Randomized Trial of Afatinib Plus Cetuximab Versus Afatinib Alone for First-Line Treatment of EGFR-Mutant Non–Small-Cell Lung Cancer: Final Results From SWOG S1403

Author:

Goldberg Sarah B.1,Redman Mary W.2,Lilenbaum Rogerio1,Politi Katerina1,Stinchcombe Thomas E.3,Horn Leora4,Chen Everett H.5,Mashru Sandeep H.6,Gettinger Scott N.1,Melnick Mary Ann1,Herbst Roy S.1,Baumgart Megan A.7,Miao Jieling2,Moon James2,Kelly Karen8,Gandara David R.8

Affiliation:

1. Yale School of Medicine, New Haven, CT

2. SWOG Statistical Center, Seattle, WA

3. Duke Cancer Center, Durham, NC

4. Vanderbilt-Ingram Cancer Center, Nashville, TN

5. Kaiser Permanente Medical Group/NCORP, Bellflower CA

6. Kaiser Permanente Medical Group/NCORP, Portland, OR

7. University of Rochester Medical Center, Rochester, NY

8. UC Davis Comprehensive Cancer Center, Sacramento, CA

Abstract

PURPOSE The irreversible ErbB family tyrosine kinase inhibitor (TKI) afatinib plus the EGFR monoclonal antibody cetuximab was previously shown to overcome resistance to EGFR TKIs. We studied whether the combination of afatinib plus cetuximab compared with afatinib alone would improve progression-free survival (PFS) in patients with treatment-naive EGFR-mutant non–small-cell lung cancer (NSCLC) by preventing or delaying resistance. METHODS Patients with EGFR-mutant NSCLC without prior treatment of advanced disease were enrolled in this phase II, multicenter trial and randomly assigned to receive afatinib 40 mg orally daily plus cetuximab 500 mg/m2 intravenously every 2 weeks or afatinib alone. The primary end point was PFS. RESULTS Between March 25, 2015 and April 23, 2018, 174 patients were randomly assigned, and 168 (83 on afatinib + cetuximab and 85 on afatinib) were eligible. There was no improvement in PFS in patients receiving afatinib plus cetuximab compared with afatinib alone (hazard ratio [HR], 1.01; 95% CI, 0.72 to 1.43; P = .94; median, 11.9 months v 13.4 months). Similarly, there was no difference in response rate (67% v 74%; P = .38) or overall survival (HR, 0.82; 95% CI, 0.50 to 1.36; P = .44). Toxicity was greater with the combination: grade ≥ 3 adverse events related to treatment occurred in 72% of patients receiving afatinib plus cetuximab compared with 40% of those receiving afatinib alone, most commonly rash and diarrhea. Dose reductions were more common in patients receiving the combination, and 30% of patients in this arm discontinued cetuximab due to toxicity. At interim analysis, there was insufficient evidence to support continued accrual, and the trial was closed. CONCLUSIONS The addition of cetuximab to afatinib did not improve outcomes in previously untreated EGFR-mutant NSCLC, despite recognized activity in the acquired resistance setting.

Publisher

American Society of Clinical Oncology (ASCO)

Subject

Cancer Research,Oncology

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