Open AccessPossibility of brigatinib‐based therapy, or chemotherapy plus anti‐angiogenic treatment after resistance of osimertinib harboring EGFR T790M‐ cis ‐C797S mutations in lung adenocarcinoma patients
Author(s) -
Yang Yaning,
Xu Haiyan,
Ma Li,
Yang Lu,
Yang Guangjian,
Zhang Shuyang,
Ai Xin,
Zhang Shucai,
Wang Yan
Publication year - 2021
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.4336
Subject(s) - osimertinib , medicine , t790m , bevacizumab , lung cancer , chemotherapy , oncology , hazard ratio , adenocarcinoma , combination therapy , epidermal growth factor receptor , gastroenterology , confidence interval , cancer , gefitinib , ros1
Abstract Background There was no standard treatment for patients who acquired resistance to osimertinib mediated by epidermal growth factor receptor ( EGFR ) T790M‐ cis ‐C797S. The aim of this study was to investigate the association between different therapeutic strategies and survival outcomes among these patients. Methods 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. Results 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). Conclusion 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.