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ONCAlert | Upfront Therapy for mRCC

Subset of Patients With mCRPC Who Benefit From Radiopharmaceuticals Needs Definition

Arjun V. Balar, MD
Published Online: Apr 04,2019

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.1 However, 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).3 In 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.

What strikes me about these data are the ability to potentially palliate disease-related symptoms in a population that typically is managed with best supportive care alone without cancer-directed therapy and, moreover, is classically excluded from clinical trials. A biomarker-directed approach makes particular sense because the ratio of risk to benefit for any treatment in this population must be weighed heavily to not worsen an already-devastating disease. Evidence from this trial supports potentially broader use of LuPSMA in patients with a poor prognosis, and other ongoing studies of LuPSMA are poised to make a substantial impact in the management of metastatic prostate cancer. Better-tolerated agents, furthermore, could serve as the basis for more promising combination strategies in the future. Radiopharmaceuticals certainly have a role in the management of advanced prostate cancer—just smarter ones.

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Subset of Patients With mCRPC Who Benefit From Radiopharmaceuticals Needs Definition
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