P3.02b-053 A Randomized, Open Label, Phase II Study Comparing Pemetrexed plus Cisplatin versus Pemetrexed Alone in EGFR Mutant NSCLC after EGFR-TKI: QOL Data: Topic: EGFR Clinical

Abstract

Various therapeutic strategies are available for NSCLC patients who develop disease progression on first-line EGFR-TKI. Platinum doublet is usually recommended, however, it has not been established which cytotoxic regimens are preferable for these patients. We conducted a prospective randomized phase II trial to compare the clinical outcomes between pemetrexed plus ciplatin combination therapy with pemetrexed monotherapy after failure of first-line EGFR-TKI. Patients with non-squamous NSCLC harboring activating EGFR mutation who have progressed on first-line EGFR-TKI were randomly assigned in a ratio of 1:1 to pemetrexed plus cisplatin or pemetrexed alone. Patients were treated with pemetrexed 500 mg/m2 and cisplatin 70 mg/m2 for four cycles, followed by maintenance pemetrexed as single agent every 3 weeks or treated with pemetrexed 500 mg/m2 monotherapy every 3 weeks until progression. Primary objective was PFS, and secondary objectives include overall response rate (ORR), OS, health-related quality of life (HRQOL), safety and toxicity profile. The HRQOL was assessed every 2 cycles by using EORTC QLQ-C30 and EORTC QLQ-LC13. 96 patients were randomized and 91 patients were treated at 14 centers in Korea. The characteristics of pemetrexed plus cisplatin (PC) arm (n=48) and pemetrexed alone (P) arm (n=48) were well balanced; the median age was 60 vs. 64 years old; 37 vs. 33 patients were females; 39 vs. 43 patients were ECOG PS 1. The ORR of PC arm (n=46) was 34.8% (16/46), while P arm (n=45) was 17.8% (8/45). With 20.4 (range 4.1-33.4) months of follow-up, the median PFS was 5.4 months (95% confidence interval [CI], 4.5-6.3) in PC arm and 6.4 months (95% CI, 3.6-9.2) in P arm (p=.313). One-year survival rate was 77% for PC arm, 68% for P arm, respectively. The most common adverse events include anorexia (n=34, 37.4%), nausea (n=24, 26.4%), neuropathy (n=10, 11.0%) and skin change (n=10, 11.0%). Adverse events ≥ Grade 3 were in 12 patients (26.1%) in PC arm and 8 patients (17.8%) in P arm. Dose reduction (5 vs. 2 patients) and dose delay (10 vs. 4 patients) were required more often in PC arm. With 385 pairs of questionnaire of EORTC QLQ-C30 and QLO-LC13 obtained from 94 patients, overall, the time trends of HRQOL were not significantly different between two arms. Further analysis of survival data will be updated. Pemetrexed plus cisplatin combination therapy showed higher response rate than pemetrexed monotherapy without significant difference in PFS. There was no significant difference in quality of life between two arms.