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 - PubMed (original) (raw)

Clinical Trial

. 2020 Dec 1;38(34):4076-4085.

doi: 10.1200/JCO.20.01149. Epub 2020 Oct 6.

Mary W Redman 2, Rogerio Lilenbaum 1, Katerina Politi 1, Thomas E Stinchcombe 3, Leora Horn 4, Everett H Chen 5, Sandeep H Mashru 6, Scott N Gettinger 1, Mary Ann Melnick 1, Roy S Herbst 1, Megan A Baumgart 7, Jieling Miao 2, James Moon 2, Karen Kelly 8, David R Gandara 8

Affiliations

Clinical Trial

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

Sarah B Goldberg et al. J Clin Oncol. 2020.

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.

Trial registration: ClinicalTrials.gov NCT02438722.

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Conflict of interest statement

The author(s) meet criteria for authorship as recommended by the International Committee of Medical Journal Editors. Boehringer Ingelheim Pharmaceuticals (BIPI) had no role in the design, analysis or interpretation of the results in this study; BIPI was given the opportunity to review the manuscript for medical and scientific accuracy as it relates to BIPI substances, as well as intellectual property considerations. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Figures

FIG 1.

FIG 1.

CONSORT diagram. AE, adverse event; LFTs, liver function tests.

FIG 2.

FIG 2.

Progression-free survival (PFS). (A) Kaplan-Meier estimate of PFS. (B) Subgroup analysis of PFS. HR, hazard ratio.

FIG 3.

FIG 3.

Overall survival (OS). (A) Kaplan-Meier estimate of OS. (B) Subgroup analysis of OS. HR, hazard ratio.

FIG A1.

FIG A1.

Cumulative incidence of disease progression in the brain or other sites.

FIG A2.

FIG A2.

(A) Progression-free survival (PFS), and (B) overall survival (OS) of the different EGFR mutation subtypes. HR, hazard ratio.

FIG A3.

FIG A3.

(A) Progression-free survival (PFS), and (B) overall survival (OS) of afatinib + cetuximab versus afatinib alone in patients with EGFR exon 19 deletion mutations. HR, hazard ratio.

FIG A4.

FIG A4.

(A) Progression-free survival (PFS), and (B) overall survival (OS) of afatinib + cetuximab versus afatinib alone in patients with EGFR L858R mutations.

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