Dataset Information

Impact of ALK variants on brain metastasis and treatment response in advanced NSCLC patients with oncogenic ALK fusion.

ABSTRACT: Background:To investigate the impact of ALK variants on the features of brain metastases (BM), the outcome of chemotherapy and targeted therapy using crizotinib, as well as the progression pattern in patients with ALK fusion. Methods:Patients with ALK fusion were retrospectively collected from January 2013 to July 2017 in Shanghai Pulmonary Hospital. ALK rearrangements were identified via ARMS-PCR. ALK variants were identified via Sanger Sequencing. Results:A total of 135 patients and 41 with brain metastasis were identified. Radiological features showed that the patients with ALK variant 1 had a larger BM size compared with patients with ALK non-variant 1 (median tumor size: 16.89 vs. 11.01 mm, P=0.031). Similar time to treatment failure (TTF) was observed in patients with ALK variant 1 and non-variant 1 who received first-line crizotinib (median TTF: 15.7 vs. 13.8 months, HR =0.75, P=0.34). Patients with ALK variant 1 who had baseline BM had significantly shorter TTF than non-variant 1 with baseline BM when treated with first-line crizotinib (median TTF: 9.1 vs. 14.9 months, HR =2.68, P=0.037). In patients treated with chemotherapy, ALK variant 1 was associated with inferior TTF (median TTF: 5.6 vs. 8.1 months, HR =1.66, P=0.039). Progression pattern was similar between ALK variant 1 and non-variant 1. Conclusions:Patients with ALK variant 1 and baseline BM had inferior TTF on first-line crizotinib treatment and presented with more aggressive radiological features. Patients with ALK non-variant 1 had better clinical outcome on first-line chemotherapy.

SUBMITTER: Qiao M

PROVIDER: S-EPMC7481619 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Impact of ALK variants on brain metastasis and treatment response in advanced NSCLC patients with oncogenic ALK fusion.

Qiao Meng M Zhao Chao C Liu Qian Q Wang Yan Y Shi Jingyun J Ng Terry L TL Zhou Fei F Li Xuefei X Jiang Tao T Yang Shuo S Gao Guanghui G Xiong Anwen A Li Jiayu J Li Wei W Wu Fengying F Chen Xiaoxia X Su Chunxia C Ren Shengxiang S Zhou Caicun C Zhang Jun J

Translational lung cancer research 20200801 4

<h4>Background</h4>To investigate the impact of ALK variants on the features of brain metastases (BM), the outcome of chemotherapy and targeted therapy using crizotinib, as well as the progression pattern in patients with ALK fusion.<h4>Methods</h4>Patients with ALK fusion were retrospectively collected from January 2013 to July 2017 in Shanghai Pulmonary Hospital. ALK rearrangements were identified via ARMS-PCR. ALK variants were identified via Sanger Sequencing.<h4>Results</h4>A total of 135 p ...[more]

PMID: 32953517

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Project description:Background: ALK inhibitors have shown positive advance in the treatment of ALK+ NSCLC. They have achieved better results in prolonging the progression free survival and improving quality of life in comparison to chemotherapy. We have assembled the evidence related to the efficacy and safety of these agents in the treatment of ALK positive NSCLC. Materials and Methods: A comprehensive search was conducted using electronic databases of PubMed, Medline and Cochrane Library to identify the studies involving comparison of ALK inhibitors to chemotherapy and Next generation ALK inhibitors to crizotinib. PFS was the primary outcome while other outcomes like ORR, adverse events, quality of life and OS were also analyzed and compared. Hazard ratios and odds ratios obtained were analyzed using fixed effect or random effects model in Review Manager Software. Results: A total of 12 studies (n = 3,297) met the criteria for inclusion in this review and meta-analysis. ALK inhibitors including crizotinib, ceritinib and alectinib revealed significantly better PFS (HR 0.42 [0.35, 0.50; p < 0.00001]), ORR (Overall OR 6.59 [4.86, 8.94; p < 0.00001] as compared to chemotherapy in the first line as well as second line treatment settings. Intracranial response rate was better with ALK inhibitors (ceritinib and alectinib) as compared to chemotherapy OR 6.51 [2.86, 14.83; p < 0.00001]. No significant increase in grade 3 or 4 adverse events was observed with crizotinib (OR 1.21 [0.82, 1.77; p = 0.34]) or ceritinib (OR 1.49 [0.86, 2.57; p = 0.17]) when compared to chemotherapy individually. Quality of life indicators assessed were significantly improved with ALK inhibitors. Next generation agents (ceritinib, alectinib and brigatinib) revealed significant improvement in PFS (HR 0.50 [0.43, 0.57; p < 0.00001]), ORR (OR 1.57 [1.21, 2.04; p = 0.0006]) in comparison to crizotinib. Next generation agents (Alectinib and brigatinib) yielded better response intra-cranially than crizotinib in terms of objective response rate (OR 5.87 [3.49, 9.87; p < 0.00001]) and time to CNS progression (HR 0.25 [0.13, 0.46; p < 0.0001]). Alectinib by far resulted in fewer adverse events than chemotherapy or crizotinib. Conclusions: Overall ALK inhibitors are safe and effective treatment option in ALK+ non-small cell lung cancer. Of the ALK inhibitors, Next generation agents in particular alectinib and brigatinib are safer and more effective intra-cranially and can be preferred as first option.

Dataset Information

Impact of ALK variants on brain metastasis and treatment response in advanced NSCLC patients with oncogenic ALK fusion.

Publications

Impact of ALK variants on brain metastasis and treatment response in advanced NSCLC patients with oncogenic ALK fusion.

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