IMbassador250 Rules Out Atezolizumab For Metastatic CRPC

Author: By Lynda Williams, Senior medwireNews Reporter 

medwireNews: Negative findings for the IMbassador250 trial of enzalutamide plus atezolizumab for men with metastatic castration-resistant prostate cancer have been reported at the 2020 AACR Virtual Annual Meeting I. 

The phase III study’s participants had all previously progressed on abiraterone and had previously received, or were not candidates for, taxane chemotherapy, and were “well balanced across key clinical features”, explained presenting author Christopher Sweeney, from Dana-Farber Cancer Institute in Boston, Massachusetts, USA. 

The primary endpoint of overall survival (OS) was a median of 15.2 months for the 379 participants who were randomly assigned to receive enzalutamide 160 mg/day alongside atezolizumab 1200 mg every 3 weeks. 

This did not significantly differ from the median OS of 16.6 months achieved by the 380 men who received only the antiandrogen agent. The 12-month OS rates for the combination and enzalutamide monotherapy arms were 60.6% and 64.7%, respectively. 

There was also no significant difference between the treatment arms when assessing subgroups of patients, according to PD-L1 expression, prior receipt of docetaxel or local therapy or the presence of measureable disease and visceral metastases. 

Furthermore, the combination and monotherapy arms were comparable in terms of radiographic progression-free survival (4.2 vs 4.1 months) and time to prostate-specific antigen (PSA) progression (2.8 vs 2.8 months). 

An objective response was achieved by 14% of the patients given enzalutamide plus atezolizumab and 7% of those given only enzalutamide, while stable disease was reported for a corresponding 42% and 41%. A PSA response occurred in 26% and 24% of patients, respectively. The median duration of response was 12.4 months with the combination regimen and not reached with enzalutamide monotherapy.  

Overall, 78% of patients given the combination regimen experienced treatment-related adverse events (TRAEs), as did 51% of those given only enzalutamide. Grade 3–4 TRAEs occurred in 28% and 10% of patients, respectively, including serious TRAEs in 14% and 3%, and grade 5 TRAEs in 2% and less than 1%. 

“The overall safety profile of the combination was consistent with each individual treatment”, commented Christopher Sweeney, noting that 12.2% of atezolizumab-treated patients experienced a grade 3–5 immune-related AE, most commonly rash (7.5%) and hypothyroidism (<1%), versus just 1.3% of those treated with enzalutamide alone. 

“Biomarker studies are ongoing and may provide further insight into these findings”, he concluded. 

Reference 

Sweeney C, Gillessen S, Rathkopf D, et al. CT014: IMbassador250: a phase III trial comparing atezolizumab with enzalutamide vs enzalutamide alone in patients with metastatic castration-resistant prostate cancer. American Association of Cancer Research Virtual Annual Meeting I; 27–28 April 2020 (Abstract CT014).