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

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.