Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Clinical Pharmacology and Pharmacogenetics Unit, Department of Clinical and Experimental Medicine, University Hospital of Pisa, Pisa, Italy.
JCO Precis Oncol. 2022 Apr;6(1):e2200015. doi: 10.1200/PO.22.00015.
In GI cancers, anaplastic lymphoma kinase () 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.
We assembled a clinical and molecular international data set of pretreated patients with metastatic or nonresectable cancers of GI primary tumor origin with documented rearrangement treated with at least one line of ALKi. Measurable disease as per RECIST 1.1 was required for response analysis.
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).
Treatment with ALKi provides remarkable responses and clinical benefit in pretreated patients with ALK fusion-positive GI malignancies. Despite the rarity, 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.
在胃肠道癌症中，间变性淋巴瘤激酶（ALK）重排的频率远低于非小细胞肺癌，但在某些患者中，可能需要提供个性化的治疗策略。关于 ALK 抑制剂（ALKi）在胃肠道癌症中的活性和疗效的数据很少。
我们汇集了一组来自国际的、经预处理的、具有转移性或不可切除的胃肠道肿瘤的患者的临床和分子数据，这些患者的肿瘤起源于胃肠道，并且有明确的 重排，这些患者接受了至少一线的 ALKi 治疗。根据 RECIST 1.1 标准，需要可测量的疾病来进行反应分析。
原发肿瘤部位分布如下：5 例（38%）为胰腺，3 例（23%）为右结肠，1 例（8%）分别为胃、十二指肠、直肠、左半结肠和胆道。7 例（54%）患者接受阿来替尼治疗，5 例（38%）患者接受克唑替尼治疗，1 例（8%）患者接受恩曲替尼治疗。疾病进展后，5 例（38%）患者接受了二线 ALKi 治疗，截至数据截止日期，仍有 2 例患者在接受治疗。12 例可评估患者中，5 例（41%）患者对一线 ALKi 治疗有部分反应，5 例（41%）患者疾病稳定，2 例（17%）患者疾病进展。未观察到完全缓解。在中位随访 39.6 个月（四分位距：19.8-59.5）时，中位无进展生存期为 5.0 个月（95%CI：3.68 至无反应），中位总生存期为 9.3 个月（95%CI：5.46 至无反应）。
在预处理的 ALK 融合阳性胃肠道恶性肿瘤患者中，ALKi 治疗可提供显著的反应和临床获益。尽管罕见，但 重排代表了胃肠道实体肿瘤中个体患者的一个重要治疗靶点。需要进一步开展前瞻性临床验证该靶点的工作。
