Efficacy of Second-Line Pemetrexed-Carboplatin in EGFR-Activating Mutation-Positive NSCLC: Does Exon 19 Deletion Differ from Exon 21 Mutation?

Amit Joshi,Anuradha Chougule,Nikhil Pande,Kumar Prabhash,Vanita Noronha,Alok Goel,Atanu Bhattacharjee,Supriya Goud,Vikas Talreja,Ashay Karpe,Sucheta More,Abhishek Mahajan,Nilendu Purandare,Amit Janu,Arun Chandrasekharan,Anant Ramaswamy,Rajiv Kumar ,Vijay Patil

doi:10.1155/2017/8196434

Abstract

Background It is unknown whether the outcomes of second-line pemetrexed-carboplatin chemotherapy administered after progression on gefitinib are dependent on type of EGFR mutation present at baseline. Method Adult non-small-cell lung cancer patients, with exon 19 deletion or exon 21 L858R mutation, who progressed on gefitinib and received pemetrexed-carboplatin chemotherapy were selected for this analysis. Result 55 patients received pemetrexed-carboplatin as second-line treatment. Response rates in evaluable patients were 39.3% in exon 19 patients (n = 28) and 33.3% in exon 21 patients (n = 15) (p = 0.752, Fisher's exact 2-sided p value). The median PFS in exon 19 and 21 cohorts was 5.900 months (95% CI: 4.274–7.526) and 4.767 months (95% CI: 1.374–8.159), respectively. The median overall survival in exon 19 patients was (11.8 months, 95% CI: 9.916–13.684 months) significantly better than that seen in exon 21 mutation patients (6.2 months, 95% CI: 4.215–8.118 months, p = 0.024) on univariate analysis; however, on multivariate analysis, this association was not confirmed (HR = 0.361, 95% CI: 0.090–1.439, p = 0.149). Conclusion Exon 19 deletion has no impact on PFS and OS in EGFR-mutated patients treated with second-line pemetrexed-carboplatin.

Highlights

The treatment of EGFR exon 19-deleted and exon 21 L858Rsubstituted non-small-cell lung cancer (NSCLC) is through tyrosine kinase inhibitor (TKI) [1]
The response rates, progression-free survival (PFS), and overall survival (OS) of exon 19 deletion patients treated with TKI are significantly better than those of exon 21 mutation patients
Adult NSCLC patients, with exon 19 deletion or exon 21 L858R mutation, who progressed on gefitinib and received pemetrexed-platinum chemotherapy were selected for this analysis

Summary

Introduction

The treatment of EGFR exon 19-deleted and exon 21 L858Rsubstituted non-small-cell lung cancer (NSCLC) is through tyrosine kinase inhibitor (TKI) [1]. Reversible and irreversible tyrosine kinase inhibitors have proven their worth against platinum doublet chemotherapy agents in multiple studies [2,3,4] In majority of these studies done across the globe, TKIs lead to an improvement in treatment-related outcomes. The response rates, progression-free survival (PFS), and overall survival (OS) of exon 19 deletion patients treated with TKI are significantly better than those of exon 21 mutation patients. These classic EGFR-activating mutated patients at progression are treated with platinum doublet chemotherapy. Adult non-small-cell lung cancer patients, with exon 19 deletion or exon 21 L858R mutation, who progressed on gefitinib and received pemetrexed-carboplatin chemotherapy were selected for this analysis. Exon 19 deletion has no impact on PFS and OS in EGFR-mutated patients treated with second-line pemetrexedcarboplatin

Methods

Results

Conclusion