Brief Report: Effective treatment of lung adenocarcinoma harboring EGFR-activating mutation/T790M/cis-C797S triple mutations by brigatinib and cetuximab combination therapy

Abstract Background Acquired resistance to osimertinib mediated by EGFR cis-C797S is now a growing challenge. No effective treatment strategy is currently available to overcome cis-C797S-mediated resistance. Methods In this retrospective cohort study, 15 patients with advanced lung adenocarcinoma were identified with EGFR-activating mutation/T790M/cis-C797S after osimertinib progression by targeted next-generation sequencing. Five patients received combined therapy of brigatinib and cetuximab, and ten patients received cisplatin-based doublet chemotherapy. Results Among the five EGFR 19del/T790M/cis-C797S-positive patients who received brigatinib and cetuximab combination therapy, three patients achieved partial response (PR) and two had stable disease (SD), resulting in an objective response rate (ORR) of 60% and disease control rate (DCR) of 100%. Meanwhile, among the ten EGFR 19del or L858R/T790M/cis-C797S-positive patients who received chemotherapy, only one patient achieved PR, five had SD, and four did not benefit from chemotherapy, resulting in ORR and DCR of 10% and 60%, respectively. The median progression-free survival (PFS) of patients who received combined targeted therapy was 14 months, and 3 months for those treated with chemotherapy. No grade III-IV adverse events were observed in all the patients. Conclusion Our retrospective study provides clinical evidence that combined targeted therapy of brigatinib and cetuximab could provide benefit and may potentially be an effective treatment strategy to improve survival outcomes of patients who acquired EGFR T790M/cis-C797S-mediated resistance to osimertinib.