Prevalence of highly actionable mutations among Indian patients with advanced non-small cell lung cancer: A systematic review and meta-analysis
Ruchir Raman
Centre of Excellence for Biopharmaceutical Technology, Indian Institute of Technology, Delhi, India
Department of Chemical Engineering, Indian Institute of Technology, Delhi, India
Search for more papers by this authorVarun Ramamohan
Department of Mechanical Engineering, Indian Institute of Technology, Delhi, India
Search for more papers by this authorAnurag Rathore
Centre of Excellence for Biopharmaceutical Technology, Indian Institute of Technology, Delhi, India
Department of Chemical Engineering, Indian Institute of Technology, Delhi, India
Search for more papers by this authorDeepali Jain
Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
Search for more papers by this authorAnant Mohan
Department of Pulmonary, Critical Care and Sleep Medicine, All Indian Institute of Medical Sciences, New Delhi, India
Search for more papers by this authorCorresponding Author
Vishal Vashistha
Department of Pulmonary, Critical Care and Sleep Medicine, All Indian Institute of Medical Sciences, New Delhi, India
Section of Hematology and Oncology, Department of Medicine, New Mexico Veterans Affairs Medical Center, Albuquerque, New Mexico, USA
University of New Mexico Cancer Center, Albuquerque, New Mexico, USA
Correspondence
Vishal Vashistha, Section of Hematology and Oncology, Department of Medicine, New Mexico Veterans Affairs Medical Center, Albuquerque, NM, USA 87109.
Email: [email protected]
Search for more papers by this authorRuchir Raman
Centre of Excellence for Biopharmaceutical Technology, Indian Institute of Technology, Delhi, India
Department of Chemical Engineering, Indian Institute of Technology, Delhi, India
Search for more papers by this authorVarun Ramamohan
Department of Mechanical Engineering, Indian Institute of Technology, Delhi, India
Search for more papers by this authorAnurag Rathore
Centre of Excellence for Biopharmaceutical Technology, Indian Institute of Technology, Delhi, India
Department of Chemical Engineering, Indian Institute of Technology, Delhi, India
Search for more papers by this authorDeepali Jain
Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
Search for more papers by this authorAnant Mohan
Department of Pulmonary, Critical Care and Sleep Medicine, All Indian Institute of Medical Sciences, New Delhi, India
Search for more papers by this authorCorresponding Author
Vishal Vashistha
Department of Pulmonary, Critical Care and Sleep Medicine, All Indian Institute of Medical Sciences, New Delhi, India
Section of Hematology and Oncology, Department of Medicine, New Mexico Veterans Affairs Medical Center, Albuquerque, New Mexico, USA
University of New Mexico Cancer Center, Albuquerque, New Mexico, USA
Correspondence
Vishal Vashistha, Section of Hematology and Oncology, Department of Medicine, New Mexico Veterans Affairs Medical Center, Albuquerque, NM, USA 87109.
Email: [email protected]
Search for more papers by this authorAbstract
Background
Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality in India. To clarify rates of actionable mutations, and thereby identify opportunities to improve the delivery of best available care for a large volume of patients, a comprehensive review of available data is warranted.
Methods
Studies that reported prevalence of any actionable gene variant among adult Indian patients with advanced NSCLC were selected from three databases (PubMed, EMBASE, and Cochrane Library). Ranges in actionable variant prevalence were reported. Meta-analysis of proportions was completed among studies specifically evaluating mutational prevalence within ALK or EGFR. Sensitivity analyses were undertaken among populations sharing high heterogeneity.
Results
Twenty-six studies were selected. Ranges in actionable mutational prevalence among NSCLC patients were as follows: ALK: 4.1–21.4%, BRAF: 1.5–3.5%, EGFR: 11.9–51.8%, HER2: 0–1.5%, KRAS: 4.5–6.4%, NTRK: 0–.7%, and ROS-1: 3.5–4.1%. Following sensitivity analysis, pooled ALK mutational prevalence rates were 8.3% (95% CIs: 6.6–10.4%) and 4.01% (95% CIs: 2.3–7.0) for adenocarcinoma and NSCLC patients, respectively. Pooled EGFR mutational prevalence rates were 28.7% (95% CIs: 23.5–34.6%) and 24.2% (95% CIs: 19.9–29.1%) for adenocarcinoma and NSCLC patients, respectively.
Conclusions
Nearly 40% of Indian patients with advanced adenocarcinoma and 30% with NSCLC share an actionable mutation in ALK or EGFR. Approximately one-half of adenocarcinoma patients have an actionable variant. Efforts should be directed toward efficiently identifying candidates for targeted agents and delivering such treatments.
Open Research
DATA AVAILABILITY STATEMENT
Data sharing is not applicable to this article as no new data were created or analyzed in this study.
Supporting Information
| Filename | Description |
|---|---|
| ajco13802-sup-0001-SupMat.docx19 KB | Table S1. Prevalence rates among nonsensitizing EGFR mutations |
| ajco13802-sup-0002-SupMat.docx17.4 KB | Table S2. Study mutation rates (pooled prevalence for detection of mutations over time) |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
REFERENCES
- 1Sung H, Ferlay J, Siegel R, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021; 71(3): 209-249.
- 2Ferlay J, Ervik M, Lam F, et al. Global Cancer Observatory: Cancer Today. International Agency for Research on Cancer; 2020.
- 3Bareschino MA, Schettino C, Rossi A, et al. Treatment of advanced non small cell lung cancer. J Thoracic Dis. 2011; 3(2): 122-133.
- 4Vashistha V, Garg A, Iyer H, et al. Treatment patterns among lower-income Indian patients with metastatic non-small cell lung cancer harboring EGFR mutations or ALK rearrangements. Chest. 2020; 158(4):A1869.
- 5Politii K, Herbst RS. Lung cancer in the era of precision medicine. Clin Cancer Res. 2015; 21(10): 2213-2220.
- 6Yuan M, Huang LL, Chen JH, et al. The emerging treatment landscape of targeted therapy in non-small-cell lung cancer. Sig Transduct Target Ther. 2019; 4(1):61.
- 7Mitsudomi T. Molecular epidemiology of lung cancer and geographic variations with special reference to EGFR mutations. Transl Lung Cancer Res. 2014; 3(4): 205-211.
- 8Dearden S, Stevens J, Wu YL, Blowers D. Mutation incidence and coincidence in non small-cell lung cancer: meta-analyses by ethnicity and histology (mutMap). Ann Oncol. 2013; 24(9): 2371-2376.
- 9Graham RP, Treece AL, Lindeman NI, et al. Worldwide frequency of commonly detected EGFR mutations. Arch Pathol Lab Med. 2018; 142(2): 163-167.
- 10Solomon B, Varella-Garcia M, Camidge D. 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.
- 11Barendregt J, Doi S, Lee Y, et al. Meta-analysis of prevalence. J Epidemiol Community Health. 2013; 67(11): 974-978.
- 12Higgins J, Thompson S, Deeks J, Altman D. Measuring inconsistency in meta-analyses. BMJ. 2003; 327(7414): 557-560.
- 13Bal A, Singh N, Agarwal P, et al. ALK gene rearranged lung adenocarcinomas: molecular genetics and morphology in cohort of patients from North India. APMIS. 2016; 124(10): 832-838.
- 14Bharadwaj R, Dewan K, Mann N. Genetic analysis of EGFR mutations in non-small cell lung carcinoma: a tertiary care center experience. J Med Soc. 2016; 30(1): 44.
10.4103/0972-4958.175851 Google Scholar
- 15Bhatt V, D'Souza S, Smith L, et al. Epidermal growth factor receptor mutational status and brain metastases in non–small-cell lung cancer. J Glob Oncol. 2016; 3(3): 208-217.
- 16Bhaumik S, Ahmad F, Das B. Somatic mutation analysis of KRAS, BRAF, HER2 and PTEN in EGFR mutation-negative non-small cell lung carcinoma: determination of frequency, distribution pattern and identification of novel deletion in HER2 gene from Indian patients. Med Oncol. 2016; 33(10): 1-11.
- 17Chatterjee K, Bhoumik R, Chattopadhyay B. Regional reporting of the incidence of anaplastic lymphoma kinase mutation in 379 non-small-cell lung cancer patients from Kolkata: using immunohistochemistry as the diagnostic modality in a significant subset. South Asian J Cancer. 2017; 6: 169-170.
- 18Choughule A, Noronha V, Joshi A, et al. Epidermal growth factor receptor mutation subtypes and geographical distribution among Indian non-small cell lung cancer patients. Indian J Cancer. 2013; 50(2): 107-111.
- 19Das B, Bhaumik S, Ahmad F, et al. Molecular spectrum of somatic EGFR and KRAS gene mutations in non small cell lung carcinoma: determination of frequency, distribution pattern and identification of novel variations in Indian patients. Pathol Oncol Res. 2015; 21(3): 675-687.
- 20Dattatreya S, Bansal R, Vamsy M, et al. Clinicopathological profile of lung cancer at a tertiary care center. Indian J Cancer. 2018; 55(1): 273-275.
- 21Doval D, Azam S, Batra U, et al. Epidermal growth factor receptor mutation in lung adenocarcinoma in India: a single center study. J Carcinog. 2013; 12(1): 12.
- 22Doval D, Sinha R, Batra U, et al. Clinical profile of nonsmall cell lung carcinoma patients treated in a single unit at a tertiary cancer care center. Indian J Cancer. 2017; 54(1): 193-196.
- 23Dubey A, Pathi N, Viswanath S, et al. New insights into anaplastic lymphoma kinase-positive nonsmall cell lung cancer. Indian J Cancer. 2017; 54(1): 203-208.
- 24Govindarajan S, Adiga D, Lobo F, et al. Advanced stage lung cancer: persisting challenges in the era of molecular targeted therapy—our experience. J Clin Diagnostic Res. 2018; 12(5): EC14-EC17.
- 25Gupta P, Gowrishankar S, Swain M. Epidermal growth factor receptor and anaplastic lymphoma kinase mutation in adenocarcinoma lung: their incidence and correlation with histologic patterns. Indian J Pathol Microbiol. 2019; 62(1): 24-30.
- 26Joshi A, Pande N, Noronha V, et al. ROS1 mutation non-small cell lung cancer—access to optimal treatment and outcomes. Ecancermedicalscience. 2019; 13: 1-9.
- 27Kasana B, Dar W, Aziz S, et al. Epidermal growth factor receptor mutation in adenocarcinoma lung in a North Indian population: prevalence and relation with different clinical variables. Indian J Med Paediatr Oncol. 2016; 37(3): 189-195.
- 28Kota R, Gundeti S, Gullipalli M, et al. Prevalence and outcome of epidermal growth factor receptor mutations in non-squamous non-small cell lung cancer patients. Lung India. 2015; 32(6): 561-565.
- 29Mehta J. Molecular epidemiology of epidermal growth factor receptor mutations in lung cancers in Indian population. Indian J Cancer. 2013; 50(2): 102-106.
- 30Mehta A, Nathany S, Tripathi R, et al. Non-amplification genetic alterations of HER2 gene in non-small cell lung carcinoma. J Clin Pathol. 2021; 74(2): 106-110.
- 31Mohan A, Garg A, Gupta A, et al. Clinical profile of lung cancer in North India: a 10 year analysis of 1862 patients from a tertiary care center. Lung India. 2020; 37(3): 190-197.
- 32Murthy S, Rajappa S, Gundimeda S, et al. Anaplastic lymphoma kinase status in lung cancers: an immunohistochemistry and fluorescence in situ hybridization study from a tertiary cancer center in India. Indian J Cancer. 2017; 54(1): 231-235.
- 33Rana V, Ranjan P, Jagani R, et al. A study of therapy targeted EGFR/ALK mutations in Indian patients with lung adenocarcinoma: a clinical and epidemiological study. Med J Armed Forces India. 2018; 74(2): 148-153.
- 34Sahoo R, Harini VV, Babu VC, et al. Screening for EGFR mutations in lung cancer, a report from India. Lung Cancer. 2011; 73(3): 316-319.
- 35Shankar S, Thanasekaran V, Dhanasekar T, et al. Clinicopathological and immunohistochemical profile of non-small cell lung carcinoma in a tertiary care medical centre in South India. Lung India. 2014; 31(1): 23-28.
- 36Shi Y, Au J, Thongprasert S, 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(2): 154-162.
- 37Shukla S, Pandey R, Kant S, et al. Detection of anaplastic lymphoma kinase gene re-arrangement in non-small cell lung carcinoma in the Indian population: comparison of techniques and immunohistochemistry clones. Turk Patoloji Derg. 2019; 35(1): 36-45.
- 38Singh R, Rohtagi N. Clinicopathological and molecular epidemiological study of lung cancer patients seen at a tertiary care hospital in Northern India. South Asian J Cancer. 2017; 6(4): 171-175.
- 39Midha 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(9): 2892-2911.
- 40Fan L, Feng Y, Wan H, et al. Clinicopathological and demographical characteristics of non-small cell lung cancer patients with ALK rearrangements: a systematic review and meta-analysis. PLoS One. 2014; 9(6):e100866.
- 41Rosell R, Carcereny E, Gervais R, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012; 13(3): 239-246.
- 42Zhou C, Wu Y, Chen G, et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 2011; 12(8): 735-742.
- 43Mitsudomi T, Morita S, Yatabe Y, et al. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol. 2010; 11(2): 121-128.
- 44Maemondo M, Inoue A, Kobayashi K, et al. Gefitinib or chemotherapy for non–small-cell lung cancer with mutated EGFR. N Engl J Med. 2010; 362(25): 2380-2388.
- 45Sequist L, Yang J, Yamamoto N, et al. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013; 31(27): 3327-3334.
- 46Soria J, Ohe Y, Vansteenkiste J, et al. Osimertinib in untreated EGFR-mutated advanced non–small-cell lung cancer. N Engl J Med. 2018; 378(2): 113-125.
- 47Soria J, Tan D, 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.
- 48Solomon B, Mok T, Kim D, et al. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med. 2014; 371(23): 2167-2177.
- 49Mok T, Camidge D, Gadgeel S, et al. Updated overall survival and final progression-free survival data for patients with treatment-naive advanced ALK-positive non-small-cell lung cancer in the ALEX study. Ann Oncol. 2020; 31(8): 1056-1064.
- 50Camidge D, Kim H, Ahn M, et al. Brigatinib versus crizotinib in advanced ALK inhibitor–naive ALK-positive non–small cell lung cancer: second interim analysis of the phase III ALTA-1L trial. J Clin Oncol. 2020; 38(31): 3592-3603.
- 51Baldacci S, Besse B, Avrillon V, et al. 1303P Lorlatinib for advanced ALK+ non-small cell lung cancer (NSCLC): efficacy and safety data from IFCT-1803 LORLATU expanded access program (EAP) cohort. Ann Oncol. 2020; 31: S843.
- 52Wu Y, Yang J, Kim D, et al. Phase II study of crizotinib in East Asian patients with ROS1-positive advanced non–small-cell lung cancer. J Clin Oncol. 2018; 36(14): 1405-1411.
- 53Shaw A, Riely G, Bang Y, et al. Crizotinib in ROS1-rearranged advanced non-small-cell lung cancer (NSCLC): updated results, including overall survival, from PROFILE 1001. Ann Oncol. 2019; 30(7): 1121-1126.
- 54Drilon A, Siena S, Dziadziuszko R, et al. Entrectinib in ROS1 fusion-positive non-small-cell lung cancer: integrated analysis of three phase 1–2 trials. Lancet Oncol. 2020; 21(2): 261-270.
- 55Planchard D, Smit E, Groen H, et al. Dabrafenib plus trametinib in patients with previously untreated BRAF V600E-mutant metastatic non-small-cell lung cancer: an open-label, phase 2 trial. Lancet Oncol. 2017; 18(10): 1307-1316.
- 56Mazieres J, Cropet C, Montané L, et al. Vemurafenib in non-small-cell lung cancer patients with BRAF V600 and BRAF non V600 mutations. Ann Oncol. 2020; 31(2): 289-294.
- 57Hong D, DuBois S, Kummar S, et al. Larotrectinib in patients with TRK fusion-positive solid tumours: a pooled analysis of three phase 1/2 clinical trials. Lancet Oncol. 2020; 21(4): 531-540.
- 58Doebele R, Drilon A, Paz-Ares L, et al. Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: integrated analysis of three phase 1–2 trials. Lancet Oncol. 2020; 21(2): 271-282.
- 59Drilon A, Oxnard G, Tan D, et al. Efficacy of selpercatinib in RET fusion–positive non–small-cell lung cancer. N Engl J Med. 2020; 383(9): 813-824.
- 60Wolf J, Seto T, Han J, et al. Capmatinib in MET exon 14–mutated or MET-amplified non–small-cell lung cancer. N Engl J Med. 2020; 383(10): 944-957.
- 61Caduff C, Booth C, Pramesh C, et al. India's new health scheme: what does it mean for cancer care? Lancet Oncol. 2019; 20(6): 757-758.
- 62Lee C, Kim S, Lee JS, et al. Next-generation sequencing reveals novel resistance mechanisms and molecular heterogeneity in EGFR-mutant non-small cell lung cancer with acquired resistance to EGFR-TKIs. Lung Cancer. 2017; 113: 106-114.
- 63Jing C, Mao X, Wang Z, et al. Next-generation sequencing-based detection of EGFR, KRAS, BRAF, NRAS, PIK3CA, Her-2 and TP53 mutations in patients with non-small cell lung cancer. Mol Med Rep. 2018; 18(2): 2191-2197.
- 64Letovanec I, Finn S, Zygoura P, et al. Evaluation of NGS and RT-PCR methods for ALK rearrangement in European NSCLC patients: results from the European Thoracic Oncology Platform Lungscape Project. J Thorac Oncol. 2018; 13(3): 413-425.
- 65Wang X, Kattan M. Cohort studies: design, analysis and reporting. Chest. 2020; 158(1): S72-S78.
