Favorable survival outcomes in epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer sequentially treated with a tyrosine kinase inhibitor and osimertinib in a real-world setting

被引：3

作者：

Kraskowski, Oliver ^{[1
]}

Stratmann, Jan A. ^{[2
]}

Wiesweg, Marcel ^{[1
]}

Eberhardt, Wilfried ^{[1
]}

Metzenmacher, Martin ^{[1
]}

Schmid, Kurt W. ^{[3
,4
]}

Herold, Thomas ^{[3
]}

Schildhaus, Hans-Ulrich ^{[3
,4
]}

Darwiche, Kaid ^{[5
]}

Aigner, Clemens ^{[4
,6
]}

Stuschke, Martin ^{[4
,7
]}

Laue, Katharina ^{[1
]}

Zaun, Gregor ^{[1
]}

Kasper, Stefan ^{[1
,4
]}

Hense, Jorg ^{[1
]}

Sebastian, Martin ^{[2
,8
]}

Schuler, Martin ^{[1
,4
]}

Pogorzelski, Michael ^{[1
]}

机构：

[1] Univ Hosp Essen, West German Canc Ctr, Dept Med Oncol, Hufelandstr 55, D-46147 Essen, Germany

[2] Univ Hosp Frankfurt, Dept Internal Med, Hematol Oncol, Frankfurt, Germany

[3] Univ Hosp Essen, Inst Pathol, West German Canc Ctr, Essen, Germany

[4] Univ Hosp Essen, German Canc Consortium DKTK, Partner Site, Essen, Germany

[5] Univ Med Essen Ruhrlandklin, West German Canc Ctr, Dept Pneumol, Sect Intervent Pneumol, Essen, Germany

[6] Univ Med Essen Ruhrlandklin, West German Canc Ctr, Dept Thorac Surg & Surg Endoscopy, Essen, Germany

[7] Univ Duisburg Essen, Univ Hosp Essen, West German Canc Ctr, Dept Radiat Oncol, Essen, Germany

[8] Univ Hosp Frankfurt, German Canc Consortium DKTK, Partner Site, Frankfurt, Germany

来源：

JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY | 2023年 / 149卷 / 11期

关键词：

Sequential therapy; Osimertinib; Rebiopsy; EGFR-mutated NSCLC; EGFR T790M mutation; Second line; 1ST-LINE TREATMENT; OPEN-LABEL; EGFR-TKI; CHEMOTHERAPY; RESISTANCE; MUTATIONS; GEFITINIB; AFATINIB;

D O I：

10.1007/s00432-023-04839-3

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

PurposeEGFR tyrosine kinase inhibitor (TKI) therapy in EGFR-mutated lung cancer is limited by acquired resistance. In half of the patients treated with first/second-generation (1st/2nd gen) TKI, resistance is associated with EGFR p.T790M mutation. Sequential treatment with osimertinib is highly active in such patients. Currently, there is no approved targeted second-line option for patients receiving first-line osimertinib, which thus may not be the best choice for all patients. The present study aimed to evaluate the feasibility and efficacy of a sequential TKI treatment with 1st/2nd gen TKI, followed by osimertinib in a real-world setting.MethodsPatients with EGFR-mutated lung cancer treated at two major comprehensive cancer centers were retrospectively analyzed by the Kaplan-Meier method and log rank test.ResultsA cohort of 150 patients, of which 133 received first-line treatment with a first/second gen EGFR TKI, and 17 received first-line osimertinib, was included. Median age was 63.9 years, 55% had ECOG performance score of >= 1. First-line osimertinib was associated with prolonged progression-free survival (P = 0.038). Since the approval of osimertinib (February 2016), 91 patients were under treatment with a 1st/2nd gen TKI. Median overall survival (OS) of this cohort was 39.3 months. At data cutoff, 87% had progressed. Of those, 92% underwent new biomarker analyses, revealing EGFR p.T790M in 51%. Overall, 91% of progressing patients received second-line therapy, which was osimertinib in 46%. Median OS with sequenced osimertinib was 50 months. Median OS of patients with p.T790M-negative progression was 23.4 months.ConclusionReal-world survival outcomes of patients with EGFR-mutated lung cancer may be superior with a sequenced TKI strategy. Predictors of p.T790M-associated resistance are needed to personalize first-line treatment decisions.

引用

页码：9243 / 9252

页数：10

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