As reported in the Journal of Clinical Oncology by Sarah B. Goldberg, MD, MPH, and colleagues, final results of the phase II SWOG S1403 trial show no progression-free survival benefit with afatinib plus cetuximab vs afatinib alone in the first-line treatment of EGFR-mutant advanced non–small cell lung cancer (NSCLC).
Sarah B. Goldberg, MD, MPH
As stated by the investigators, “The irreversible ErbB family tyrosine kinase inhibitor afatinib plus the EGFR monoclonal antibody cetuximab was previously shown to overcome resistance to EGFR tyrosine kinase inhibitors. We studied whether the combination of afatinib plus cetuximab compared with afatinib alone would improve progression-free survival in patients with treatment-naive EGFR-mutant NSCLC by preventing or delaying resistance.”
Study Details
In the multicenter trial, 168 eligible patients were randomly assigned between March 2015 and April 2018 to receive afatinib at 40 mg daily plus cetuximab at 500 mg/m2 every 2 weeks (n = 83) or afatinib alone (n = 85). 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 tyrosine kinase inhibitor. The primary endpoint was progression-free survival.
Key Findings
Upon review of the interim analysis of the trial (April 2018), the SWOG data safety and monitoring committee determined that there was insufficient evidence to support continued accrual, and the trial was closed.
There was no improvement in progression-free survival with the combination vs afatinib alone (median = 11.9 months vs 13.4 months, hazard ratio [HR] = 1.01, 95% confidence interval [CI] = 0.72–1.43; P = .94). Subset analyses showed no differences between groups regardless of clinical or tumor characteristics.
Among 153 patients who had baseline measurable disease, no difference in objective response rate was observed (67% vs 74%, P = .38).
No significant difference in overall survival was observed (HR = 0.82, 95% CI = 0.50–1.36; P = .44), with 2-year rates of 67% vs 70%.
Toxicity was greater with the combination. Treatment-related grade ≥ 3 adverse events occurred in 72% of the combination group vs 40% of the afatinib group, with the most common being rash (maculopapular and acneiform; 40% vs 2%) and diarrhea (15% vs 20%). Cetuximab was discontinued in 30% of patients due to toxicity.
The investigators concluded, “The addition of cetuximab to afatinib did not improve outcomes in previously untreated EGFR-mutant NSCLC, despite recognized activity in the acquired resistance setting.”
Dr. Goldberg, of Yale School of Medicine, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by grants from the National Cancer Institute, Boehringer Ingelheim Pharmaceuticals, Eli Lilly, and others. For full disclosures of the study authors, visit ascopubs.org.
