Efficacy and Safety of Chemotherapy or EGFR-TKIs as First-Line Therapy in NSCLC Patients Harboring Non-Ex 20 Ins Uncommon EGFR Mutations: A Retrospective Study in China

BackgroundUncommon EGFR mutations are a kind of heterogeneous group of mutations with various responses to EGFR-TKIs and are often excluded from most prospective clinical trials. In this real-world retrospective study, we retrospectively compared the efficacy and safety of chemotherapy or various generations of EGFR-TKIs as first-line therapy in NSCLC Chinese patients harboring non-ex 20 ins uncommon EGFR mutations.MethodsWe enrolled 139 NSCLC patients with non-ex 20 ins uncommon EGFR mutations in this study retrospectively. Patients' clinical characteristics and the efficacy and safety of different first-line therapies were analyzed and compared.ResultsOur data reviewed that for first-line therapy, NSCLC patients harboring non-ex 20 ins uncommon EGFR mutations benefited more from EGFR-TKIs compared with chemotherapy. Afatinib performed with great efficacy for the majority of non-ex 20 ins uncommon EGFR mutations (N = 43, ORR = 41.86%, mPFS = 13.5 months, mOS = 20.8 months), especially in L861Q mutation (mPFS = 18.4 months). Osimertinib also demonstrated efficacy in patients harboring non-ex 20 ins uncommon EGFR mutations (N = 36, ORR = 27.78%, mPFS = 10.0 months, mOS = 21.0 months), especially in those without L861Q and G719X mutations (mPFS = 12.1 months). When treated with afatinib, patients harboring non-ex 20 ins uncommon EGFR mutations should pay attention to the management of safety, especially for gastrointestinal-related AE and rash, while osimertinib was safer.ConclusionTaking into account both efficacy and safety, afatinib and osimertinib are better choices than chemotherapy and first-generation EGFR-TKIs for NSCLC patients with non-ex 20 ins uncommon EGFR mutations. L861Q showed a trend toward a better response to afatinib, while in those without L861Q and G719X mutations, osimertinib might be a better choice. Safety also should be a concern when choosing EGFR-TKI for treatment, patients should pay attention to the management of safety when using afatinib while osimertinib is safer.