IMbassador250: Atezolizumab–enzalutamide strikes out in mCRPC
medwireNews: The phase 3 IMbassador250 trial has failed to show any significant improvement in metastatic castration-resistant prostate cancer (mCRPC) outcomes with the addition of atezolizumab to enzalutamide.
The investigators hypothesized that enzalutamide could be a candidate for combination with anti-PD-1 or anti-PD-L1 agents as it “may enhance IFNɣ signaling and sensitize tumor cells to immune-mediated cell killing.”
However, there was no significant improvement in overall survival (OS) or other outcomes with the addition of the PD-L1 inhibitor atezolizumab to enzalutamide, and the trial was terminated early, reported Christopher Sweeney (Dana-Farber Cancer Institute, Boston, Massachusetts, USA) on behalf of his collaborators at the 2020 AACR Virtual Annual Meeting I.
Interview: IMbassador250 investigator Christopher Sweeney outlines the main results of the trial.
The trial included 759 mCRPC patients who had either progressed on abiraterone plus docetaxel or were ineligible for taxane-based therapy. The men were randomly assigned to receive atezolizumab 1200 mg every 3 weeks either with or without enzalutamide 160 mg/day.
After a minimum follow-up of 11.0 months, the primary endpoint of OS was comparable between the study arms, at a median of 15.2 months for participants given atezolizumab plus enzalutamide and 16.6 months for those treated with enzalutamide alone. The 12-month OS rates were 60.6% and 64.7%, respectively.
The findings were consistent across all prespecified subgroups, including by prior docetaxel or local therapy status and PD-L1 expression levels.
Interview: Padmanee Sharma provides an independent comment on the IMbassador250 trial.
And there was no significant improvement in other endpoints, such as radiographic progression-free survival or time to prostate-specific antigen progression, with the combination versus enzalutamide alone.
Sweeney commented that “the overall safety profile of the combination was consistent with each individual treatment,” but the incidence of side effects tended to be higher in the combination than enzalutamide monotherapy arm.
Treatment-related adverse events (TRAEs) of any grade occurred in 77.8% of patients in the combination group and 51.1% of those in the enzalutamide monotherapy group, with grade 3–4 events in 28.3% and 9.6%, respectively, and grade 5 events in a corresponding 1.9% and 0.3%.
Fourteen percent of men given atezolizumab plus enzalutamide discontinued any therapy component, as did 6% of their counterparts given enzalutamide alone.
In conclusion, Sweeney said: “Biomarker studies are ongoing and may provide further insights into these findings.”
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