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 IV 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: 43-90) and 66 (range33-82), respectively, with 63% and 73% of patients being male, respectively. The median PFS was 6.0 months (95% CI, 3.4-8.5) with pemetrexed versus 2.3 months (1.8-2.7) with observation (p=0.044, HR 0.64; 95% CI, 0.41-0.99). The median OS was 18.1 months (95% CI, 6.9-29.4) for pemetrexed and 17.9 months (16.1-19.7) for observation (p=0.913, HR 1.03; 95% CI, 0.61-1.73). Common adverse events in the pemetrexed group included anemia (30%), fatigue (18%), and neutropenia (12%), 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.