Dr. Yu on Initial Findings From the KEYNOTE-365 Trial in mCRPC

Evan Y. Yu, MD, professor, Department of Medical Oncology, University of Washington School of Medicine, member, Clinical Research Division, Fred Hutchinson Cancer Research Center, and clinical trials core director, Genitourinary Medical Oncology, Seattle Cancer Care Alliance, discusses initial findings from the phase Ib/II KEYNOTE-365 trial in metastatic castration-resistant prostate cancer (mCRPC).

Patients who enrolled in the trial were heavily pretreated; about 25% of patients received abiraterone acetate (Zytiga), enzalutamide (Xtandi), docetaxel, and cabazitaxel (Jevtana). The response rates were modest but reasonable given that it was a molecularly unselected group. Among the patients with soft tissue disease, 14% had a significant prostate-specific antigen (PSA) decline. In the overall population, 12% of patients had a significant PSA decline. According to the waterfall plots, 29% of patients who had soft tissue disease had significant shrinkage of greater than 30% in their target lesions. However, the confirmed objective response rate was only 7%, says Yu.

RECIST 1.1 is difficult to confirm in prostate cancer if patients have nontarget lesions like bone metastases or bone scans that look worse. That is what happened in the patients who had those responses other than 1; they had progression in nontarget lesions and bone lesions, explains Yu. Whether that was a healing flare and patients were still responding is unclear. Patients are more likely to experience durable responses from immunotherapy than they are short-term responses and then progressive disease somewhere else. Therefore, there may have been healing in the bone that wasn’t being labeled as a confirmed response. This may be a result of different bone and soft tissue microenvironments. However, the hypothesis that the combination may work better for soft tissue will have to be validated, concludes Yu.