity Criteria version 4.0).²

A total of 168 treatment-naïve patients with EGFR-mutant NSCLC were randomized to receive afatinib + cetuximab (N = 89) or afatinib alone (N = 85).² Patients had stage IV or recurrent NSCLC with a common sensitizing EGFR mutation (exon 19 deletion or L858R point mutation) and had not received prior systemic therapy for advanced or metastatic disease or any prior EGFR TKI.²

Median PFS was comparable between the treatment groups: 11.9 months in the afatinib + cetuximab group versus 13.4 months in the afatinib group (hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.72-1.43; P = .94).² Among the 153 patients with an evaluable assessment, a confirmed or unconfirmed response was reported in 67% of the afatinib + cetuximab group and 74% of the afatinib group (P = .38). The rates of 2-year OS were also similar: 67% in the afatinib + cetuximab group versus 70% in the afatinib group (HR, 0.82; 95% CI, 0.50-1.36; P = .44).²

Grade ≥3 treatment-related adverse events (TRAEs) occurred more frequently in the afatinib + cetuximab group compared with the afatinib group (72% vs 40%); the most frequent grade ≥3 TRAEs were acneiform rash (27% vs 2%), diarrhea (15% vs 20%), and maculopapular rash (13% vs 0%).² Dose reductions of afatinib to 30 mg were more common in patients receiving afatinib + cetuximab compared with those receiving afatinib alone (56.7% vs 26.²%); however, afatinib reductions to 20 mg occurred at similar rates between the treatment groups (13.6% vs 16.7%).²

The researchers concluded that afatinib + cetuximab did not improve clinical outcomes compared with afatinib alone in patients with treatment-naïve, EGFR-mutated NSCLC.²

References
1. Janjigian YY, et al. Cancer Discov. 2014;4:1036-1045.
2. Goldberg SB, et al. J Clin Oncol. 2020;38:4076-4085.