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Table of Contents
LETTER TO EDITOR
Year : 2020  |  Volume : 3  |  Issue : 2  |  Page : 383-385

Authors' reply to Vora et al. and Singh et al.


1 Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
2 Department of Pathology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
3 Department of Radiodiagnosis, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India

Date of Submission08-Apr-2020
Date of Decision12-Apr-2020
Date of Acceptance20-Apr-2020
Date of Web Publication19-Jun-2020

Correspondence Address:
Vanita Noronha
Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/CRST.CRST_142_20

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How to cite this article:
Kapoor A, Noronha V, Patil VM, Joshi A, Menon N, Chougule A, Chandrani P, Trivedi V, Behel V, Kumar R, Mahajan A, Janu A, Prabhash K. Authors' reply to Vora et al. and Singh et al. Cancer Res Stat Treat 2020;3:383-5

How to cite this URL:
Kapoor A, Noronha V, Patil VM, Joshi A, Menon N, Chougule A, Chandrani P, Trivedi V, Behel V, Kumar R, Mahajan A, Janu A, Prabhash K. Authors' reply to Vora et al. and Singh et al. Cancer Res Stat Treat [serial online] 2020 [cited 2020 Sep 19];3:383-5. Available from: http://www.crstonline.com/text.asp?2020/3/2/383/287208



We thank Vora and Nikita [1] for their interest in our article [2] and the accompanying editorial [3] and providing constructive comments. We performed additional analyses as suggested and report the results in this letter. The survival of patients aged ≤50 years (younger patients) was compared with that of ≥60 years (older patients) by the Kaplan–Meier [4] and Cox regression analysis.[5],[6] The median progression-free survival (PFS) of younger patients (n = 219) was 8.2 months (95% confidence interval [CI], 7.6–8.8) versus 10 months (95% CI, 7.8–12.1) for older patients (n = 199) (P = 0.829). The median overall survival (OS) of younger patients was 23.4 months (95% CI, 18.9–27.8) versus 19.4 months (95% CI, 14.4–24.4) for older patients (Hazard ratio [HR], 1.4; 95% CI, 1.0–1.8, P = 0.034), [Figure 1]. It should be noted that this result is contrary to that reported by Wu et al.[7] in which the shortest median PFS occurred in patients aged ≤50 years (7.3 months), followed by those aged 51–60 years (8.7 months), >80 years (8.8 months), 61–70 years (9.6 months), and 71–80 years (10.1 months) (P = 0.033). Similarly, the study by Kato et al.[8] reported young age to be a predictor of low osimertinib efficacy in both univariate and multivariate analysis in patients with acquired T790M-mutated non-small cell lung cancer patients. The difference in results can be ascribed to the differences in the type of epidermal growth factor receptor (EGFR) mutations in the studies. In the study by Wu et al.,[7] more uncommon EGFR mutations were found in younger patients (22.2% vs. 10.2%; P = 0.009) than in patients aged >50 years. In our study, non-exon 19 EGFR mutations were found in 44% (79/219) of younger patients as compared to 55% (99/199) of older patients (Pearson Chi-square test; P = 0.005). Thus, non-exon 19 EGFR mutation was found to be significantly higher in older patients in our study which might explain the poorer outcomes in older patients.
Figure 1: Kaplan–Meier survival curve of younger (≤50 years) versus older (≥60 years) patients

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We performed a univariate and multivariate analysis by Cox regression method for both PFS and OS in older patients. Smoking status and treatment arm were significantly related to PFS. The patients who received gefitinib had significantly better PFS (HR, 0.3, 95% CI, 0.2–0.6, P < 0.001) as compared to chemotherapy. Similarly, patients receiving gefitinib plus chemotherapy (GC) had better PFS (HR, 0.2, 95% CI, 0.1–0.4, P < 0.001) as compared to chemotherapy alone. When older patients receiving GC were compared with those receiving gefitinib alone, the PFS was significantly better in patients receiving GC (median PFS, 16 months [95% CI, 10.6–21.3] versus 9 months [95% CI, 6.6–11.4]; HR, 1.7; 95% CI, 1.1–2.7, P = 0.012), [Table 1]. The difference in OS was significant in the univariate analysis for gender, smoking status, and the mutation type of EGFR; however, none of them were noted to be significant in the multivariate analysis [Table 2].
Table 1: Univariate and multivariate analysis of progression free survival for older patients (≥60 years)

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Table 2: Univariate and multivariate analysis of overall survival for older patients (≥60 years)

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We thank Singh et al. for their comments and for pointing out the plausible explanation of the effect of smoking on the OS of older patients.[9] In our study, we specifically found that OS in older patients who were smokers was lower than that of younger patients. Cumulatively, more tobacco exposure is expected to occur in older patients as compared to their younger counterparts because of the relatively late diagnosis and smoking cessation. This is in agreement with Wu et al.[7] who reported that current smokers had the shortest PFS (6.9 months) for EGFR-directed therapy when compared with patients who were never-smokers (9.1 months) and ex-smokers (9.4 months) (P = 0.015). Another important issue that has been highlighted by Singh et al.[9] is the impact of drug interactions in older patients with multiple comorbidities. This information was not available in our database, and hence, could not be analyzed. However, it should be noted that we discourage the use of proton-pump inhibitors and H2 blockers in all our patients to avoid the possible interactions.[10] Whenever patients need to take medications for dyspepsia, we advise the use of antacids and ask them to space it from the time of taking tyrosine kinase inhibitors by at least 6 hours.

We would again like to highlight that merely considering numerical age as an exclusion criterion for aggressive treatments should not be the norm and older patients should also be enrolled in future randomized trials so that we can generate more data and can answer more questions with certainty.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Vora AD, Nikita N. Is age just a number for patients with epidermal growth factor receptor-positive lung cancer? Cancer Res Stat Treat 2020;3:380-1.  Back to cited text no. 1
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2.
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. 2
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3.
Friedlaender A, Addeo A. Age is a fact and not an exclusion criterion in EGFR treatment. Cancer Res Stat Treat 2020;3:85-6.  Back to cited text no. 3
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4.
Chakraborty S. A step-wise guide to performing survival analysis. Cancer Res Stat Treat 2018;1:41-5.  Back to cited text no. 4
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5.
Dessai S, Simha V, Patil V. Stepwise cox regression analysis in SPSS. Cancer Res Stat Treat 2018;1:167-70.  Back to cited text no. 5
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Dessai S, Patil V. Testing and interpreting assumptions of COX regression analysis. Cancer Res Stat Treat 2019;2:108-11.  Back to cited text no. 6
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7.
Wu SG, Chang YL, Yu CJ, Yang PC, Shih JY. Lung adenocarcinoma patients of young age have lower EGFR mutation rate and poorer efficacy of EGFR tyrosine kinase inhibitors. ERJ Open Res 2017;3:00092-2016.  Back to cited text no. 7
    
8.
Kato Y, Hosomi Y, Watanabe K, Yomota M, Kawai S, Okuma Y, et al. Impact of clinical features on the efficacy of osimertinib therapy in patients with T790M-positive non-small cell lung cancer and acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors. J Thorac Dis 2019;11:2350-60.  Back to cited text no. 8
    
9.
Singh PK, Chaudhry D, Saxena P. Lung cancer in older patients: Age is not just a number! Cancer Res Stat Treat 2020;3:381-2.  Back to cited text no. 9
    
10.
Rajendra A, Noronha V, Joshi A, Patil VM, Menon N, Prabhash K. Epidermal growth factor receptor-mutated non-small-cell lung cancer: A primer on contemporary management. Cancer Res Stat Treat 2019;2:36-53.  Back to cited text no. 10
  [Full text]  


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