ALK Inhibitors in Patients With ALK Fusion-Positive GI Cancers: An International Data Set and a Molecular Case Series

被引：20

作者：

Ambrosini, Margherita ^{[1
]}

Del Re, Marzia ^{[2
]}

Manca, Paolo ^{[1
]}

Hendifar, Andrew ^{[3
]}

Drilon, Alexander ^{[4
]}

Harada, Guilherme ^{[4
]}

Ree, Anne Hansen ^{[5
,6
]}

Klempner, Samuel ^{[7
]}

Maelandsmo, Gunhild Mari ^{[8
]}

Flatmark, Kjersti ^{[9
]}

Russnes, Hege G. ^{[10
,11
]}

Cleary, James M. ^{[12
]}

Singh, Harshabad ^{[12
]}

Sottotetti, Elisa ^{[1
]}

Martinetti, Antonia ^{[1
]}

Randon, Giovanni ^{[1
]}

Sartore-Bianchi, Andrea ^{[13
]}

Capone, Iolanda ^{[14
]}

Milione, Massimo ^{[14
]}

Di Bartolomeo, Maria ^{[1
]}

Pietrantonio, Filippo ^{[1
]}

机构：

[1] Fdn IRCCS Ist Nazl Tumori, Dept Med Oncol, Milan, Italy

[2] Univ Hosp Pisa, Dept Clin & Expt Med, Clin Pharmacol & Pharmacogenet Unit, Pisa, Italy

[3] Cedars Sinai Med Ctr, Div Hematol & Oncol, Los Angeles, CA 90048 USA

[4] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA

[5] Akershus Univ Hosp, Dept Oncol, Lorenskog, Norway

[6] Univ Oslo, Inst Clin Med, Oslo, Norway

[7] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA

[8] Norwegian Radium Hosp, Oslo Univ Hosp, Inst Canc Res, Dept Tumor Biol, Oslo, Norway

[9] Oslo Univ Hosp, Norwegian Radium Hosp, Dept Surg Gastroenterol, Oslo, Norway

[10] Oslo Univ Hosp, Dept Pathol, Div Lab Med, Oslo, Norway

[11] Oslo Univ Hosp, Inst Canc Res, Div Canc Med, Oslo, Norway

[12] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[13] Univ Milano La Statale, Dept Oncol & Hematooncol, Milan, Italy

[14] Fdn IRCCS Ist Nazl Tumori, Dept Pathol, Milan, Italy

来源：

JCO PRECISION ONCOLOGY | 2022年 / 6卷 / 01期

关键词：

COLORECTAL-CANCER; SOLID TUMORS; RECEPTOR; KINASE; LAROTRECTINIB; ENTRECTINIB;

D O I：

10.1200/PO.22.00015

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

PURPOSE In GI cancers, anaplastic lymphoma kinase (ALK) rearrangements are extremely less frequent than in non-small-cell lung cancer but may be important to offer personalized strategies of treatment in selected patients. Data about the activity and efficacy of ALK inhibitors (ALKi) in GI cancers are scarce. MATERIALS AND METHODS We assembled a clinical and molecular international data set of pretreated patients with metastatic or nonresectable cancers of GI primary tumor origin with documented ALK rearrangement treated with at least one line of ALKi. Measurable disease as per RECIST 1.1 was required for response analysis. RESULTS Primary tumor sites were distributed as follows: 5 (38%) pancreas, 3 (23%) right colon, and 1 (8%) for each one of gastric, duodenal, rectal, left colon, and biliary tract sites. Seven patients (54%) were treated with alectinib, 5 (38%) with crizotinib, and 1 (8%) with entrectinib. After disease progression, five patients (38%) received a subsequent ALKi treatment line, and at the time of data cutoff date, treatment was still ongoing in two patients. Five of 12 evaluable patients (41%) achieved a partial response to first-line ALKi, five patients (41%) had stable disease, and 2 (17%) had progressive disease. No complete responses were registered. At a median follow-up of 39.6 months (interquartile range: 19.8-59.5), the median progression-free survival was 5.0 months (95% CI, 3.68 to no response) and the median overall survival was 9.3 months (95% CI, 5.46 to no response). CONCLUSION Treatment with ALKi provides remarkable responses and clinical benefit in pretreated patients with ALK fusion-positive GI malignancies. Despite the rarity, ALK rearrangements represent an important therapeutic target in individual pretreated patients with GI solid tumors. Further work providing prospective clinical validation of this target is needed. (C) 2022 by American Society of Clinical Oncology

引用

页数：10

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