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Table of Contents
EDITORIAL
Year : 2020  |  Volume : 3  |  Issue : 1  |  Page : 85-86

Age is a fact and not an exclusion criterion in EGFR treatment


Department of Oncology, University Hospital of Geneva, Geneva, Switzerland

Date of Submission29-Jan-2020
Date of Decision01-Feb-2020
Date of Acceptance03-Feb-2020
Date of Web Publication24-Feb-2020

Correspondence Address:
Alfredo Addeo
Department of Oncology, University Hospital of Geneva, Rue Perret-Gentil 4, 1205 Geneva
Switzerland
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/CRST.CRST_46_20

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How to cite this article:
Friedlaender A, Addeo A. Age is a fact and not an exclusion criterion in EGFR treatment. Cancer Res Stat Treat 2020;3:85-6

How to cite this URL:
Friedlaender A, Addeo A. Age is a fact and not an exclusion criterion in EGFR treatment. Cancer Res Stat Treat [serial online] 2020 [cited 2020 Apr 4];3:85-6. Available from: http://www.crstonline.com/text.asp?2020/3/1/85/279117



The role and impact of age in and on cancer treatment remains a much-discussed topic. Chronological age often takes second place to biological age, assessed through performance status and comorbidities. In non-small cell lung cancer (NSCLC), it is generally accepted that age is not a limiting factor in itself for choosing to administer chemotherapy, and given the superior outcomes in doublet chemotherapies irrespective of age, European and American guidelines[1],[2] recommend this treatment independently of age. The same trend is observed in immune checkpoint inhibitors and chemo-immunotherapy registration trials: with a median age of 65 years, age appears to impact neither survival nor clinical benefit to these treatments.[3],[4],[5],[6] Similarly, when it comes to targeted therapy, there does not appear to be a difference in efficacy according to age groups.[7],[8]

In the original article entitled 'The efficacy and safety of first line therapy for EGFR mutant NSCLC in older versus younger patients: Pooled analysis of two randomized controlled trials,' in this issue of the journal, the authors have analyzed two Phase III randomized clinical trials assessing the front-line treatment of patients with epidermal growth factor receptor (EGFR)-positive NSCLC.[9] The study aimed to compare survival outcomes and toxicity in older patients with NSCLC harboring EGFR-sensitizing mutations, compared to their younger counterparts. Six hundred and forty patients were included, of which 156 were ≥60 years old.

The analysis revealed a median progression-free survival of 8.5 months (95% confidence interval [CI], 7.8–9.2) in patients under the age of 60 years and 9 months (95% CI, 6.7–11.4) in those over 60 years (hazard ratio [HR], 2.3; 95% CI, 0.8–6.7; P = 0.575). Among younger patients, the median overall survival (OS) was 23.2 months (95% CI, 20.6–25.6), whereas it was 19 months (95% CI, 14.2–23.7) in older patients (HR, 1.18; 95 CI, 0.89–1.54, P = 0.234). In addition, regarding toxicity profiles, there was no difference in Grade 3 or greater adverse events between the two groups, with the exception of an increase in diarrhea among older patients. The most common adverse events were anemia, neutropenia, thrombocytopenia, fatigue, febrile neutropenia, diarrhea, hyponatremia, and rashes.

The definition of older patients is a contentious issue. Varying by country, trial, and pathology, there is no clear consensus on when a patient is considered 'old.' In Western countries and in many large clinical trials, the age of 65–70 years is often used as the cutoff to define older patients. In this article, the authors choose to use 60 years as the cutoff for older patients, justifying their choice by the fact that in India, life expectancy is lower due to socioeconomic and healthcare limitations.

This pooled analysis comprises a heterogeneous treatment group: some patients received first-line gefitinib as monotherapy, whereas others combined chemotherapy with gefitinib. This distinction is important, as there are conflicting data about chemotherapy-induced toxicity among NSCLC patients, as pointed out by the authors in the discussion. Notably, there was no significant difference in treatment-related Grade 3–4 toxicity between older and younger patients.

Furthermore, there was no significant efficacy or survival difference between the entire older cohort and younger group. Upon examination of subgroups, two differences emerged in this analysis. Older males (17.0 vs. 20.9 months, P = 0.033) and smokers (12.1 vs. 19.1 months, P = 0.012) had slightly lower OS compared to their younger counterparts. However, a multivariate analysis was not performed to see if these were independent predictive and prognostic factors. The authors analyze age but also performance status, a known poor prognostic factor in NSCLC, though the data are not mature.[10]

While EGFR-mutant NSCLCs are more often attributed to non-smokers, roughly a third of the patients in this analysis have a smoking history. Tobacco is a known predictor of resistance to EGFR-targeted therapy and a poor prognostic factor.[11] Predominantly among older patients, tobacco use is also strongly correlated with cardiovascular and pulmonary diseases, with a major impact on cancer-independent survival. As tobacco use is more prevalent among men in India, the decreased survival of older men could be attributed to both cancer-related and cancer-independent factors.

The authors conclude that the treatment of EGFR-mutant NSCLC patients should not be hindered by age, given similar survival and toxicity results among patients older or younger than 60 years of age. In a pooled analysis, a multivariate analysis would complement the results and help to potentially understand which patients may not derive as much benefit from these treatments. However, given the nature of the analysis, this should be regarded as exploratory and not practice changing. Moreover, the group of patients receiving chemotherapy and gefitinib likely represents a selected population in terms of fitness and comorbidities, and we would be cautious about applying this treatment to a general older population based on this analysis.

It is rather reassuring that single-agent targeted therapy in this patient population mirrors the results already seen and well known from larger, multicentric randomized trials.[7],[12],[13] As expected, age on its own should not be a decisive therapeutic factor for these patients and more precise tools should be adopted to assess patient fitness.



 
  References Top

1.
National Comprehensive Cancer Network. NSCLC (Version 3.2019). Available from: https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. [Last accessed on 2020 Jan 28].  Back to cited text no. 1
    
2.
Planchard D, Popat S, Kerr K, Novello S, Smit EF, Faivre-Finn C, et al. Metastatic non-small cell lung cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 2018;29:iv192-237.  Back to cited text no. 2
    
3.
Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, et al. Updated analysis of KEYNOTE-024: Pembrolizumab versus platinum-based chemotherapy for advanced non-small-cell lung cancer with PD-L1 Tumor proportion score of 50% or Greater. J Clin Oncol 2019;37:537-46.  Back to cited text no. 3
    
4.
Gandhi L, Rodríguez-Abreu D, Gadgeel S, Esteban E, Felip E, De Angelis F, et al. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med 2018;378:2078-92.  Back to cited text no. 4
    
5.
Paz-Ares L, Luft A, Vicente D, Tafreshi A, Gümüş M, Mazières J, et al. Pembrolizumab plus chemotherapy for squamous non-small-cell lung cancer. N Engl J Med 2018;379:2040-51.  Back to cited text no. 5
    
6.
Addeo A, Banna GL, Metro G, Di Maio M. Chemotherapy in combination with immune checkpoint inhibitors for the first-line treatment of patients with advanced non-small cell lung cancer: A systematic review and literature-based meta-analysis. Front Oncol 2019;9:264.  Back to cited text no. 6
    
7.
Ramalingam SS, Vansteenkiste J, Planchard D, Cho BC, Gray JE, Ohe Y, et al. Overall survival with osimertinib in untreated, EGFR-mutated advanced NSCLC. N Engl J Med 2020;382:41-50.  Back to cited text no. 7
    
8.
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.  Back to cited text no. 8
    
9.
Kapoor A, Noronha V, Patil VM, Joshi A, Menon N, Chougule A, et al. The efficacy and safety of first-line therapy for the epidermal growth factor receptor mutant non-small-cell lung cancer in older versus younger patients: A pooled analysis of two randomized controlled trials. Cancer Res Stat Treat 2020;3:44-50.  Back to cited text no. 9
  [Full text]  
10.
Friedlaender A, Banna GL, Buffoni L, Addeo A. Poor-performance status assessment of patients with non-small cell lung cancer remains vague and blurred in the immunotherapy era. Curr Oncol Rep 2019;21:107.  Back to cited text no. 10
    
11.
Kim IA, Lee JS, Kim HJ, Kim WS, Lee KY. Cumulative smoking dose affects the clinical outcomes of EGFR-mutated lung adenocarcinoma patients treated with EGFR-TKIs: A retrospective study. BMC Cancer 2018;18:768.  Back to cited text no. 11
    
12.
Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, 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;12:735-42.  Back to cited text no. 12
    
13.
Park K, Tan EH, O'Byrne K, Zhang L, Boyer M, Mok T, et al. Afatinib versus gefitinib as first-line treatment of patients with EGFR mutation-positive non-small-cell lung cancer (LUX-Lung 7): A phase 2B, open-label, randomised controlled trial. Lancet Oncol 2016;17:577-89.  Back to cited text no. 13
    




 

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