Better prediction of favourable responses to immune checkpoint inhibitors in mUC

Response rates to treatment with immune checkpoint inhibitors are notoriously inconsistent, with some metastatic urothelial carcinoma (mUC) patients achieving durable responses and others not responding at all. Several patient characteristics may be used to predict better responses to immune checkpoint inhibitor therapy in urothelial carcinoma.

Dr Marie Alt (Princess Margaret Cancer Centre, Canada) and her team aimed to investigate whether any characteristics could be identified to predict which patients with urothelial carcinoma may have a better likelihood of achieving a favourable outcome with immune checkpoint inhibitors [1].

To this end, a retrospective, posthoc analysis was performed of data from 2 previous trials which investigated the use of durvalumab, an anti-PD-L1 monoclonal antibody, and durvalumab plus tremelimumab, an anti-CTLA-4 monoclonal antibody, in patients with mUC. The aim was to identify differences in patient characteristics between robust responders and poor responders.

Patients (n=367) were divided into 2 groups; one group consisting of patients who had survived ≥2 years (n=88; 24.0%), and the other group consisting of patients who had survived <2 years (n=279; 76.0%) from the point of receiving the first dose of the study drug. Next, a univariate analysis was performed on each baseline characteristic to identify any independent associations with long-term overall survival (OS). Finally, multivariate regression analysis was performed, including those variables that had been identified by univariate analysis. These consisted of sex, Eastern Cooperative Oncology Group Performance Status (ECOG PS), PD-L1 status, presence or absence of lymph node only disease, presence or absence of visceral disease, time from initial diagnosis to study entry, haemoglobin level, lactate dehydrogenase level, and absolute neutrophils count.

The primary outcome measure used in the analysis was long-term OS. Multivariate analysis revealed a significant association between long-term OS and ECOG PS, PD-L1 status, baseline haemoglobin level, and baseline absolute neutrophils count. Secondary outcome measures were objective response rates (ORR) and duration of response. Patients in the OS ≥2 years group had both higher ORR (71.6%) and longer duration of response than those in the OS <2 years group (ORR 5.7%).

Further investigation is warranted to determine what patient characteristics may predict a favourable response to immune checkpoint inhibitor therapy. Next steps should also explore if any biomarkers can be used to help inform prognosis.

1. Alt M. Identification of characteristics associated with long-term survival in patients with metastatic urothelial carcinoma (mUC) who received durvalumab (D) with or without tremelimumab (T) in clinical studies. Abstract 441, ASCO Genitourinary Cancers Symposium, 11–13 February 2021.

 

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Posted on 24 March 202117 May 2024