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Background  Co-mutations was associated with poor response to EGFR-TKIs. First-generation EGFR-TKIs combined with chemotherapy was reported to be more effective than TKIs alone in advanced lung adenocarcinoma patients.    Objective  This retrospective study aimed to explore whether  EGFR -mutant patients with co-mutations can benefit from EGFR-TKIs plus chemotherapy.    Patients and Methods  We retrospectively collected data of 137  EGFR -mutant patients with advanced lung adenocarcinoma who underwent next-generation sequencing in our hospital in 2018. Among them, 96 were treated with EGFR–TKIs alone and 41 received EGFR–TKIs plus chemotherapy. We analyzed the progression-free survival (PFS) of patients with co-mutations using different treatments.    Results  Concurrent  TP53  mutations, especially exon 4 and 6, were associated with a markedly shorter time to progression on EGFR-TKI monotherapy (11.4 months  vs . 16.6 months,  P =0.003), while EGFR–TKIs plus chemotherapy would benefit those patients more (with  TP53:  11.4 months  vs . 19.1 months,  P =0.001, HR=0.407; without  TP53 : 16.6 months  vs . 18.9 months,  P =0.379, HR=0.706). The incidence of T790M after resistance was equal in patients treated with different treatments (53%  vs . 53%,  P =0.985).    Conclusions  In our study, concurrent  TP53  mutations were found to be risk factors for EGFR-TKI monotherapy, but TKI combined with chemotherapy could eliminate this heterogeneity.

Efficacy of EGFR-TKI Plus Chemotherapy or Monotherapy as First-Line Treatment for Advanced EGFR-Mutant Lung Adenocarcinoma Patients With Co-Mutations