Subset of Patients With mCRPC Who Benefit From Radiopharmaceuticals Needs Definition

Arjun V. Balar, MD

The mangement of bone metastases in men with metastatic prostate cancer has been a clinical challenge for decades. Men with advanced prostate cancer experience disease-related morbidity from bone metastases in the form of severe and debilitating bone pain as well as fatigue due to cytopenias from marrow infiltration.

Bone-seeking radiopharmaceuticals have been in development for years and, in the case of radium-223 (Xofigo), have achieved regulatory approval. Interestingly, the phase III ALSYMPCA study demonstrated not only an improvement in pain from bone metastases but also a modest survival benefit when added to standard-of-care prostate cancer management, suggesting that direct targeting of bone metastases in prostate cancer would lead to overall improved outcomes.¹However, toxicity of such an approach is also of paramount importance; recent data from a separate phase III trial of radium 223 versus placebo added to standard abiraterone plus prednisone as first-line treatment in men with metastatic castration-resistant prostate cancer (CRPC) suggested worse survival and an increase in bone fractures with the combination.²

Notably, patients included in this study had no or only mild symptoms related to prostate cancer bone metastases. Because of these data, use of radium-223 is recommended only in men with significant symptoms due to prostate cancer bone metastases and without concurrent abiraterone/prednisone.

Other novel agents, however, may have better traction in this disease and I’m particularly excited about prostate-specific membrane antigen (PSMA)—targeted agents using a biomarker-directed approach. Interesting data from a small study of lutetium Lu 177 (Lu)PSMA were presented at the European Society for Medical Oncology 2019 International Congress on Targeted Anticancer Therapies (see page 22).³In this trial, 22 men with advanced CRPC with PSMA-expressing cancer and significant disease-related morbidity were treated with a single cycle of LuPSMA. The mean ECOG performance status (PS) of patients enrolled was 3.3 with a mean visual analog scale for pain score of 5.2 (on a 10.0-point scale) indicative of a population with a poor prognosis. Interestingly, 6 patients experienced an improvement in ECOG PS, and 12 patients reported improvement in pain with no significant added toxicity. Twenty-two percent of patients had a response in prostate-specific antigen levels.