An ALK-positive NSCLC patient with the G1202R mutation detected by next-generation sequencing

作者：Yoshimura Katsuhiro; Imokawa Shiro; Inoue Yusuke; Ohnishi Ippei; Kahyo Tomoaki; Suzuki Shioto; Ueno Toshihide; Tanioka Fumihiko; Soda Manabu; Suda Takafumi; Mano Hiroyuki; Sugimura Haruhiko^*

来源：International Journal of Clinical and Experimental Pathology, 2016, 9(6): 6568-6573.

• ALK G1202R
• alectinib
• resistance
• ALK-positive NSCLC
• next-generation sequencing

Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors are currently essential drugs in the treatment of the subset of patients with non-small-cell lung cancer (NSCLC) showing ALK rearrangement. Notwithstanding, even the response to ALK inhibitors is usually not sustained in these patients, because of the occurrence of secondary mutations in ALK, MET amplification, or other unknown alterations. Herein, we report the case of a 70-year-old Japanese woman who was diagnosed as having advanced adenocarcinoma of the lung with ALK rearrangement. Treatment with crizotinib as well as with pemetrexed yielded good responses initially, however, the disease eventually progressed. Then, treatment with alectinib, a second-generation ALK inhibitor, was initiated, which yielded a dramatic response, which was sustained approximately for two months. When the disease progressed again, we re-challenged the patient with pemetrexed again, which resulted in marked tumor shrinkage, however, the tumor eventually recurred again. At autopsy, tumors were found in the lung, hilar lymph nodes, spleen, pleura and peritoneum, and examination of the lung tumor tissue obtained at autopsy by next-generation sequencing (NGS) revealed G1202R substitution, a secondary ALK mutation. Our experience emphasizes the importance of repeated genomic analyses of the tumor tissue at several time-points during the course of time, including after death, to explain intractable cancer progression under molecular-targeted therapy. An important lesson from this case is that the timing of treatment with regimens including molecular-target agents and other conventional therapies must be chosen taking into account the underlying molecular events in the tumors.

• 出版日期2016