Moharana Lalatendu, Panda Soumya Surath, Devaraj Suma, Biswas Ghanashyam, Subudhi Ganesh Chandra, Parida Prasant Kumar, Mishra Sourav Kumar, Pattnaik Jogamaya, Mohanty Sambit, Karunanidhi Sukanya, Singuluri Sandhya Lakshmi, Saju S V, Rathnam Krishna Kumar, Sehrawat Amit, Mudgal Shikha, Cyriac Sunu Lazar, Philips Ashwin, Jose Anil Kumar, Ganesan Prasant
Department of Medical Oncology, The Institute of Medical Sciences and SUM Hospital, Bhubaneswar, Odisha, India.
Department of Medical Oncology, Sparsh Hospitals & Critical Care, Bhubaneswar, Odisha, India.
South Asian J Cancer. 2023 Nov 21;13(2):114-120. doi: 10.1055/s-0043-1776290. eCollection 2024 Apr.
Lalatendu Moharana The Anaplastic lymphoma kinase inhibitors (ALKi) represent the standard of care for metastatic non-small cell lung cancer (NSCLC) patients with EML4-ALK rearrangements. Various ALKi agents are available; however, not all eligible patients receive treatment with them due to various reasons. Given the limited real-world data available in our country, we aimed to assess treatment outcomes through a multicenter collaboration. This retrospective, multi-institutional study was conducted under the Network of Oncology Clinical Trials India and included a total of 67 ALK-positive metastatic lung cancer patients from 10 institutes across India, with a median follow-up of 23 months. In the first line setting, the objective response rate (ORR) with ALKi was 63.6% (crizotinib: 60.7%, ceritinib: 70%, alectinib: 66.6%, = 0.508), while with chemotherapy, it was 26.1%. The median progression-free survival (mPFS) for the first line ALKi group was significantly higher than that for chemotherapy (19 vs. 9 months, = 0.00, hazard ratio [HR] = 0.30, 95% confidence interval [CI]: 0.17-0.54). The mPFS for crizotinib, alectinib, and ceritinib was 17, 22, and 19 months, respectively ( = 0.48). Patients who received ALKi upfront or after 1 to 3 cycles of chemotherapy or after 4 or more cycles of chemotherapy had mPFS of 16, 22, and 23 months, respectively ( = 0.47). ALKi showed superior mPFS compared to chemotherapy in the second line (14 vs. 5 months; = 0.002) and the third line (20 vs. 4 months; = 0.009). The median overall survival (OS) was significantly better in patients who received ALKi in any line of therapy (44 vs. 14 months, < 0.001, HR = 0.10, 95% CI: 0.04-0.23). Brain progression was higher among those who did not receive ALKi (69.2 vs. 31.5%). In conclusion, the use of ALKi as first line treatment for ALK-positive metastatic NSCLC patients resulted in improved PFS. PFS and ORR did not significantly differ between patients who received ALKi upfront or after initiating chemotherapy. Notably, patients who received ALKi in second or later lines demonstrated significantly better outcomes compared to those receiving chemotherapy. The use of ALKi in any line of therapy was associated with significantly prolonged OS.
拉拉滕杜·莫哈纳纳 间变性淋巴瘤激酶抑制剂（ALKi）是具有EML4-ALK重排的转移性非小细胞肺癌（NSCLC）患者的标准治疗方案。有多种ALKi药物可供使用；然而，由于各种原因，并非所有符合条件的患者都接受这些药物治疗。鉴于我国可用的真实世界数据有限，我们旨在通过多中心合作评估治疗结果。这项回顾性、多机构研究是在印度肿瘤临床试验网络下进行的，共纳入了来自印度各地10家机构的67例ALK阳性转移性肺癌患者，中位随访时间为23个月。在一线治疗中，ALKi的客观缓解率（ORR）为63.6%（克唑替尼：60.7%，色瑞替尼：70%，阿来替尼：66.6%，P=0.508），而化疗的ORR为26.1%。一线ALKi组的中位无进展生存期（mPFS）显著高于化疗组（19个月对9个月，P=0.00，风险比[HR]=0.30，95%置信区间[CI]：0.17-0.54）。克唑替尼、阿来替尼和色瑞替尼的mPFS分别为17个月、22个月和19个月（P=0.48）。接受一线ALKi治疗、化疗1至3个周期后或化疗4个或更多周期后接受ALKi治疗的患者，其mPFS分别为16个月、22个月和23个月（P=0.47）。在二线治疗（14个月对5个月；P=0.002）和三线治疗（20个月对4个月；P=0.009）中，ALKi的mPFS均优于化疗。在任何一线治疗中接受ALKi治疗的患者的中位总生存期（OS）显著更好（44个月对14个月，P<0.001，HR=0.10，95%CI：0.04-0.23）。未接受ALKi治疗的患者脑转移发生率更高（69.2%对31.5%）。总之，将ALKi作为ALK阳性转移性NSCLC患者的一线治疗可改善无进展生存期。接受一线ALKi治疗或化疗开始后接受ALKi治疗的患者的无进展生存期和客观缓解率无显著差异。值得注意的是，在二线或更晚线接受ALKi治疗的患者与接受化疗的患者相比，预后明显更好。在任何一线治疗中使用ALKi均与显著延长总生存期相关。
