奥希替尼耐药的肺腺癌患者存在 EGFR T790M-cis-C797S 突变时，采用布加替尼为基础的治疗，或化疗联合抗血管生成治疗的可能性。
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.
机构信息
Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Comprehensive Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
出版信息
Cancer Med. 2021 Dec;10(23):8328-8337. doi: 10.1002/cam4.4336. Epub 2021 Oct 6.
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.
背景
对于奥希替尼介导的表皮生长因子受体（EGFR）T790M-cis-C797S 耐药的患者，目前尚无标准治疗方法。本研究旨在探讨这些患者不同治疗策略与生存结局之间的关系。
方法
本回顾性队列研究分析了 2017 年 1 月 1 日至 2020 年 10 月 31 日期间 46 例接受奥希替尼治疗后进展的转移性肺腺癌和 EGFR T790M-cis-C797S 患者。其中，13 例患者接受布加替尼为基础的治疗，23 例患者接受化疗联合或不联合抗血管生成治疗，10 例患者接受其他靶向治疗，如达克替尼、贝伐珠单抗或奥希替尼联合其他靶向药物的联合治疗。
结果
与其他靶向治疗相比，布加替尼为基础的治疗（中位无进展生存期[mPFS]：4.40 个月比 1.63 个月，风险比[HR]为 0.39，95%置信区间[CI]为 0.21-0.73，p=0.001）和化疗为基础的治疗（mPFS：4.70 个月比 1.63 个月，HR 为 0.18，95%CI 为 0.06-0.50，p<0.001）的生存结局更好，且布加替尼为基础的治疗与化疗为基础的治疗之间无显著差异（mPFS：4.40 个月比 4.70 个月，HR 为 1.24，95%CI 为 0.57-2.67，p=0.58）。化疗联合抗血管生成治疗比单纯化疗的疗效更好（mPFS：5.50 个月比 1.03 个月，HR 为 0.30，95%CI 为 0.11-0.83，p=0.02）。携带 EGFR 外显子 19 缺失突变的患者比携带 EGFR 外显子 21 p.L858R 突变的患者具有更长的 PFS（4.57 个月比 1.03 个月，HR 为 0.18，95%CI 为 0.06-0.54，p=0.001），无论他们接受布加替尼为基础的治疗（mPFS：5.00 个月比 3.23 个月，HR 为 0.19，95%CI 为 0.01-0.96，p=0.05）还是化疗为基础的治疗（mPFS：7.23 个月比 1.03 个月，HR 为 0.05，95%CI 为 0.01-0.49，p<0.001）。
结论
布加替尼为基础的治疗和化疗联合抗血管生成治疗可能是奥希替尼治疗进展后的治疗选择。对于携带 EGFR 外显子 19 缺失/T790M/cis-C797S 突变的患者，临床疗效优于携带 EGFR 外显子 21 p.L858R/T790M/cis-C797S 突变的患者。
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