Pemetrexed Maintenance versus Observation in Patients with Advanced Urothelial Carcinoma Who Completed First-Line Platinum-Based Chemotherapy without Disease Progression (PREMIER, KCSG GU16-05)

Purpose Platinum-based chemotherapy is the standard treatment for advanced urothelial carcinoma (aUC). Switch maintenance therapy after first-line (1L) treatment may delay disease progression. This study evaluated pemetrexed as switch maintenance therapy versus observation in aUC patients without disease progression after initial chemotherapy. Materials and Methods Eligible aUC patients who did not progress after 4-6 cycles of cisplatin or carboplatin-based chemotherapy were randomized 1:1 to receive maintenance pemetrexed (500 mg/m² intravenously every 3 weeks, up to 16 cycles) or observation. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), response rate, and safety. Results The trial was closed early due to slow accrual after avelumab approval. From October 2016 to December 2022, 97 patients were randomized to pemetrexed (n=49) or observation (n=48). The median age was 69 years (range, 43 to 90) and 66 (range, 33 to 82), respectively, with 63% and 73% of patients being male, respectively. The median PFS was 6.0 months (95% confidence interval [CI], 3.4 to 8.5) with pemetrexed versus 2.3 months (95% CI, 1.8 to 2.7) with observation (p=0.044; hazard ratio [HR], 0.64; 95% CI, 0.41 to 0.99). The median OS was 18.1 months (95% CI, 6.9 to 29.4) for pemetrexed and 17.9 months (95% CI, 16.1 to 19.7) for observation (p=0.913; HR, 1.03; 95% CI, 0.61 to 1.73). Common adverse events in the pemetrexed group included anemia (30.6%), fatigue (18.4%), and neutropenia (12.2%), primarily grade 1 or 2. Conclusion The PREMIER trial showed that switch maintenance pemetrexed significantly prolonged PFS in aUC patients post-1L platinum-based chemotherapy, with a favorable safety profile. Further studies on combination maintenance therapies are warranted.