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ERBB Mutations and Outcomes With Afatinib and Erlotinib in Squamous NSCLC

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Key Points

  • Outcomes were better with afatinib in patients with vs without ERBB mutations.
  • The presence of HER2 mutations was associated with improved outcome with afatinib vs erlotinib.  

In an analysis of the LUX-Lung 8 trial in squamous non–small cell lung cancer (NSCLC) reported in JAMA Oncology, Goss et al found that outcomes among patients treated with afatinib (Gilotrif) were better for those with vs without ERBB mutations.

The LUX-Lung 8 trial showed that afatinib was associated with superior overall and progression-free survival vs erlotinib (Tarceva) in a total of 795 patients with stage IIIB or IV squamous NSCLC with progressive disease after 4 or more cycles of platinum-based chemotherapy.

Study Details

The current analysis involved 245 patients—132 treated with afatinib and 113 with erlotinib—with tumor specimens eligible for tumor genetic analysis (TGA) with next-generation sequencing. The TGA cohort was enriched for patients with progression-free survival > 2 months.

Outcomes in the ERBB Mutation Subgroup

In the TGA cohort, median progression-free survival (3.5 vs 2.5 months, hazard ratio [HR] = 0.69, P = .01) and overall survival (8.4 vs 6.6 months, HR = 0.81, P = .12) were better among patients treated with afatinib. Of 245 patients in the TGA subset, 53 (21.6%) had tumors with 1 or more ERBB mutations.

Among afatinib-treated patients, median progression-free survival (4.9 vs 3.0 months, HR = 0.62, P = .06) and overall survival (10.6 vs 8.1 months, HR = 0.75, P = .21) were nonsignificantly longer among those with vs without ERBB mutations. Among erlotinib-treated patients, differences in median progression-free survival (2.7 vs 2.4 months, HR = 0.76, P = .29) and overall survival (7.2 vs 6.4 months, HR = 0.84, P = .46) between those with vs without ERBB mutations were smaller compared with afatinib-treated patients.

Among 12 patients with HER2 mutations, afatinib vs erlotinib treatment was associated with better progression-free survival (HR = 0.06, 95% confidence interval [CI] =0.01–0.59) and overall survival (HR = 0.06, 95% CI = 0.01–0.57). Among patients without HER2 mutations, hazard ratios were 0.69 (95% CI = 0.51–0.94) and 0.83 (95% CI = 0.64–1.09) for progression-free and overall survival. No apparent association was found between copy number alteration or EGFR expression level and outcomes.

The investigators concluded, “Next-generation sequencing may help identify patients with lung squamous cell carcinoma who would derive additional benefit from treatment with afatinib. The role of ERBB mutations, particularly HER2 mutations, as predictive biomarkers for afatinib treatment in this setting warrants further evaluation.”

This study was funded by Boehringer Ingelheim.

Glenwood D. Goss, MD, The Ottawa Hospital Research Institute, University of Ottawa, is the corresponding author for the JAMA Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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