Dr. Sawyers on the Negative Results of the IMbassador250 Trial in mCRPC

Charles L. Sawyers, MD, internist and hematologic oncologist; chair of the Human Oncology and Pathogenesis Program; and Marie-Josée and Henry R. Kravis Chair at Memorial Sloan Kettering Cancer Center, discusses the negative results of the phase 3 IMbassador250 trial in metastatic castration-resistant prostate cancer (mCRPC).

The clinical trial evaluated the safety and efficacy of atezolizumab (Tecentriq) in combination with enzalutamide (Xtandi) versus enzalutamide alone in patients with mCRPC. Results showed that the overall survival (OS) was not different between groups (stratified HR, 1.12; 95% CI, 0.91-1.37; P =.28). Specifically, the median OS was 15.2 months (95% CI, 14.0-17.0) in the combination arm and 16.6 months (95% CI, 14.7-18.4) in the enzalutamide-alone arm. The trial was done in patients with late stage prostate cancer, says Sawyers, who added that it may have been too late to hope for an immune response to be activated.

Investigators at the University of Texas MD Anderson Cancer Center have shown that immunotherapy can be given to patients at the time of diagnosis, prior to surgery, adds Sawyers. For a certain set of patients who have locally advanced or aggressive disease, it is meaningful to evaluate new therapies in an effort to improve their chance of cure following surgery. Investigators have shown that it is possible to elicit an immune response if patients are treated early, says Sawyers.

Another important point to remember is that it really matters which immune checkpoint inhibitor is used, adds Sawyers. Many consider CTLA-4, PD-1, and PD-L1 to be interchangeable; however, CTLA-4 is quite different in terms of how it regulates the immune system. PD-1 and PD-L1 work primarily locally at the site and can impact T-cells that are already in the tumor; CTLA-4 can help recruit T-cells to the tumor, explains Sawyers. In retrospect, treating patients earlier in the disease course or perhaps utilizing a CTLA-4 instead of PD-L1 or a combination might have been more effective, concludes Sawyers.