Data from a pooled analysis supported the use of afatinib in the treatment of patients with non-small cell lung cancer (NSCLC) harboring uncommon EGFR mutations.

The study included data on 693 patients with T790M, exon 20 insertions, major uncommon mutations (G719X, L861Q and S768I), compound mutations, and other uncommon mutations. Patients were from randomized clinical trials, compassionate-use and expanded-access programs, non-interventional trials, and case series.

Among patients naive to afatinib, the median time to treatment failure was 10.8 months for patients with major uncommon mutations, 14.7 months for those with compound mutations, 4.5 months for those with other uncommon mutations, and 4.2 months among patients with exon 20 insertions.

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Similarly, the median duration of response was longest among those patients with major uncommon mutations (17.1 months) compared with compound mutations (16.6 months), exon 20 insertions (11.9 months), and other uncommon mutations (9.0 months).

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Among those patients with prior afatinib exposure, median time to treatment failure was highest among those patients with compound mutations (5.8 months), especially those with major uncommon mutation (9.3 months).

“The widespread implementation of NGS in routine clinical practice, together with improvements in the sensitivity of NGS assays and their transfer into the liquid biopsy setting, are likely to improve the detection of EGFR mutations in the future, including uncommon mutations,” the researchers wrote. “Accordingly, the data herein will provide important information when considering optimal treatment for NSCLC patients harboring specific uncommon EGFR mutations, including compound mutations.”


Yang JCH, Schuler M, Popat S, et al. Afatinib for the treatment of non-small cell lung cancer harboring uncommon EGFR mutations: a database of 693 cases [published January 10, 2020]. J Thorac Oncol. doi: 10.1016/j.jtho.2019.12.126