A randomized, open label, phase II study comparing pemetrexed plus cisplatin followed by pemetrexed versus pemetrexed alone in EGFR mutant NSCLC patients who have failed first-line EGFR TKI: KCSG-LU12-13

Various therapeutic strategies are available for non–small-cell lung cancer (NSCLC) patients who develop disease progression on first-line EGFR tyrosine kinase inhibitor (TKI) therapy. However, it has not been established which cytotoxic regimens are preferable for these patients. Yoo and colleagues conducted a prospective randomized phase 2 trial to assess the clinical outcomes with pemetrexed plus cisplatin (PC) combination therapy compared with pemetrexed monotherapy after failure of first-line EGFR TKI.¹ Patients with advanced (stage IIIB) or metastatic (stage IV) nonsquamous NSCLC harboring activating EGFRmutation (del 19 or L858R mutation) who had progressed on first-line EGFR TKI were randomly assigned in a ratio of 1:1 to the PC arm or pemetrexed arm, and were treated with pemetrexed 500 mg/m² and cisplatin 70 mg/m² for 4 cycles, followed by pemetrexed maintenance every 3 weeks, or treated with pemetrexed 500 mg/m² monotherapy every 3 weeks until progression of disease. The primary clinical end point was progression-free survival (PFS), and secondary end points included overall response rate, overall survival, quality of life (QOL), and the safety profile. A total of 96 patients were randomized, and 91 patients were treated. At 20.4 months of median follow-up, the median PFS was 5.4 months (95% confidence interval [CI], 4.5-6.3) in the PC arm and 6.4 months (95% CI, 3.6-9.2) in the pemetrexed arm (P = 0.313). The 1-year survival rate was 77% for the PC arm and 68% for the pemetrexed arm. The most common adverse events included anorexia (37%), nausea (26%), neuropathy (11%), and skin change (11%). Adverse events ≥grade 3 were in 12 (26%) patients in the PC arm and 8 (18%) patients in the pemetrexed arm, and dose reduction and delay were required more often in the PC arm. The authors concluded that PC combination therapy showed a higher response rate than pemetrexed monotherapy. However, there was no significant difference in PFS between the 2 arms, and that further genetic and molecularly based analyses are warranted to evaluate the contributing factors for long-term responders. While the authors promised that QOL data would be presented at ASCO 2016, QOL analyses were not available at the meeting.

1. Yoo KH, et al. ASCO 2016. Abstract 9043.