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Table of Contents
Year : 2021  |  Volume : 4  |  Issue : 2  |  Page : 422-423

Authors' reply to Shah et al.

1 Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India
2 Department of Medical Oncology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India

Date of Submission02-Jun-2021
Date of Decision02-Jun-2021
Date of Acceptance03-Jun-2021
Date of Web Publication30-Jun-2021

Correspondence Address:
Ullas Batra
Sector 5 Rohini, Sir Chhotu Ram Marg, New Delhi - 110 085
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/crst.crst_130_21

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How to cite this article:
Nathany S, Batra U. Authors' reply to Shah et al. Cancer Res Stat Treat 2021;4:422-3

How to cite this URL:
Nathany S, Batra U. Authors' reply to Shah et al. Cancer Res Stat Treat [serial online] 2021 [cited 2021 Oct 22];4:422-3. Available from: https://www.crstonline.com/text.asp?2021/4/2/422/320311

We thank Shah et al.[1] for their comments on our article titled, “NTRK-A narrative review.”[2] Non-small-cell lung cancer (NSCLC) has emerged as a molecularly heterogeneous disease, and NTRK fusions have gained importance owing to the development and efficacy of entrectinib and larotrectinib, which are approved for NTRK fusion-positive cancers, and the advent of newer drugs such as repotrectinib and selitrectinib that are awaiting approvals.[3],[4] The European Society for Medical Oncology recommendations[5] for NTRK testing have lucidly described the use of immunohistochemistry, fluorescence in situ hybridization, reverse-transcription polymerase chain reaction, and next-generation sequencing (NGS) in specific situations. However, as has been reported by several studies, performing panel-based NGS not only overcomes the issues related to tissue availability, which is often limited in the case of lung cancer but also offers higher throughput and sensitivity. Although NGS facilities may not be available in resource-constrained settings, with continuous technological advances and as depicted by Moore's law, the cost of NGS has reduced since its inception.[6] NTRK fusions can mediate resistance to EGFR tyrosine kinase inhibitors, similar to ALK, RET, and ROS1 fusions, which have been reported to cause resistance in EGFR-positive NSCLCs treated with osimertinib.

With respect to immunotherapy and resistance to the programmed death-ligand 1 axis, Farago and Azzoli in their study on a large Chinese cohort reported similar frequencies of occurrence of STK11 in these cases when comparing NSCLC as a whole including other histologic subtypes; however, this frequency was lower in the adenocarcinoma subgroup.[7] Therefore, the authors concluded that patients with NTRK fusion-positive NSCLCs may benefit from immunotherapy, which usually has a lower efficacy in other oncogene-driven subtypes. Thus, even though NTRK fusions are rare, it is important to look for this fusion in all settings, especially when the patient has exhausted other lines of therapy.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Shah M, Abraham G, Menon N. Clinical utility of the NTRK gene fusions in current clinical practice. Cancer Res Stat Treat 2021;4:420-2.  Back to cited text no. 1
  [Full text]  
Batra U, Nathany S, Sharma M. NTRK-A narrative review. Cancer Res Stat Treat 2021;4:110-4.  Back to cited text no. 2
  [Full text]  
Zito Marino F, Pagliuca F, Ronchi A, Cozzolino I, Montella M, Berretta M, et al. NTRK Fusions, from the diagnostic algorithm to innovative treatment in the era of precision medicine. Int J Mol Sci 2020;21:3718.  Back to cited text no. 3
Laetsch TW, DuBois SG, Mascarenhas L, Turpin B, Federman N, Albert CM, et al. Larotrectinib for paediatric solid tumours harbouring NTRK gene fusions: Phase 1 results from a multicentre, open-label, phase 1/2 study. Lancet Oncol 2018;19:705-14.  Back to cited text no. 4
Marchiò C, Scaltriti M, Ladanyi M, Iafrate AJ, Bibeau F, Dietel M, et al. ESMO recommendations on the standard methods to detect NTRK fusions in daily practice and clinical research. Ann Oncol 2019;30:1417-27.  Back to cited text no. 5
Muir P, Li S, Lou S, Wang D, Spakowicz DJ, Salichos L, et al. The real cost of sequencing: Scaling computation to keep pace with data generation. Genome Biol 2016;17:1-9.  Back to cited text no. 6
Farago AF, Azzoli CG. Beyond ALK and ROS1: RET, NTRK, EGFR and BRAF gene rearrangements in non-small cell lung cancer. Transl Lung Cancer Res 2017;6:550-9.  Back to cited text no. 7


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