Paclitaxel and carboplatin after disease progression on immune checkpoint inhibitor for patients with metastatic urothelial carcinoma.

AIM: Despite advances with immune checkpoint inhibitor (ICI)-based regimens in the past decade, patients with metastatic urothelial cancer (mUC) face a poor prognosis with few approved options. Platinum-based chemotherapy with paclitaxel and carboplatin (TC) +/- ICI may be a feasible choice.

METHODS

We generated an IRB-approved, HIPAA-compliant retrospective database of patients at Mayo Clinic Cancer Center with mUC who started TC +/- ICI after disease progression on ICI from January 2018 through December 2024. Baseline demographics, clinicopathologic features, and treatment outcomes were extracted from the electronic health record. Kaplan-Meier method was used to calculate median duration of response (DOR), progression-free survival (PFS) and overall survival (OS).

RESULTS

There were 32 patients who fit inclusion criteria, including 31 patients who had disease progression on ICI in the metastatic setting and 1 patient who developed metastatic disease on adjuvant nivolumab. Patients received a median of 4 cycles (range 1-14) of TC over median 12 weeks (range 3-53). Overall, 81% of patients received TC concurrently with an ICI, and 28% continued maintenance ICI after TC discontinuation (at the treating oncologist's discretion due to adequate response or toxicity). The best objective response rate was 41% and disease control rate was 75%, with median DOR of 4.8 months (IQR 2.7-10.4), median PFS of 4.6 months (IQR 3.3-10.2), and median OS of 9.4 months (IQR 6.3-15.9). Some patients in this series had very durable responses with PFS > 12 months and OS > 24 months. TC +/- ICI was overall well tolerated with expected type and severity of adverse events.

CONCLUSIONS

Strategies to overcome ICI resistance are needed, and TC +/- ICI after disease progression on an ICI shows promising tolerability and efficacy in this setting for patients with mUC. Our series was notable for some patients having a durable response. Validation in larger cohorts is warranted.