Case report: Success of tepotinib therapy in overcoming resistance to osimertinib in a patient with EGFR-mutant lung adenocarcinoma with a potential acquired MET exon 14 skipping mutation.
Case report: Success of tepotinib therapy in overcoming resistance to osimertinib in a patient with EGFR-mutant lung adenocarcinoma with a potential acquired MET exon 14 skipping mutation.
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DOI：
10.3389/fonc.2022.965741
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发表时间：
2022
影响因子：
4.7
通讯作者：
Okamoto, Tatsuro
中科院分区：
文献类型：
--
作者：
Takamori, Shinkichi;Seto, Takashi;Yamaguchi, Masafumi;Kinoshita, Fumihiko;Fujishita, Takatoshi;Ito, Kensaku;Toyozawa, Ryo;Shoji, Fumihiro;Okamoto, Tatsuro
奥希替尼是治疗携带表皮生长因子受体基因（EGFR）突变的晚期非小细胞肺癌（NSCLC）的标准疗法，但大多数EGFR突变型NSCLC患者对奥希替尼发生继发性耐药。间质-上皮转化基因（MET）改变和癌基因融合已被确定为奥希替尼耐药的最常见机制。然而，MET外显子14跳跃突变（METex 14 del）作为对奥希替尼的获得性耐药的报道很少。一名不吸烟的76岁女性被诊断出患有右下叶肺腺癌（cT 2bN 2 M1 c [肺和骨转移]，cStage IVB）。将原发性肿瘤进行cobas® EGFR突变测试v2（Roche Diagnostics Ltd.），下一代测序（Oncomine Comprehensive Assay v3; Thermo Fisher Scientific）、AmoyDx® Essential NGS panel（Amoy Diagnostics，Xiamen，China），所有这些均为EGFR L 858 R和从头T790 M阳性。我们每天给予奥希替尼（80 mg/天），并获得部分缓解。然而，14.0个月后，计算机断层扫描显示原发性肿瘤和肺转移的进展。对原发性肿瘤进行再次活检，并将标本提交给Archer®MET伴随诊断以检测METex 14 del。尽管原发肿瘤对METex 14 del呈阴性，但再次活检标本对METex 14 del呈阳性。我们使用局部逆转录PCR验证了奥希替尼给药前诊断时原发性肿瘤的活检标本对METex 14 del呈阴性。我们每日给予患者tepotinib（500 mg/天）作为进一步治疗，并在2.0个月后达到部分缓解（肿瘤缩小率：34.5%），该患者对tepotinib治疗有反应8.0个月。我们描述了一例携带METex 14 del的肺腺癌患者，该患者对奥希替尼具有潜在的获得性耐药，对后续tepotinib治疗有反应。在发生奥希替尼耐药的NSCLC患者中，应考虑重新活检和重新分析遗传特征。
Osimertinib is a standard therapy for the treatment of advanced non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor gene (EGFR) mutations, but most patients with EGFR-mutant NSCLC develop secondary resistance to osimertinib. Mesenchymal-epithelial transition gene (MET) alterations and oncogene fusions have been identified as the most common mechanisms of resistance to osimertinib. However, MET exon 14 skipping mutation (METex14del) as an acquired resistance to osimertinib has rarely been reported. A non-smoking 76-year-old woman was diagnosed with lung adenocarcinoma in the right lower lobe (cT2bN2M1c [pulmonary and bone metastases], cStage IVB). The primary tumor was submitted to cobas® EGFR Mutation Test v2 (Roche Diagnostics Ltd.), next generation sequencing (Oncomine Comprehensive Assay v3; Thermo Fisher Scientific), the AmoyDx® Essential NGS panel (Amoy Diagnostics, Xiamen, China), all of which were positive for EGFR L858R and de novo T790M. We administered daily osimertinib (80 mg/day), and achieved a partial response. However, after 14.0 months, computed tomography showed progression of the primary tumor and lung metastases. Re-biopsy of the primary tumor was conducted, and the specimen was submitted to Archer®MET companion diagnostic for detection of METex14del. Although the primary tumor was negative for METex14del, the re-biopsy specimen was positive for METex14del. We validated that the biopsy specimen of the primary tumor at diagnosis before osimertinib administration was negative for METex14del using local reverse transcription PCR. We administered daily tepotinib (500 mg/day) to the patient as a further-line treatment, and achieved a partial response (tumor shrinkage rate: 34.5%) after 2.0 months, who responded to tepotinib therapy for 8.0 months. We described a patient with lung adenocarcinoma harboring METex14del as a potential acquired resistance to osimertinib, who responded to subsequent tepotinib therapy. Re-biopsy and re-analysis of genetic profiles should be considered in NSCLC patients who develop osimertinib resistance.
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DOI：
10.1056/nejmoa2004407
发表时间：
2020-09-03
期刊：
The New England journal of medicine
影响因子：
--
作者：
Paik PK;Felip E;Veillon R;Sakai H;Cortot AB;Garassino MC;Mazieres J;Viteri S;Senellart H;Van Meerbeeck J;Raskin J;Reinmuth N;Conte P;Kowalski D;Cho BC;Patel JD;Horn L;Griesinger F;Han JY;Kim YC;Chang GC;Tsai CL;Yang JC;Chen YM;Smit EF;van der Wekken AJ;Kato T;Juraeva D;Stroh C;Bruns R;Straub J;Johne A;Scheele J;Heymach JV;Le X
通讯作者：
Le X
影响因子：
51.1
作者：
Sequist, Lecia, V;Han, Ji-Youn;Oxnard, Geoffrey
通讯作者：
Oxnard, Geoffrey
影响因子：
158.5
作者：
Soria, J. -C.;Ohe, Y.;Nguyen, Nhung
通讯作者：
Nguyen, Nhung
影响因子：
3.6
作者：
Pinquie, Francois;Cortot, Alexis B.;Molinier, Olivier
通讯作者：
Molinier, Olivier
DOI：
10.1056/nejmoa1612674
发表时间：
2017-02-16
期刊：
The New England journal of medicine
影响因子：
--
作者：
Mok TS;Wu Y-L;Ahn M-J;Garassino MC;Kim HR;Ramalingam SS;Shepherd FA;He Y;Akamatsu H;Theelen WS;Lee CK;Sebastian M;Templeton A;Mann H;Marotti M;Ghiorghiu S;Papadimitrakopoulou VA;AURA3 Investigators
通讯作者：
AURA3 Investigators