The combination of atezolizumab with enzalutamide resulted in similar overall survival (OS) as enzalutamide alone among men with metastatic or locally advanced, incurable castration-resistant prostate cancer (CRPC), according to results from the phase 3 IMbassador250 trial presented at the 2020 American Association for Cancer Research (AACR) Virtual Annual Meeting I.

The rationale behind this combination was based on the potential of enzalutamide to increase interferon-gamma secretion, thereby sensitizing tumor cells to immune-mediated cell killing. Therefore, the purpose of this trial was to determine if combining enzalutamide with an immune checkpoint inhibitor could improve efficacy for patients with mCRPC.

“There was no evidence that atezolizumab added to enzalutamide as treatment for men with mCRPC after prior abiraterone led to improvement in OS,” Christopher Sweeney, of the Dana-Farber Cancer Institute, Boston, Massachusetts, and lead author and presenter of the study, said.

The phase 3 IMbassador 250 trial randomly assigned 759 patients with mCRPC, or locally advanced or incurable CRPC, to receive atezolizumab plus enzalutamide or enzalutamide alone until loss of clinical benefit or unacceptable toxicity. The primary endpoint was OS and the key secondary endpoints were OS at 12 and 24 months, radiographic progression-free survival (rPFS), prostate-specific antigen (PSA) response time, time to PSA progression, objective response rate (ORR), duration of response (DOR) in soft-tissue lesions, and safety.


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At an interim analysis, the independent data monitoring committee declared futility and the trial was stopped — but no new safety concerns were identified.

Baseline characteristics were similar between arms, with a median patient age of 70 years; 55% of patients had previously received a taxane-containing therapy and 64% had previously received a local therapy. Measurable disease was present in 35% of patients at baseline.

There was no difference in OS between arms, with a median of 15.2 months (95% CI, 14.0-17.0 months) with atezolizumab plus enzalutamide compared with 16.6 months (95% CI, 14.7-18.4 months) with enzalutamide alone (hazard ratio [HR], 1.12; 95% CI, 0.91-1.37; P =.28). This lack of benefit was observed across subgroups. The 12-mo OS rate was 60.6% with atezolizumab plus enzalutamide compared with 64.7% with enzalutamide alone.

rPFS was also similar between treatment arms, with a time to rPFS of 4.2 months with atezolizumab plus enzalutamide compared with 4.1 months with enzalutamide alone (HR, 0.90; 95% CI, 0.75-1.07). Time to PSA progression was 2.8 months for both arms.

ORR was 14% with atezolizumab plus enzalutamide compared with 7% with enzalutamide, with a median DOR that was 12.4 months with the atezolizumab combination and not estimable with enzalutamide alone.

Dr Sweeney said that “PD-L1 expression did not identify a population of patients who benefited from the combination.”

The adverse events (AEs) were consistent with those observed with the individual agents, but occurred more frequently with the combination. Treatment-related AEs occurred in 77.9% of patients in the atezolizumab plus enzalutamide arm compared with 51.1% in the enzalutamide arm. Grade 3 to grade 4 treatment-related AEs occurred in 28.3% of patients in the combination arm compared with 9.6% of patients in the enzalutamide arm.

“IMbassador250 was the first phase 3 trial to investigate a checkpoint inhibitor combination in mCRPC and revealed no evidence of difference in cancer control between arms,” Dr Sweeney concluded.

Discussant Padmanee Sharma, MD, PhD, of The MD Anderson Cancer Center in Houston discussed several reasons that the addition of an anti–PD-L1 antibody did not improve the efficacy of enzalutamide, highlighting that prostate cancers are “cold tumors with few T cells” and there is “very little to no expression of PD-L1 and PD-1.”

Disclosures: Some of the presenting authors disclosed financial relationships with pharmaceutical and/or medical companies. For a full list of disclosures, please refer to the study abstract.

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Reference

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

This article originally appeared on Cancer Therapy Advisor