Radium223, chemotherapy improves mCRPC quality of life in phase 2 RAPSON

Nicole Brighi, MD, PhD

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Radium223 (Xofigo), a calcium mimetic radioactive therapy indicated to treat prostate cancer, may be a particularly beneficial symptom-treating therapy as a regimen prior to chemotherapy in patients with bone-dominant metastatic, castration-resistant prostate cancer (mCRPC), according to new phase 2 trial data.

Findings from the RAPSON trial, presented at the European Society for Medical Oncology (ESMO) 2024 Scientific Sessions in Barcelona, Spain this week, showed Radium223 preceding chemotherapy resulted in better patient-reported tolerability, fewer dose reductions and improved quality of life measures than regimen of chemotherapy then Radium223 in patients with mCRPC.

The RAPSON data, presented at ESMO 2024 by study author Nicole Brighi, MD, PhD, a postdoctoral research fellow at the UCL Cancer Institute, provide clinical evidence toward advancing Radium223 assessment in the treatment of patients with mCRPC—a form of cancer that results in more than 40,000 new cases annually.

Brighi and colleagues conducted the prospective, multicenter, randomized phase 2 trial assessing combinations of Radium223 and chemotherapy in successive orders to interpret best outcomes for quality of life, safety and tolerability. “Defining the most effective treatment sequence between α emitter Radium223 and docetaxel is pivotal for optimizing bone-dominant mCRPC outcomes,” the team noted.

Eligible patients with symptomatic, bone-dominant mCRPC who progressed after androgen deprivation therapy with or without abiraterone or enzalutamide were randomized 1:1 to either initial Radium223 or docetaxel, followed by the other treatment. Investigators sought a primary endpoint of percentage of patients experiencing health-related quality of life changes per the Functional Assessment of Cancer Therapy Prostate (FACT-P) questionnaire—a 39-item, self-administered patient survey that assess sub-domains of physical, social, familial, emotional and functional wellbeing in patients with prostate cancer

Investigators defined patients with a FACT-P score increase at least equivalent to the minimally important difference range at 12 weeks to be responders to therapy, whereas those with a decrease below that range in that time were non-responders.

The data presented at ESMO 2024 included 70 patients followed up with for a median 13 months (range, 4 – 45). A preliminary analysis of the FACT-P responder scores showed one-third (33%) of patients receiving Radium223 then docetaxel experienced a worsening in score, versus 50% of patients in the comparator arm. Man change in FACT-P total scores at week 12 was 4 for the Radium223 arm, versus 7.87 for the docetaxel arm (mean difference, 3.87; 95% CI, -9.14 to 16.88).

“Radium223 then docetaxel resulted in an improvement of quality of life compared to docetaxel then Radium223, also in terms of better tolerability (2 vs 7 discontinuations, and 1 vs 9 dose reductions related to Radium223 versus docetaxel, respectively),” investigators wrote.

Efficacy data additionally showed no significant different in progression-free survival and overall survival between the treatment arms, despite only 14 patients having completed the second stage of therapy at the time of the data presentation. Brighi and colleagues concluded their findings show a clear benefit of specific strategy with the radioactive therapy plus chemotherapy going forward.

“(The) RAPSON trial provided evidence to support the use of Radium223 prior to chemotherapy in bone-dominant symptomatic mCRPC with a clinical benefit in terms of better quality of life and tolerability,” they wrote.

References

1. ^{Brighi N, Gurioli G, Wetterskog D, Giunta EF, et al. Open-label, multicentre randomised trial of Radium223-docetaxel versus docetaxel-Radium223 sequence in metastatic castration resistant prostate cancer (mCRPC) with prospective biomarker evaluation (RAPSON study). Poster presented: ESMO Congress 2024. Barcelona, Spain. September 13 – 17, 2024.}
2. ^{FACIT. FACT-P: Functional Assessment of Cancer Therapy – Prostate. Website. https://www.facit.org/measures/fact-p}