Download PDF
CC BY-NC-ND 4.0 · South Asian J Cancer 2024; 13(02): 114-120
DOI: 10.1055/s-0043-1776290
Original Article
Lung Cancer

Real-World Data on Treatment Outcome of ALK-Positive Non-Small Cell Lung Cancer from an Indian Multicentric Cancer Registry

Lalatendu Moharana 
1   Department of Medical Oncology, The Institute of Medical Sciences and SUM Hospital, Bhubaneswar, Odisha, India
,
Soumya Surath Panda
1   Department of Medical Oncology, The Institute of Medical Sciences and SUM Hospital, Bhubaneswar, Odisha, India
,
Suma Devaraj
1   Department of Medical Oncology, The Institute of Medical Sciences and SUM Hospital, Bhubaneswar, Odisha, India
,
Ghanashyam Biswas
2   Department of Medical Oncology, Sparsh Hospitals & Critical Care, Bhubaneswar, Odisha, India
,
Ganesh Chandra Subudhi
2   Department of Medical Oncology, Sparsh Hospitals & Critical Care, Bhubaneswar, Odisha, India
,
Prasant Kumar Parida
3   Department of Medical Oncology, Acharya Harihar Post Graduate Institute of Cancer, Cuttack, Odisha, India
,
Sourav Kumar Mishra
4   Department of Medical Oncology, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India
,
Jogamaya Pattnaik
4   Department of Medical Oncology, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India
5   Department of Medical Oncology, Kalinga Institute of Medical Sciences, Bhubaneswar, Odisha, India
,
Sambit Mohanty 
6   Department of Pathology, Advanced Medicare & Research Institute, Bhubaneswar, Odisha, India
,
Sukanya Karunanidhi
7   Department of Medical Oncology, Jawaharlal Institute of Postgraduate Medical Education & Research, Puducherry, India
,
Sandhya Lakshmi Singuluri
7   Department of Medical Oncology, Jawaharlal Institute of Postgraduate Medical Education & Research, Puducherry, India
,
S. V. Saju 
8   Department of Haematology and Medical Oncology, Meenakshi Mission Hospital and Research Centre, Madurai, Tamil Nadu, India
,
Krishna Kumar Rathnam
8   Department of Haematology and Medical Oncology, Meenakshi Mission Hospital and Research Centre, Madurai, Tamil Nadu, India
,
Amit Sehrawat 
9   Department of Medical Oncology, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India
,
Shikha Mudgal
9   Department of Medical Oncology, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India
,
Sunu Lazar Cyriac
10   Department of Medical Oncology, Amala Institute of Medical Sciences, Thrissur, Kerala, India
,
Ashwin Philips
11   Christian Medical College Hospital, Ludhiana, Punjab, India
,
Anil Kumar Jose
10   Department of Medical Oncology, Amala Institute of Medical Sciences, Thrissur, Kerala, India
,
Prasant Ganesan 
12   Department of Medical Oncology, Jawaharlal Institute of Postgraduate Medical Education & Research, Puducherry, India
› Author Affiliations Funding The salary for the data entry operators and the biostatistician involved in collecting and analyzing this data was supported by a Biotechnology Industry Research Assistance Council, India (BIRAC) grant through the National Biopharma Mission.
› Further Information
Also available at
   Permissions and Reprints

Abstract

Zoom Image
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%, p = 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, p = 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 (p = 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 (p = 0.47). ALKi showed superior mPFS compared to chemotherapy in the second line (14 vs. 5 months; p = 0.002) and the third line (20 vs. 4 months; p = 0.009). The median overall survival (OS) was significantly better in patients who received ALKi in any line of therapy (44 vs. 14 months, p < 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.

Keywords

real-world data - anaplastic lymphoma kinase - non-small cell lung cancer

Note

Clinical Trials Registry-India (CTRI) Number: CTRI/2022/01/039233.




Publication History

Article published online:
21 November 2023

© 2023. MedIntel Services Pvt Ltd. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India

 

  • References

  • 1 Barlesi F, Mazieres J, Merlio JP. et al; Biomarkers France contributors. Routine molecular profiling of patients with advanced non-small-cell lung cancer: results of a 1-year nationwide programme of the French Cooperative Thoracic Intergroup (IFCT). Lancet 2016; 387 (10026): 1415-1426
    CrossrefPubMedGoogle Scholar
  • 2 Lee B, Lee T, Lee SH, Choi YL, Han J. Clinicopathologic characteristics of EGFR, KRAS, and ALK alterations in 6,595 lung cancers. Oncotarget 2016; 7 (17) 23874-23884
    CrossrefPubMedGoogle Scholar
  • 3 Vidal J, Clavé S, de Muga S. et al. Assessment of ALK status by FISH on 1000 Spanish non-small cell lung cancer patients. J Thorac Oncol 2014; 9 (12) 1816-1820
    CrossrefPubMedGoogle Scholar
  • 4 Le T, Gerber DE. ALK alterations and inhibition in lung cancer. Semin Cancer Biol 2017; 42: 81-88
    CrossrefPubMedGoogle Scholar
  • 5 Di Maio M, De Marinis F, Hirsch FR, Gridelli C. Diagnostic and therapeutic issues for patients with advanced non–small cell lung cancer harboring anaplastic lymphoma kinase rearrangement: European vs. US perspective (review). Int J Oncol 2014; 45 (02) 509-515
    CrossrefPubMedGoogle Scholar
  • 6 Tang H, Jin L, Zhang Z, Jiang Z, Malik Z. Comparison of clinical efficacy of alectinib versus crizotinib in ALK-positive non-small cell lung cancer: a meta-analysis. Front Oncol 2021; 11: 646526
    CrossrefPubMedGoogle Scholar
  • 7 Elliott J, Bai Z, Hsieh SC. et al. ALK inhibitors for non-small cell lung cancer: a systematic review and network meta-analysis. PLoS One 2020; 15 (02) e0229179
    CrossrefPubMedGoogle Scholar
  • 8 Qian M, Zhu B, Wang X, Liebman M. Drug resistance in ALK-positive non-small cell lung cancer patients. Semin Cell Dev Biol 2017; 64: 150-157
    CrossrefPubMedGoogle Scholar
  • 9 Pikor LA, Ramnarine VR, Lam S, Lam WL. Genetic alterations defining NSCLC subtypes and their therapeutic implications. Lung Cancer 2013; 82 (02) 179-189
    CrossrefPubMedGoogle Scholar
  • 10 Martelli MP, Sozzi G, Hernandez L. et al. EML4-ALK rearrangement in non-small cell lung cancer and non-tumor lung tissues. Am J Pathol 2009; 174 (02) 661-670
    CrossrefPubMedGoogle Scholar
  • 11 Boland JM, Erdogan S, Vasmatzis G. et al. Anaplastic lymphoma kinase immunoreactivity correlates with ALK gene rearrangement and transcriptional up-regulation in non-small cell lung carcinomas. Hum Pathol 2009; 40 (08) 1152-1158
    CrossrefPubMedGoogle Scholar
  • 12 Shaw AT, Yeap BY, Mino-Kenudson M. et al. Clinical features and outcome of patients with non-small-cell lung cancer who harbor EML4-ALK. J Clin Oncol 2009; 27 (26) 4247-4253
    CrossrefPubMedGoogle Scholar
  • 13 Inamura K, Takeuchi K, Togashi Y. et al. EML4-ALK fusion is linked to histological characteristics in a subset of lung cancers. J Thorac Oncol 2008; 3 (01) 13-17
    CrossrefPubMedGoogle Scholar
  • 14 Solomon B, Varella-Garcia M, Camidge DR. ALK gene rearrangements: a new therapeutic target in a molecularly defined subset of non-small cell lung cancer. J Thorac Oncol 2009; 4 (12) 1450-1454
    CrossrefPubMedGoogle Scholar
  • 15 Crizotinib capsules. Accessed October 5, 2023 at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/202570s021lbl.pdf
  • 16 Wong DWS, Leung ELH, So KKT. et al; University of Hong Kong Lung Cancer Study Group. The EML4-ALK fusion gene is involved in various histologic types of lung cancers from nonsmokers with wild-type EGFR and KRAS. Cancer 2009; 115 (08) 1723-1733
    CrossrefPubMedGoogle Scholar
  • 17 Lung and Bronchus Cancer—Cancer Stat Facts. Accessed October 5, 2023 at: https://seer.cancer.gov/statfacts/html/lungb.html
  • 18 Travis WD, Brambilla E, Noguchi M. et al. International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society International Multidisciplinary Classification of Lung Adenocarcinoma. J Thorac Oncol 2011; 6 (02) 244-285
    CrossrefPubMedGoogle Scholar
  • 19 Hayashi H, Kitamura H, Nakatani Y, Inayama Y, Ito T, Kitamura H. Primary signet-ring cell carcinoma of the lung: histochemical and immunohistochemical characterization. Hum Pathol 1999; 30 (04) 378-383
    CrossrefPubMedGoogle Scholar
  • 20 Camidge DR, Dziadziuszko R, Peters S. et al. Updated efficacy and safety data and impact of the EML4-ALK fusion variant on the efficacy of alectinib in untreated ALK-positive advanced non-small cell lung cancer in the global phase III ALEX study. J Thorac Oncol 2019; 14 (07) 1233-1243
    CrossrefPubMedGoogle Scholar
  • 21 Camidge DR, Kim HR, Ahn MJ. et al. Brigatinib versus crizotinib in ALK-positive non-small-cell lung cancer. N Engl J Med 2018; 379 (21) 2027-2039
    CrossrefPubMedGoogle Scholar
  • 22 Camidge DR, Kim HR, Ahn MJ. et al. Brigatinib versus crizotinib in ALK inhibitor-naive advanced ALK-positive NSCLC: final results of phase 3 ALTA-1L trial. J Thorac Oncol 2021; 16 (12) 2091-2108
    CrossrefPubMedGoogle Scholar
  • 23 Shaw AT, Bauer TM, de Marinis F. et al; CROWN Trial Investigators. First-line lorlatinib or crizotinib in advanced ALK-positive lung cancer. N Engl J Med 2020; 383 (21) 2018-2029
    CrossrefPubMedGoogle Scholar
  • 24 Soria JC, Tan DSW, Chiari R. et al. First-line ceritinib versus platinum-based chemotherapy in advanced ALK-rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study. Lancet 2017; 389 (10072): 917-929
    CrossrefPubMedGoogle Scholar
  • 25 Solomon BJ, Mok T, Kim DW. et al; PROFILE 1014 Investigators. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med 2014; 371 (23) 2167-2177
    CrossrefPubMedGoogle Scholar
  • 26 Peters S, Camidge DR, Shaw AT. et al; ALEX Trial Investigators. Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer. N Engl J Med 2017; 377 (09) 829-838
    CrossrefPubMedGoogle Scholar
  • 27 Patel A, Batra U, Prasad KT. et al. Real world experience of treatment and outcome in ALK-rearranged metastatic nonsmall cell lung cancer: a multicenter study from India. Curr Probl Cancer 2020; 44 (03) 100571
    CrossrefPubMedGoogle Scholar
  • 28 Noronha V, Ramaswamy A, Patil VM. et al. ALK positive lung cancer: clinical profile, practice and outcomes in a developing country. PLoS One 2016; 11 (09) e0160752 DOI: 10.1371/journal.pone.0160752. Erratum in: PLoS One. 2016 Dec 9;11(12): e0168221
    CrossrefPubMedGoogle Scholar