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LCC-A SYMPOSIUM-EDITORIAL
Year : 2013  |  Volume : 50  |  Issue : 2  |  Page : 77-79
 

Personalized medicine: Lung Cancer leads the way


Lung Cancer Consortium - Asia

Date of Web Publication27-Aug-2013

Correspondence Address:
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-509X.117005

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How to cite this article:
Parikh P, Puri T. Personalized medicine: Lung Cancer leads the way. Indian J Cancer 2013;50:77-9

How to cite this URL:
Parikh P, Puri T. Personalized medicine: Lung Cancer leads the way. Indian J Cancer [serial online] 2013 [cited 2019 Oct 13];50:77-9. Available from: http://www.indianjcancer.com/text.asp?2013/50/2/77/117005


Management of lung cancer has undergone a dramatic transformation over the last few years. [1] It can easily be said that non-small-cell lung cancer (NSCLC) is the poster boy of successful personalized medicine. Today, it would be unthinkable to treat such a patient without knowing the molecular signature of the tumor, and these changes have percolated to all stakeholders in its management-medical oncologists, pathologists, regulatory authorities, and patient advocacy groups. The minisymposium by the Lung Cancer Consortium: Asia on the molecular biology of lung cancer in this issue of the Indian Journal of Cancer (IJC) is proof to support this, with collective data of more than 2,500 patients with NSCLC. [2],[3],[4],[5],[6]

Lung cancer is the commonest malignancy globally as well as in India. [7] Its mortality is also very high. In India as well as other south Asian countries, its diagnosis is compounded by the high incidence of pulmonary tuberculosis. [8] Hence, the strategy for early and accurate diagnosis is of vital importance. Pathologists are now aware that clinicians will not accept a report without subclassification of the type of NSCLC, and radiologists ensure that imaging-guided biopsy/cytology is done with accuracy so as not to have to repeat it. [9]

What is it that has driven this transformation? It is the knowledge that survival even in stage IV NSCLC can now be doubled with excellent quality of life if patients are treated with oral therapy when this is selected appropriately. [1],[7],[9],[10],[11],[12] Epidermal growth factor receptor (EGFR) mutation testing is the classical example. [9],[13] Availability of the first report about the incidence of EGFR mutation in 220 patients with NSCLC from India indicated it to be as high as 51.8%. [14] Speculation of its true incidence have been rampant since then. [15],[16] We now have data from more than 1,500 patients. [Table 1] summarizes this information collected over the last four years and [Figure 1] compares that with the data from other countries of the world. [2],[3],[4],[5],[6]
Figure 1: Incidence of EGFR mutation in NSCLC: Geographical distribution

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Table 1: Pattern of EGFR mutations in Indian patients with NSCLC

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The take-home messages from this minisymposium are as follows:

The consequences of identifying EGFR mutation reflect in the first real documentation of pharmcogenomic differences in oncology. [17] The real incidence of EGFR mutation in patients with NSCLC is between 25 and 40%. It will be higher if samples are from patients with adenocarcinoma alone and lower if all patients with lung cancer are included. Similarly, the incidence will be higher if next-generation sequencing (NGS) technology is used and lower if only known mutations are identified using a limited number of polymerase chain reaction (PCR) primers.

The type and quality of the tumor sample plays an important role. Studies using formalin-fixed paraffin blocks tend to have a lower incidence of EGFR mutations and a higher number of samples that fail to give results. Hence, attention to the technique used and quality assurance are vital while interpreting the data and making decisions about clinical treatment. In the near future, we envisage an increasing demand for various tests on the cytology/biopsy specimen. Hence, we will need to come up with SOPs to ensure their optimal utilization.

The incidence of EGFR mutations is higher in women, nonsmokers, and patients with adenocarcinoma histology. This so-called 'gospel truth' needs to be taken with a pinch of salt. Though the 220 patients reported by Sahoo et al. showed 44, 53, and 83% prevalence of these subgroups, respectively, among Indian patients, the systematic review of 4,700 patients reported by Behera and Balamugeshshowed the same subgroups to represent 17, 15, and 26% of their patients. [14],[18] Comparing data from before 2004 to that published in 2011 is like comparing apples with oranges. A lot has changed in the interim, including the histology and smoking pattern. [19] In this issue of IJC, Choghule et al. have showed in a large cohort (N = 1018) that EGFR mutations in NSCLC were seen in 34% of females, 21% of males, 32% of never smokers, and 16% of smokers. [6] On the other hand, whether EGFR mutations increase with other features like age, metastasis, or progression of disease remains unclear at this time. Even more surprisingly, the incidence of these mutations among males with adenocarcinoma (35%) matches that among the fairer gender having the same histology (36%). [6] Hence, no patient should be denied treatment with tyrosine-kinase inhibitors (TKIs) on the basis of clinical features alone.

Patients can have more than one mutation, a feature often missed in most publications. As specific mutations are linked to TKI resistance, this factor must be kept in mind; else, be ready to be surprised when your patient fails to respond as expected.

It is not an uncommon situation where the patient is commenced on standard platinum doublet chemotherapy before the result of the EGFR testing becomes available. What if such a patient is found to have a mutation? Data from Bhat et al. would indicate that it is better for such patients to complete the chemotherapy and then use switch maintenance with oral TKIs. [3] The median progression-free survival (PFS) in these patients seems to be significantly higher [14 months; 95% confidence interval (CI) of 12-16 months] as compared to the group appropriately commenced on TKI upfront (8 months; 95% CI of 7-8 months). As EGFR mutation also predicts better response to chemotherapy, it remains to be seen whether this is the result of switch maintenance alone.

Finally, the anaplastic lymphoma kinase (ALK) mutation is a very interesting story, especially as treatment in such patients can more than double the survival with a form of therapy that leads to dramatic improvement in quality of life. Access to crizotinib would almost make one hope that the patient with advanced NSCLC has a wild-type EGFR and falls into the minority (2.7%) with ALK mutation. [5]

 
  References Top

1.Parikh P, Chang AY, Nag S, Digumarti R, Bhattacharyya GS, Doval DC, et al. Clinical experience with gefitinib in Indian patients. J Thorac Oncol 2008;3:380-5.  Back to cited text no. 1
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2.Veldore VH, Rao RM, Kakare S, Pattanayak S, Tejaswi R, Sahoo R, et al. EGFR mutation in NSCLC: A retrospective analysis of 1036 lung cancer specimens from a network of tertiary cancer care centers in India. Indian J Cancer 2013.  Back to cited text no. 2
    
3.Bhat AD, Pai R, Rebekah R, Nehru GA, Dhananjayan S, Abraham S, et al. Clinicopathological features of non-small cell lung cancer in India and correlation with epidermal growth factor receptor [egfr] mutational status. Indian J Cancer 2013.  Back to cited text no. 3
    
4.Mehta J. Molecular epidemiology of epidermal growth factor receptor mutations in lung cancers in Indian population. Indian J Cancer 2013.  Back to cited text no. 4
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5.Desai SS, Shah A, Prabhash K, Jambhekar NA. A year of anaplastic large cell kinase testing for lung carcinoma: Pathological and technical perspectives. Indian J Cancer 2013.  Back to cited text no. 5
    
6.Choughule A, Noronha V, Joshi A, Dutt A, Desai S, Utture S, et al. EGFR mutation and its subtypes in Indian population: A study from single academic centre. Indian J Cancer 2013.  Back to cited text no. 6
    
7.Prasad N, Bakshi A, Deshmukh C, Hingmire S, Ranade AA, Parikh P. Importance of dose intensity in treatment of advanced non-small cell lung cancer in the elderly. South Asian J Cancer, 2012;1:9-15.  Back to cited text no. 7
    
8.Bhatt ML, Kant S, Bhaskar R. Pulmonary tuberculosis as differential diagnosis of lung cancer. South Asian J Cancer 2012;1:36-42.  Back to cited text no. 8
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9.Hirsch FR, Varella-Garcia M, Bunn PA Jr, Franklin WA, Dziadziuszko R, Thatcher N, et al. Molecular predictors of outcome with gefitinib in a phase III placebo-controlled study in advanced non-small-cell lung cancer. J Clin Oncol 2006;24:5034-42.  Back to cited text no. 9
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10.Parikh PM. Treatment of Lung Cancer in the Elderly. Ind J Med and Pead Oncol 1999;2:140-7.  Back to cited text no. 10
    
11.Parikh PM, Vaid A, Advani SH, Digumarti R, Madhavan J, Nag S, et al. Randomized, double-blind, placebo-controlled phase ii study of single-agent oral talactoferrin in patients with locally advanced or metastatic non-small-cell lung cancer that progressed after chemotherapy. J Clin Oncol 2011;29:4129-36.  Back to cited text no. 11
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12.Louis RA, Rajendranath R, Ganesan P, Sagar TG, Krishnamurthy A. First report of upfront treatment with Gefitinib in comparison with chemotherapy in advanced non-small cell lung cancer patients from south India: Analysis of 120 patients. Indian J Med Paediatr Oncol. 2012;33:146-54.  Back to cited text no. 12
    
13.Chang A, Parikh P, Thongprasert S, Tan EH, Perng RP, Ganzon D, et al. Gefitinib (IRESSA) in patients of Asian origin with refactory advanced non-small-cell lung cancer: Subset analysis from the ISEL study. J Thorac Oncol 2006;1:847-55.  Back to cited text no. 13
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14.Sahoo R, Harini VV, Babu VC, Patil Okaly GV, Rao S, Nargund A, et al. Screening for EGFR mutations in lung cancer, a report from India. Lung Cancer. 2011;73:316-9.  Back to cited text no. 14
    
15.Jiwnani S, Karimundackal G, Pramesh CS, Prabhash K. What is the true prevalence of EGFR mutations in India? Lung Cancer 2011;74:549.  Back to cited text no. 15
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16.Noronha V, Prabhash K, Thavamani A, Chougule A, Purandare N, Joshi A, et al. EGFR mutations in Indian lung cancer patients: Clinical correlation and outcome to EGFR targeted therapy. PLoS One 2013;8:e61561.  Back to cited text no. 16
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17.Thatcher N, Chang A, Parikh P, Rodrigues Pereira J, Ciuleanu T, von Pawel J, et al. Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: Results from a randomised, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer). Lancet 2005;366:1527-37.  Back to cited text no. 17
[PUBMED]    
18.Behera D Balamugesh T. Lung cancer in India. Indian J Chest Dis Allied Sci 2004;46:269-81.  Back to cited text no. 18
    
19.Noronha V, Dikshit R, Raut N, Joshi A, Pramesh CS, George K, et al. Epidemiology of lung cancer in India: Focus on the differences between non-smokers and smokers: A single-centre experience. Indian J Cancer 2012;49:74-81.  Back to cited text no. 19
[PUBMED]  Medknow Journal  


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