• Users Online: 853
  • Print this page
  • Email this page

Table of Contents
Year : 2020  |  Volume : 3  |  Issue : 2  |  Page : 403-404

Anaplastic lymphoma kinase-positive metastatic non-small-cell lung cancer: Emerging resistance and treatment options

1 Department of Medicine, Santosh Medical College, Ghaziabad, Uttar Pradesh, India
2 Department of Medical Oncology, Army Hospital Research and Referral, New Delhi, India

Date of Submission08-Mar-2020
Date of Acceptance09-Mar-2020
Date of Web Publication19-Jun-2020

Correspondence Address:
Amba Prasad Dubey
Department of Medicine, Santosh Medical College, Ghaziabad, Uttar Pradesh
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/CRST.CRST_72_20

Get Permissions

How to cite this article:
Dubey AP, Swamy S, Rathore A, Kaushik M R. Anaplastic lymphoma kinase-positive metastatic non-small-cell lung cancer: Emerging resistance and treatment options. Cancer Res Stat Treat 2020;3:403-4

How to cite this URL:
Dubey AP, Swamy S, Rathore A, Kaushik M R. Anaplastic lymphoma kinase-positive metastatic non-small-cell lung cancer: Emerging resistance and treatment options. Cancer Res Stat Treat [serial online] 2020 [cited 2021 Jul 27];3:403-4. Available from: https://www.crstonline.com/text.asp?2020/3/2/403/287263

I congratulate the authors for the interesting narration of the course of anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer patients on ALK inhibitors.[1] In the era of genomic sequencing, it is very common to stumble upon varied types of mutations. Molecular tumor boards will be of great help in choosing patients who may benefit from genomic sequencing, understanding the importance of these mutations and choosing appropriate therapy.

ALK-positive lung cancer patients in the Indian scenario constitute 4%–5% of adenocarcinoma lung cancer patients. Although alectinib has clearly demonstrated prolongation of the median progression-free survival to 34.1 months in these patients,[2] its use in the first-line setting in resource-limited situations is not feasible.[3] In these situations, sequencing of ALK inhibitors and understanding the mechanism of resistance are of paramount importance.

The site of progression in ALK-positive lung cancer patients on crizotinib is the first crucial information. Intracranial progression is the major reason for failure, accounting for approximately 30% of cases.[4] The reason for these failures is the decreased central nervous system penetration of crizotinib. The role of genomic sequencing either with liquid biopsy or stereotactic brain biopsy is questionable.

However, in extracranial progression, like in this patient, the chances of acquired resistance to crizotinib are high. The mechanisms of resistance may be additional mutations in the ALK gene altering its drug-binding capacity or oncogenic bypass through activation of MET, ERBB2, or other pathways. In these subsets of patients, the case should be discussed in the molecular tumor boards and the utility of genomic sequencing should be discussed. Genomic sequencing will not only help in choosing further therapy but may also help in understanding the resistance pattern.

Second, I would like to emphasize the role of local therapy such as stereotactic body radiotherapy (SBRT) in oligoprogressive disease, like in this patient. SBRT to sites of oligoprogression may possibly eliminate the resistant clone and result in the opportunity to continue the same systemic therapy.[5] Though in the era of availability of newer ALK inhibitors, the role of local therapy is not clearly known, it merits consideration.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Kapoor A, Noronha V, Shetty O, Chougule A, Chandrani P, Patil VM, et al. Molecular tumor board: Case 2 – Evolution of resistance in anaplastic lymphoma kinase driven non-small-cell lung carcinoma. Cancer Res Stat Treat 2020;3:89.  Back to cited text no. 1
  [Full text]  
Nakagawa K, Hida T, Nokihara H, Morise M, Azuma K, Kim YH, et al. Final progression-free survival results from the J-ALEX study of alectinib versus crizotinib in ALK-positive non-small-cell lung cancer. Lung Cancer 2020;139:195-9.  Back to cited text no. 2
Philip CC, Mathew A, John MJ. Cancer care: Challenges in the developing world. Cancer Res Stat Treat 2018;1:58-62.  Back to cited text no. 3
  [Full text]  
Solomon BJ, Mok T, Kim DW, Wu YL, Nakagawa K, Mekhail T, et al. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med 2014;371:2167-77.  Back to cited text no. 4
Weickhardt AJ, Scheier B, Burke JM, Gan G, Lu X, Bunn PA Jr., et al. Local ablative therapy of oligoprogressive disease prolongs disease control by tyrosine kinase inhibitors in oncogene-addicted non-small-cell lung cancer. J Thorac Oncol 2012;7:1807-14.  Back to cited text no. 5

This article has been cited by
1 Authorsę reply to Dubey et al. and Bhattacharyya et al.
Akhil Kapoor,Vanita Noronha,Omshree Shetty,Anuradha Chougule,Pratik Chandrani,VijayM Patil,Amit Joshi,Nandini Menon,Rajiv Kumar,Mamta Gurav,Amit Kumar,Kumar Prabhash
Cancer Research, Statistics, and Treatment. 2020; 3(2): 406
[Pubmed] | [DOI]


    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

  In this article

 Article Access Statistics
    PDF Downloaded48    
    Comments [Add]    
    Cited by others 1    

Recommend this journal