2008P - Assessing response durability and survival after second-line pembrolizumab in advanced urothelial carcinoma: A multicenter validation of a risk model

Background

Second-line pembrolizumab improves overall survival (OS) of patients (pts) with metastatic urothelial carcinoma (UC). We sought to develop and validate a risk model that can predict OS and duration of response after pembrolizumab.

Methods

We retrospectively analyzed pts with advanced UC treated with 2nd-line pembrolizumab post-platinum-based chemotherapy failure at a single institution (model creation cohort). We utilized univariate and multivariate Cox regression analyses to assess factors predicting time to progression (TTP). We sought to create a risk model depending on number of independent TTP predictors. The impact of risk groups on overall survival (OS) was examined. Validation utilized an independent dataset of pts from 59 centers. The impact of risk group on duration of response was assessed. Survival was estimated by Kaplan-Meier method, with statistical significance set at p < 0.05.

Results

The study comprised 565 pts (creation: 69; validation: 496). Factors predicting inferior TTP in multivariate analysis: interval from prior chemotherapy < 6 months (HR: 2.06, 95% CI: 1.16-3.66, p=0.014), liver metastasis (HR: 2.39, 95% CI: 1.29-4.45, p=0.009), and Eastern Cooperative Oncology Group Performance Status >1 (HR: 4.62, 95% CI: 2.42- 8.82, p< 0.001). In the creation cohort, median OS for pts in the favorable (0 risk factors), intermediate (1 risk factor), and poor risk (≥ 2 risk factors) groups were 29, 8.3, and 3.7 months respectively, p<0.001. The corresponding median OS times in the validation cohort were 21.6, 11.7, and 4.9 months respectively, p< 0.001. Among 538 pts evaluable for response, 174 (32%) had objective response. Median duration of response varied significantly by risk group; 38.9, 13.8, and 7.8 months for the favorable, intermediate, and poor risk groups respectively, p< 0.001.

Conclusions

We developed and validated a risk model that can predict durability of response and survival after 2nd-line pembrolizumab for advanced UC. Alternative systemic therapy is warranted for the poor risk group.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

S. Salah: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Janssen, Astellas. T. Kobayashi: Financial Interests, Personal, Invited Speaker: Janssen, Astellas, Bayer, MSD; Financial Interests, Personal, Advisory Board: Janssen, Astellas; Financial Interests, Institutional, Research Grant: Chugai. All other authors have declared no conflicts of interest.