Efficacy and Tolerability of ALK/MET Combinations in Patients With ALK-Rearranged Lung Cancer With Acquired MET Amplification: A Retrospective Analysis.
Efficacy and Tolerability of ALK/MET Combinations in Patients With ALK-Rearranged Lung Cancer With Acquired MET Amplification: A Retrospective Analysis.
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DOI：
10.1016/j.jtocrr.2023.100534
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发表时间：
2023-08
影响因子：
--
通讯作者：
Digumarthy, Subba R.
中科院分区：
文献类型：
--
作者：
Dagogo-Jack, Ibiayi;Kiedrowski, Lesli A.;Heist, Rebecca S.;Lin, Jessica J.;Meador, Catherine B.;Krueger, Elizabeth A.;Do, Andrew;Peterson, Jennifer;V. Sequist, Lecia;Gainor, Justin F.;Lennerz, Jochen K.;Digumarthy, Subba R.
MET扩增是ALK重排（ALK+）肺癌的潜在可操作耐药机制。缺乏描述该分子亚组治疗结果的研究。我们组建了一个ALK+肺癌患者队列，这些患者接受了靶向ALK和MET的方案，并获得了MET扩增（通过组织或血浆识别）。分别使用实体瘤疗效评价标准版本1.1和不良事件通用术语标准版本4.03评估疗效和安全性。共有12名患者被纳入该系列。在中位数1.5（范围1-5）线治疗后检测到MET扩增。实施了四种不同的方案来解决MET扩增：克唑替尼（n = 2）、劳拉替尼+克唑替尼（n = 6）、阿来替尼+卡匹替尼（n = 3）和阿来替尼+克唑替尼（n = 1）。在12例患者中的5例（42%）中观察到部分缓解，包括接受克唑替尼（n = 12）、劳拉替尼+克唑替尼（n = 3/6）和alectinib + capmatinib（n = 1/3）的患者。在4例患者（33%）中观察到原发性进展。克唑替尼和capmatinib均发现7例（58%）患者发生1 - 2级外周水肿。1例患者因持续性2级水肿需要降低capmatinib + alectinib的剂量。在所有治疗方案中，1例患者因毒性而停止治疗，特别是劳拉替尼联合克唑替尼的神经认知毒性。ALK+ MET治疗进展时，潜在耐药机制包括MET拷贝数变化和ALK激酶结构域突变。在伴有MET扩增的ALK+ NSCLC患者中，ALK和MET联合抑制与中度抗肿瘤活性相关。前瞻性研究旨在确认活性并确定最有可能从治疗中获益的个体。
MET amplification is a potentially actionable resistance mechanism in ALK-rearranged (ALK+) lung cancer. Studies describing treatment outcomes of this molecular subgroup are lacking. We assembled a cohort of patients with ALK+ lung cancer and acquired MET amplification (identified by tissue or plasma) who received regimens targeting both ALK and MET. Efficacy and safety were assessed using the Response Evaluation Criteria in Solid Tumors version 1.1 and Common Terminology Criteria for Adverse Events version 4.03, respectively. A total of 12 patients were included in the series. MET amplification was detected after a median of 1.5 (range 1–5) lines of therapy. Four distinct regimens were implemented to address MET amplification: crizotinib (n = 2), lorlatinib plus crizotinib (n = 6), alectinib plus capmatinib (n = 3), and alectinib plus crizotinib (n = 1). Partial responses were observed in five (42%) of 12 patients, including patients who received crizotinib (n = one of two), lorlatinib plus crizotinib (n = three of six), and alectinib plus capmatinib (n = one of three). Primary progression was observed in four patients (33%). Grades 1 to 2 peripheral edema, occurring in seven (58%) patients, was found with both crizotinib and capmatinib. One patient required dose reduction of capmatinib plus alectinib for persistent grade 2 edema. Across the regimens, one patient discontinued therapy for toxicity, specifically neurocognitive toxicity from lorlatinib plus crizotinib. At progression on ALK+ MET therapy, potential resistance mechanisms included MET copy number changes and ALK kinase domain mutations. Combined ALK and MET inhibition is associated with moderate antitumor activity in patients with ALK+ NSCLC with concurrent MET amplification. Prospective studies are indicated to confirm activity and identify individuals most likely to benefit from the treatment.
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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：
28.2
作者：
Lin JJ;Riely GJ;Shaw AT
通讯作者：
Shaw AT
影响因子：
46.9
作者：
Frampton GM;Fichtenholtz A;Otto GA;Wang K;Downing SR;He J;Schnall-Levin M;White J;Sanford EM;An P;Sun J;Juhn F;Brennan K;Iwanik K;Maillet A;Buell J;White E;Zhao M;Balasubramanian S;Terzic S;Richards T;Banning V;Garcia L;Mahoney K;Zwirko Z;Donahue A;Beltran H;Mosquera JM;Rubin MA;Dogan S;Hedvat CV;Berger MF;Pusztai L;Lechner M;Boshoff C;Jarosz M;Vietz C;Parker A;Miller VA;Ross JS;Curran J;Cronin MT;Stephens PJ;Lipson D;Yelensky R
通讯作者：
Yelensky R
影响因子：
20.4
作者：
Vokes, Natalie, I;Chambers, Emily;Nguyen, Tom;Coolidge, Alexis;Lydon, Christine A.;Le, Xiuning;Sholl, Lynette;Heymach, John, V;Nishino, Mizuki;Van Allen, Eliezer M.;Janne, Pasi A.
通讯作者：
Janne, Pasi A.
影响因子：
28.2
作者：
Gainor JF;Dardaei L;Yoda S;Friboulet L;Leshchiner I;Katayama R;Dagogo-Jack I;Gadgeel S;Schultz K;Singh M;Chin E;Parks M;Lee D;DiCecca RH;Lockerman E;Huynh T;Logan J;Ritterhouse LL;Le LP;Muniappan A;Digumarthy S;Channick C;Keyes C;Getz G;Dias-Santagata D;Heist RS;Lennerz J;Sequist LV;Benes CH;Iafrate AJ;Mino-Kenudson M;Engelman JA;Shaw AT
通讯作者：
Shaw AT