Subset of Patients With mCRPC Who Benefit From Radiopharmaceuticals Needs Definition

Targeted Therapies in Oncology, April 2019, Volume 8, Issue 5

Arjun V. Balar, MD, co-physician editor in chief of <em>Targeted Therapies in Oncology</em>, discusses&nbsp;recent data for bone-seeking radiopharmaceuticals in prostate cancer.

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.