Hu Yan, Ren Siying, Wang Ruoyao, Han Wei, Xiao Peng, Wang Li, Yu Fenglei, Liu Wenliang
Department of Thoracic Surgery, The Second Xiangya Hospital of Central South University, Hunan Key Laboratory of Early Diagnosis and Precision Treatment of Lung Cancer, The Second Xiangya Hospital of Central South University, Changsha, China.
Department of Respiratory and Critical Care Medicine, The Second Xiangya Hospital of Central South University, Research Unit of Respiratory Disease, Central South University, Hunan Diagnosis and Treatment Center of Respiratory Disease, Changsha, China.
Front Pharmacol. 2022 Jul 6;13:816683. doi: 10.3389/fphar.2022.816683. eCollection 2022.
Alectinib, a highly selective inhibitor of ALK, is currently used in the first-line setting of untreated advanced ALK-positive NSCLC and in the second-line setting of crizotinib-resistant ALK-positive NSCLC. Despite promising efficacy and tolerability in the treatment of advanced ALK-positive NSCLC, the activity of alectinib as neoadjuvant therapy in resectable ALK-positive NSCLC remains to be investigated. Herein, we report a case of a 58-year-old female patient presented to our hospital with hemoptysis for 1 month. Contrast-enhanced computerized tomography (CT) of the chest showed an approximately 4.2 × 3.4 cm mass in the right hilum with localized obstructive pneumonia in the right lower lobe and multiple enlarged lymph nodes in the right hilum and mediastinum. Serum oncological markers results showed elevated levels of CA19-9, CEA, CA125, and CA242. Bronchoscopic biopsy of the mass showed poorly differentiated pulmonary adenocarcinoma and immunohistochemical testing results confirmed ALK positivity. Neoadjuvant alectinib was given at a dosage of 600 mg twice per day for two cycles (56 days), achieving a partial response of the disease with 90% shrinkage of the mass at the subsequent whole-body positron emission tomography. Repeat serum oncological markers results showed that only CA125 was elevated, but lower than before therapy. A bilobectomy of the right middle and lower lobes and systemic lymphadectomy under video-assisted thoracoscopic approach was successfully performed 7 days after the last dose of alectinib. Postoperative pathology showed pathological complete response (pCR). The patient experienced an uneventful postoperative course and continued to receive alectinib and did not report any specific discomfort at her 8-month follow-up. Thoracoabdominal CT at 8 months postoperatively showed no recurrence and repeated examination of serum oncological markers were negative. We report a case of resectable ALK-positive NSCLC treated with neoadjuvant aletinib achieving pCR. Our case highlights the feasibility of alectinib as neoadjuvant therapy for the treatment of resectable ALK-positive NSCLC. Undoubtedly, the safety and efficacy of this novel treatment modality needs to be explored in future large clinical trials.
阿来替尼是一种高度选择性的ALK抑制剂，目前用于未经治疗的晚期ALK阳性非小细胞肺癌（NSCLC）的一线治疗以及克唑替尼耐药的ALK阳性NSCLC的二线治疗。尽管阿来替尼在治疗晚期ALK阳性NSCLC方面具有令人鼓舞的疗效和耐受性，但其作为可切除的ALK阳性NSCLC新辅助治疗的活性仍有待研究。在此，我们报告一例58岁女性患者，因咯血1个月就诊于我院。胸部增强计算机断层扫描（CT）显示右肺门有一个约4.2×3.4 cm的肿块，右下叶有局限性阻塞性肺炎，右肺门和纵隔有多个肿大淋巴结。血清肿瘤标志物结果显示CA19-9、癌胚抗原（CEA）、CA125和CA242水平升高。肿块的支气管镜活检显示为低分化肺腺癌，免疫组化检测结果证实ALK阳性。给予阿来替尼新辅助治疗，剂量为600 mg，每日两次，共两个周期（56天），在随后的全身正电子发射断层扫描中疾病获得部分缓解，肿块缩小90%。重复血清肿瘤标志物结果显示只有CA125升高，但低于治疗前。在最后一剂阿来替尼7天后，成功通过电视辅助胸腔镜手术进行了右中、下叶双叶切除术和系统性淋巴结清扫术。术后病理显示病理完全缓解（pCR）。患者术后恢复顺利，继续接受阿来替尼治疗，在8个月的随访中未报告任何特殊不适。术后8个月的胸腹部CT显示无复发，血清肿瘤标志物复查为阴性。我们报告一例接受阿来替尼新辅助治疗达到pCR的可切除ALK阳性NSCLC病例。我们的病例突出了阿来替尼作为可切除ALK阳性NSCLC新辅助治疗的可行性。毫无疑问，这种新型治疗方式的安全性和有效性需要在未来的大型临床试验中进行探索。
