Characteristics of Patients With Advanced or Metastatic Urothelial Cancer Unable to Complete Six Cycles Chemotherapy

The optimal number of chemotherapy cycles prior to maintenance avelumab in frontline metastatic urothelial cancer (mUC) remains unknown. We hypothesize that baseline characteristics can identify which patients will complete six cycles of chemotherapy without radiographic disease progression, versus those who may benefit from stopping chemotherapy earlier and switching to maintenance avelumab.

A retrospective audit was performed at Barts Cancer Centre for consecutive patients from January 2010 until August 2023. Patients who received frontline chemotherapy for mUC were included. Patients who completed six cycles of chemotherapy without radiographic disease progression (PD) were compared to those who discontinued treatment earlier or progressed during chemotherapy. Baseline characteristics and treatment factors were compared between patient groups using chi-squared tests (SPSS v29).

194 patients receiving frontline platinum-based chemotherapy were identified. Only 85 of 193 patients (44%) completed six cycles without progression. Baseline characteristics were broadly comparable between patients who completed six cycles and those who did not, including ECOG performance status 0-1 (84% vs. 76%), presence of liver metastases (17% vs. 22%), baseline hemoglobin < 100 g/L (6% vs. 19%), and cisplatin use (59% vs. 54%), respectively. Early dose reduction (DR) prior to cycle 4 was the only factor significantly associated with failure to complete six cycles of chemotherapy without PD (14% vs. 43%, p < 0.001). Among patients requiring early dose reduction, only 19% subsequently completed six cycles without progression, while 43% progressed before reaching cycle 6, with a median PFS of 3 months (95% CI: 2.4-4.1).

Baseline characteristics do not reliably predict the ability to complete six cycles frontline chemotherapy in mUC. However, early dose reduction in the first four cycles highly predicted inability to complete six cycles of chemotherapy.