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

2020 Year in Review - Non–Small-Cell Lung Cancer - Lung Cancer

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.

Related Items
Third-Line Tyrosine Kinase Inhibitor Therapy Results in 16-Year Remission in a Patient with Stage IV Non–Small-Cell Lung Cancer
JHOP - August 2022 Vol 12, No 4 published on August 22, 2022 in Case Reports, Lung Cancer
2022 Midyear Review: Non–Small-Cell Lung Cancer
JHOP - Supplements published on July 21, 2022 in Lung Cancer
First-Line Sotorasib Shows Long-Lasting Responses in Metastatic NSCLC with KRAS Mutation
JHOP - June 2022 Vol 12, No 3 published on June 16, 2022 in AACR Highlights, Lung Cancer
Opdivo plus Platinum-Based Chemotherapy FDA Approved as First Neoadjuvant Treatment in Early-Stage NSCLC
JHOP - April 2022 Vol 12, No 2 published on May 3, 2022 in FDA Oncology Update, Lung Cancer, Checkpoint Inhibitors
Severe Adverse Events from Immune Checkpoint Inhibitor Therapy a Rare Concerning Side Effect
2021 Year in Review - Non–Small-Cell Lung Cancer published on December 29, 2021 in Lung Cancer
KRASᴳ¹²ᶜ Mutation–Positive Advanced NSCLC
2021 Year in Review - Non–Small-Cell Lung Cancer published on December 29, 2021 in Lung Cancer
CodeBreaK 100 Trial Results Demonstrate Sotorasib Conveys Clinical Benefit Across NSCLC Patient Subgroups
2021 Year in Review - Non–Small-Cell Lung Cancer published on December 29, 2021 in Lung Cancer
NSAID Use with Immune Checkpoint Inhibitors Associated with Longer Overall Survival in NSCLC
2021 Year in Review - Non–Small-Cell Lung Cancer published on December 29, 2021 in Lung Cancer
The Effect of Various KRAS Mutations on NSCLC Susceptibility
2021 Year in Review - Non–Small-Cell Lung Cancer published on December 29, 2021 in Lung Cancer
Patterns of Biomarker Testing in Metastatic NSCLC in the Community Oncology Setting
2021 Year in Review - Non–Small-Cell Lung Cancer published on December 29, 2021 in Lung Cancer
© Amplity Health. All rights reserved.

Subscribe Today!

To sign up for our newsletter or print publications, please enter your contact information below.

I'd like to receive: