Zheng Zhe-Rong, Ku Hsiu-Ying, Chen Kun-Chieh, Chiang Chun-Ju, Wang Chih-Liang, Chen Chih-Yi, Tsai Chun-Ming, Huang Ming-Shyan, Yu Chong-Jen, Chen Jin-Shing, Chou Teh-Ying, Lee Wen-Chung, Wang Chun-Chieh, Liu Tsang-Wu, Hsia Jiun-Yi, Chang Gee-Chen
Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Division of Pulmonary Medicine, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan.
Front Oncol. 2023 Mar 17;13:1063695. doi: 10.3389/fonc.2023.1063695. eCollection 2023.
Anaplastic lymphoma kinase (ALK) fusion mutation is more common in younger and never-smoking lung cancer patients. The association of smoking and ALK-tyrosine kinase inhibitors (TKIs) on overall survival (OS) of treatment-naïve ALK-positive advanced lung adenocarcinoma remains unclear in real-world.
This retrospective study evaluated all 33170 lung adenocarcinoma patients registered in the National Taiwan Cancer Registry from 2017 to 2019, of whom 9575 advanced stage patients had ALK mutation data.
Among the 9575 patients, 650 (6.8%) patients had ALK mutation with the median follow-up survival time 30.97 months (median age, 62 years; 125 [19.2%] were aged ≥75 years; 357 (54.9%) females; 179 (27.5) smokers, 461 (70.9%) never-smokers, 10 (1.5%) with unknown smoking status; and 544 (83.7%) with first-line ALK-TKI treatment). Overall, of 535 patients with known smoking status who received first-line ALK-TKI treatment, never-smokers and smokers had a median OS of 40.7 months (95% confidence interval (CI), 33.1-47.2 months) and 23.5 months (95% CI, 11.5-35.5 months) (P=0.015), respectively. Among never-smokers, those who received first-line ALK-TKI treatment had a median OS of 40.7 months (95% CI, 22.7-57.8 months), while those ALK-TKI not as first-line treatment had a median OS of 31.7 months (95% CI, 15.2-42.8 months) (P=0.23). In smokers, the median OS for these patients was 23.5 months (95% CI, 11.5-35.5 months) and 15.6 months (95% CI, 10.2-21.1 months) (P=0.026), respectively.
For patients with treatment-naïve advanced lung adenocarcinoma, the ALK test should be performed irrespective of smoking status and age. Smokers had shorter median OS than never-smokers among treatment-naïve-ALK-positive patients with first-line ALK-TKI treatment. Furthermore, smokers not receiving first-line ALK-TKI treatment had inferior OS. Further investigations for the first-line treatment of ALK-positive smoking advanced lung adenocarcinoma patients are needed.
间变性淋巴瘤激酶（ALK）融合突变在年轻且从不吸烟的肺癌患者中更为常见。在现实世界中，吸烟与ALK酪氨酸激酶抑制剂（TKIs）对初治ALK阳性晚期肺腺癌患者总生存期（OS）的影响仍不明确。
这项回顾性研究评估了2017年至2019年在台湾国家癌症登记处登记的所有33170例肺腺癌患者，其中9575例晚期患者有ALK突变数据。
在9575例患者中，650例（6.8%）有ALK突变，中位随访生存时间为30.97个月（中位年龄62岁；125例[19.2%]年龄≥75岁；357例（54.9%）为女性；179例（27.5%）吸烟者，461例（70.9%）从不吸烟者，10例（1.5%）吸烟状态未知；544例（83.7%）接受一线ALK-TKI治疗）。总体而言，在535例已知吸烟状态且接受一线ALK-TKI治疗的患者中，从不吸烟者和吸烟者的中位OS分别为40.7个月（95%置信区间[CI]，33.1 - 47.2个月）和23.5个月（95%CI，11.5 - 35.5个月）（P = 0.015）。在从不吸烟者中，接受一线ALK-TKI治疗的患者中位OS为40.7个月（95%CI，22.7 - 57.8个月），而未接受一线ALK-TKI治疗的患者中位OS为31.7个月（95%CI，15.2 - 42.8个月）（P = 0.23）。在吸烟者中，这些患者的中位OS分别为23.5个月（95%CI，11.5 - 35.5个月）和15.6个月（95%CI，10.2 - 21.1个月）（P = 0.026）。
对于初治晚期肺腺癌患者，无论吸烟状态和年龄如何，都应进行ALK检测。在初治ALK阳性且接受一线ALK-TKI治疗的患者中，吸烟者的中位OS短于从不吸烟者。此外，未接受一线ALK-TKI治疗的吸烟者OS更差。需要对ALK阳性吸烟晚期肺腺癌患者的一线治疗进行进一步研究。
