Possibility of brigatinib-based therapy, or chemotherapy plus anti-angiogenic treatment after resistance of osimertinib harboring EGFR T790M-cis-C797S mutations in lung adenocarcinoma patients

There was no standard treatment for patients who acquired resistance to osimertinib mediated by epidermal growth factor receptor (EGFR) T790M-cis-C797S. The

Brigatinib-based therapy and chemotherapy plus anti-angiogenics could be considered beyond progression from osimertinib therapy. For patients harboring EGFR exon 19 deletion/T790M/cis-C797S mutation, the clinical efficacy was superior to patients harboring EGFR exon 21 p.L858R/T790M/cis-C797S mutation.

This retrospective cohort study analyzed 46 patients with metastatic lung adenocarcinoma and EGFR T790M-cis-C797S after osimertinib progression from January 1, 2017 to October 31, 2020. Among them, 13 patients received brigatinib-based therapy, 23 patients received chemotherapy in combination of anti-angiogenics or not, and 10 patients received other targeted treatments like dacomtinib, bevacizumab, or a combined therapy of osimertinib and other targeted drugs.

Compared to other targeted therapy, brigatinib-based therapy (median progression-free survival [mPFS]: 4.40 vs. 1.63 months, hazard ratio [HR] = 0.39, 95% confidence interval [CI]: 0.21-0.73, p = 0.001) and chemotherapy-based treatment (mPFS: 4.70 vs. 1.63 months, HR = 0.18, 95% CI: 0.06-0.50, p < 0.001) presented a better survival outcome and there was no significant difference between brigatinib-based therapy and chemotherapy-based treatment (mPFS: 4.40 vs. 4.70 months, HR = 1.24, 95% CI: 0.57-2.67, p = 0.58). Chemotherapy combined with anti-angiogenics achieved a better efficacy than only chemotherapy (mPFS: 5.50 vs. 1.03 months, HR = 0.30, 95% CI: 0.11-0.83, p = 0.02). Patients carrying EGFR exon 19 deletion mutation had a longer PFS than those who harboring EGFR exon 21 p.L858R mutation (4.57 vs. 1.03 months, HR = 0.18, 95% CI: 0.06-0.54, p = 0.001), no matter they received brigatinib-based therapy (mPFS: 5.00 vs. 3.23 months, HR = 0.19, 95% CI: 0.01-0.96, p = 0.05) or chemotherapy-based treatment (mPFS: 7.23 vs. 1.03 months, HR = 0.05, 95% CI 0.01-0.49, p < 0.001).