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Front. Oncol. | doi: 10.3389/fonc.2018.00557

ALK inhibitors in the treatment of ALK positive NSCLC

 Muhammad Khan1, 2, Jie Lin1, Guixiang Liao1, Yunhong Tian1, Yingying Liang1, Rong Li1, Mengzhong Liu1, 3 and Yawei Yuan1, 3*
  • 1Guangzhou Medical University Cancer Hospital, China
  • 2Anhui Medical University, China
  • 3Sun Yat-sen University Cancer Center (SYSUCC), China

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.

Methods & Materials: 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 11 studies (n=3022) 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 and alectinib) revealed significant improvement in PFS (HR 0.50 [0.43, 0.58; p<0.00001]), ORR (OR 1.56 [1.15, 2.11; p=0.004] in comparison to crizotinib. Alectinib yielded better response intra-cranially than crizotinib. 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, Alectinib is safer and more effective intra-cranially and can be preferred as first option.

Keywords: ALK, anaplastic lymphoma kinase, NSCLC (non small cell lung cancer), Molecular tagetd agent, Chemotherapy (CH), Progression free survival (PFS), Quality of Life

Received: 16 Oct 2018; Accepted: 09 Nov 2018.

Edited by:

Alfredo Addeo, Geneva University Hospitals (HUG), Switzerland

Reviewed by:

Giulio Metro, Ospedale Santa Maria della Misericordia di Perugia, Italy
Antonio Passaro, Istituto Europeo di Oncologia s.r.l., Italy
Petra J. Jankowska, Taunton and Somerset, NHS Foundation Trust, United Kingdom  

Copyright: © 2018 Khan, Lin, Liao, Tian, Liang, Li, Liu and Yuan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Yawei Yuan, Guangzhou Medical University Cancer Hospital, Guangzhou, Guangdong Province, China, yuanyawei2015@outlook.com