Predictive biomarkers in nonsmall cell carcinoma and their clinico-pathological association

Anurag Mehta; Nayana N. Sriramanakoppa; Poojan Agarwal; Gayatri Viswakarma; Smreti Vasudevan; Manoj Panigrahi; Dushyant Kumar; Mumtaz Saifi; Irfan Chowdhary; D.C Doval; Moushumi Suryavanshi

doi:10.4103/sajc.sajc_373_18

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ORIGINAL ARTICLE: Lung Cancers

08 (

); 250-254

doi:

10.4103/sajc.sajc_373_18

Predictive biomarkers in nonsmall cell carcinoma and their clinico-pathological association

Anurag Mehta¹, Nayana N. Sriramanakoppa², Poojan Agarwal^2,, Gayatri Viswakarma³, Smreti Vasudevan³, Manoj Panigrahi⁴, Dushyant Kumar⁴, Mumtaz Saifi⁴, Irfan Chowdhary², D.C Doval^4,5, Moushumi Suryavanshi⁴

1 Department of Lab Services, Transfusion Medicine and Molecular Diagnostics, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi

2 Department of Laboratory Services and Transfusion Medicine, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi

3 Department of Research, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi

4 Department of Molecular Diagnostics and Cell Biology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi

5 Department of Medical Oncology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi

*Corresponding author: Dr. Poojan Agarwal. poojanagarwal@gmail.com

Published: 2020-12-14

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/.)

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This article was originally published by Thieme Medical and Scientific Publishers Pvt. Ltd. and was migrated to Scientific Scholar after the change of Publisher.

Abstract

Background: Lung cancer is the leading cause of cancer-related mortality worldwide. Genome-directed therapy is less toxic, prolongs survival and provides a better quality of life. Predictive biomarker testing, therefore, has become a standard of care in advanced lung cancers. The objective of this study was to relate clinical and pathological features, including response to targeted therapy (TT) and progression-free survival (PFS) with positive driver mutation. Materials and Methods: Archival data of nonsmall cell carcinoma patients with Stage IV disease were retrieved. Those who tested positive for one of the four biomarkers (epidermal growth factor receptor [EGFR], anaplastic lymphoma kinase [ALK], MET, and ROS) were included. Patient demographics and clinical features were reviewed. Tumor histomorphology was correlated with oncological drivers. Treatment response, PFS, and overall survival were studied in three subcohorts of patients who received computed tomography (CT), CT followed by TT and those who received TT in the first line. Results: A total of 900 patients underwent biomarker evaluation of which 288 tested positive. Frequency of the four biomarkers observed was 26.6% (229/860), 6.6% (51/775), 6.6% (5/75), and 5.1% (3/59) for EGFR, ALK, MET, and ROS-1, respectively. The median PFS for EGFR-mutated cohort was 12 months, whereas it was 21 months for ALK protein overexpressing cases. Patients treated with first-line tyrosine kinase inhibitors performed better compared to those who were switched from chemotherapy to TT or those who received chemotherapy alone (P < 0.05). Conclusion: Biomarker testing has improved patient outcome. Genome-directed therapy accords best PFS with an advantage of nearly 10 months over cytotoxic therapy.

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References

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Su S, Hu Y, Ouyang W, Ma Z, Lu B, Li Q, et al. The survival outcomes and prognosis of stage IV non-small-cell lung cancer treated with thoracic three-dimensional radiotherapy combined with chemotherapy. Radiat Oncol 2014;9:290.
Ramlau R, Gorbunova V, Ciuleanu TE, Novello S, Ozguroglu M, Goksel T, et al. Aflibercept and docetaxel versus docetaxel alone after platinum failure in patients with advanced or metastatic non-small-cell lung cancer: A randomized, controlled phase III trial. J Clin Oncol 2012;30:3640-7.
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Kota R, Gundeti S, Gullipalli M, Linga VG, Maddali LS, Digumarti R, et al. Prevalence and outcome of epidermal growth factor receptor mutations in non-squamous non-small cell lung cancer patients. Lung India 2015;32:561-5.
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Inoue A, Yoshida K, Morita S, Imamura F, Seto T, Okamoto I, et al. Characteristics and overall survival of EGFR mutation-positive non-small cell lung cancer treated with EGFR tyrosine kinase inhibitors: A retrospective analysis for 1660 Japanese patients. Jpn J Clin Oncol 2016;46:462-7.
Shi Y, Au JS, Thongprasert S, Srinivasan S, Tsai CM, Khoa MT, et al. A prospective, molecular epidemiology study of EGFR mutations in Asian patients with advanced non-small-cell lung cancer of adenocarcinoma histology (PIONEER). J Thorac Oncol 2014;9:154-62.
Choi YL, Sun JM, Cho J, Rampal S, Han J, Parasuraman B, et al. EGFR mutation testing in patients with advanced non-small cell lung cancer: A comprehensive evaluation of real-world practice in an East Asian tertiary hospital. PLoS One 2013;8:e56011.
Choughule A, Noronha V, Joshi A, Desai S, Jambhekar N, Utture S, et al. Epidermal growth factor receptor mutation subtypes and geographical distribution among Indian non-small cell lung cancer patients. Indian J Cancer 2013;50:107-11.
Mehta J. Molecular epidemiology of epidermal growth factor receptor mutations in lung cancers in Indian population. Indian J Cancer 2013;50:102-6.
Greenhalgh J, Dwan K, Boland A, et al. First line treatment of epidermal growth factor receptor (EGFR) mutation positive non-squamous non-small cell lung cancer. Cochrane Database Syst Rev 2016;5:CD010383.
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Song Z, Zhu H, Guo Z, Wu W, Sun W, Zhang Y, et al. Correlation of EGFR mutation and predominant histologic subtype according to the new lung adenocarcinoma classification in Chinese patients. Med Oncol 2013;30:645.
Villa C, Cagle PT, Johnson M, Patel JD, Yeldandi AV, Raj R, et al. Correlation of EGFR mutation status with predominant histologic subtype of adenocarcinoma according to the new lung adenocarcinoma classification of the international association for the study of lung cancer/American Thoracic Society/European Respiratory Society. Arch Pathol Lab Med 2014;138:1353-7.
Noronha V, Ramaswamy A, Patil VM, Joshi A, Chougule A, Kane S, et al. ALK positive lung cancer: Clinical profile, practice and outcomes in a developing country. PLoS One 2016;11:e0160752.
Shaw AT, Yeap BY, Solomon BJ, Riely GJ, Gainor J, Engelman JA, et al. Effect of crizotinib on overall survival in patients with advanced non-small-cell lung cancer harbouring ALK gene rearrangement: A retrospective analysis. Lancet Oncol 2011;12:1004-12.
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[1] Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC Cancer Base No. 11. Lyon, France: International Agency for Research on Cancer; 2013. Available from: http://www.globocan.iarc.fr. [Last accessed on 2014 Jan 21].

[2] Malik PS, Raina V. Lung cancer: Prevalent trends & emerging concepts. Indian J Med Res 2015;141:5-7.

[3] Kamath MP, Lakshmaiah KC, Babu KG, Loknatha D, Jacob LA, Babu SM, et al. Pharmacoeconomic benefit of cisplatin and etoposide chemoregimen for metastatic non small cell lung cancer: An Indian study. Lung India 2016;33:154-8.

[4] Liang B, Shao Y, Long F, Jiang SJ. Predicting diagnostic gene biomarkers for non-small-cell lung cancer. Biomed Res Int 2016;2016:3952494.

[5] Su S, Hu Y, Ouyang W, Ma Z, Lu B, Li Q, et al. The survival outcomes and prognosis of stage IV non-small-cell lung cancer treated with thoracic three-dimensional radiotherapy combined with chemotherapy. Radiat Oncol 2014;9:290.

[6] Ramlau R, Gorbunova V, Ciuleanu TE, Novello S, Ozguroglu M, Goksel T, et al. Aflibercept and docetaxel versus docetaxel alone after platinum failure in patients with advanced or metastatic non-small-cell lung cancer: A randomized, controlled phase III trial. J Clin Oncol 2012;30:3640-7.

[7] Chougule A, Prabhash K, Noronha V, Joshi A, Thavamani A, Chandrani P, et al. Frequency of EGFR mutations in 907 lung adenocarcioma patients of Indian ethnicity. PLoS One 2013;8:e76164.

[8] Kota R, Gundeti S, Gullipalli M, Linga VG, Maddali LS, Digumarti R, et al. Prevalence and outcome of epidermal growth factor receptor mutations in non-squamous non-small cell lung cancer patients. Lung India 2015;32:561-5.

[9] Midha A, Dearden S, McCormack R. EGFR mutation incidence in non-small-cell lung cancer of adenocarcinoma histology: A systematic review and global map by ethnicity (mutMapII). Am J Cancer Res 2015;5:2892-911.

[10] Inoue A, Yoshida K, Morita S, Imamura F, Seto T, Okamoto I, et al. Characteristics and overall survival of EGFR mutation-positive non-small cell lung cancer treated with EGFR tyrosine kinase inhibitors: A retrospective analysis for 1660 Japanese patients. Jpn J Clin Oncol 2016;46:462-7.

[11] Shi Y, Au JS, Thongprasert S, Srinivasan S, Tsai CM, Khoa MT, et al. A prospective, molecular epidemiology study of EGFR mutations in Asian patients with advanced non-small-cell lung cancer of adenocarcinoma histology (PIONEER). J Thorac Oncol 2014;9:154-62.

[12] Choi YL, Sun JM, Cho J, Rampal S, Han J, Parasuraman B, et al. EGFR mutation testing in patients with advanced non-small cell lung cancer: A comprehensive evaluation of real-world practice in an East Asian tertiary hospital. PLoS One 2013;8:e56011.

[13] Choughule A, Noronha V, Joshi A, Desai S, Jambhekar N, Utture S, et al. Epidermal growth factor receptor mutation subtypes and geographical distribution among Indian non-small cell lung cancer patients. Indian J Cancer 2013;50:107-11.

[14] Mehta J. Molecular epidemiology of epidermal growth factor receptor mutations in lung cancers in Indian population. Indian J Cancer 2013;50:102-6.

[15] Greenhalgh J, Dwan K, Boland A, et al. First line treatment of epidermal growth factor receptor (EGFR) mutation positive non-squamous non-small cell lung cancer. Cochrane Database Syst Rev 2016;5:CD010383.

[16] Juan O, Yousaf N, Popat S. First-line epidermal growth factor receptor (EGFR) kinase inhibitors for EGFR mutant non-small cell lung cancer: And the winner is…. Clin Oncol (R Coll Radiol) 2017;29:e1-4.

[17] Sutiman N, Tan SW, Tan EH, Lim WT, Kanesvaran R, Ng QS, et al. EGFR mutation subtypes influence survival outcomes following first-line gefitinib therapy in advanced Asian NSCLC patients. J Thorac Oncol 2017;12:529-38.

[18] Song Z, Zhu H, Guo Z, Wu W, Sun W, Zhang Y, et al. Correlation of EGFR mutation and predominant histologic subtype according to the new lung adenocarcinoma classification in Chinese patients. Med Oncol 2013;30:645.

[19] Villa C, Cagle PT, Johnson M, Patel JD, Yeldandi AV, Raj R, et al. Correlation of EGFR mutation status with predominant histologic subtype of adenocarcinoma according to the new lung adenocarcinoma classification of the international association for the study of lung cancer/American Thoracic Society/European Respiratory Society. Arch Pathol Lab Med 2014;138:1353-7.

[20] Noronha V, Ramaswamy A, Patil VM, Joshi A, Chougule A, Kane S, et al. ALK positive lung cancer: Clinical profile, practice and outcomes in a developing country. PLoS One 2016;11:e0160752.

[21] Shaw AT, Yeap BY, Solomon BJ, Riely GJ, Gainor J, Engelman JA, et al. Effect of crizotinib on overall survival in patients with advanced non-small-cell lung cancer harbouring ALK gene rearrangement: A retrospective analysis. Lancet Oncol 2011;12:1004-12.

[22] Peters S, Camidge DR, Shaw AT, Gadgeel S, Ahn JS, Kim DW, et al. Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer. N Engl J Med 2017;377:829-38.

[23] 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.

Predictive biomarkers in nonsmall cell carcinoma and their clinico-pathological association

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Abstract

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