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 EGFR
mutation (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.
- Yoo KH, et al. ASCO 2016. Abstract 9043.