ecancermedicalscience

Clinical Study

Impact of exon 19 versus exon 21 EGFR-activating mutation on outcomes with upfront pemetrexed–carboplatin chemotherapy

24 Oct 2017
Vanita Noronha, Vijay Patil, Amit Joshi, Anuradha Chougule, Atanu Bhattacharjee, Rajiv Kumar, Sucheta More, Supriya Goud, Ashay Karpe, Anant Ramaswamy, Nikhil Pande, Arun Chandrasekharan, Alok Goel, Vikas Talreja, Abhishek Mahajan, Amit Janu, Nilendu Purandare, Kumar Prabhash

Background: EGFR mutation subtype is a recognised factor impacting outcomes of patients receiving oral tyrosine kinase inhibitors (TKIs) in non-small-cell lung cancer (NSCLC). Evidence for the effect of this factor on outcomes in patients receiving pemetrexed is limited.

Methods: We completed a study comparing pemetrexed–platinum combination versus oral TKI in EGFR mutation-positive patients in lung cancer. We analysed the impact of EGFR mutation subtype, specifically, exon 19 and 21 on the PFS and OS of patients treated with pemetrexed (500 mg/m2 on day 1) and carboplatin (AUC 5 on day 1) as first-line therapy. Patients underwent axial imaging for response assessment on D42, D84, D126 and subsequently every two months till progression. Patients post-progression were treated with gefitinib.

Results: Fifty-one patients (36%) had exon 21 mutation, while 92 patients (64%) had exon 19 mutation. Response rates in evaluable patients was 47.7% in exon 19 patients (41 patients, n = 86) and 42.9 % in exon 21 patients (18 patients, n = 42). There was a significant increase in median overall survival for patients with exon 19 mutations (24.5 months, 95% CI: 21.3–27.7 months ) over the exon 21-mutated patients (18.1 months, 95% Cl: 13.5–22.6 months, p = 0.002). This differential impact was due to second-line gefitinib having a differential outcome on these mutations.

Conclusion: Pemetrexed-based chemotherapy does not have a differential impact on exon 19- or exon 21-mutated patients. However, second-line treatment with gefitinib has a favourable response and outcome in exon 19-mutated patients.

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