Combination of radium-223 and enzalutamide benefits patients with mCRPC with bone metastases

The first results from the phase 3 PEACE-3 study demonstrated that combining enzalutamide and radium-223 treatment improved both radiological progression-free survival (PFS) and overall survival (OS) in men with metastatic castration-resistant prostate cancer (mCRPC) and bone metastases.

In patients with mCRPC progression on androgen deprivation therapy (ADT), abiraterone and enzalutamide are standard-of-care first-line treatment options [1,2]. Treatment with radium-223 has also shown to increase OS in this population [3]. However, the combination of radium-223 and abiraterone has previously not shown any benefit in OS or event-free survival [4].

The randomised phase 3 PEACE-3 study (NCT02194842) investigated whether combining enzalutamide and radium-223 improves survival over enzalutamide alone in patients with mCRPC. The trial enrolled 446 participants with bone metastases and no prior treatment with enzalutamide, who were 1:1 randomised to enzalutamide plus radium-223 or enzalutamide alone. The use of bone-protecting agents was mandatory. The primary endpoint was radiological PFS. Prof. Silke Gillessen (Oncology Institute of Southern Switzerland) presented the first results [5].

Adding radium-223 to enzalutamide significantly improved median radiological PFS: 19.4 versus 16.4 months (HR 0.69; 95% CI 0.54–0.87; P=0.0009). The radiological PFS rate at 24 months improved from 36% to 45%. In addition, median OS was significantly improved by radium-223: 42.3 versus 35.0 months (HR 0.69; 95% CI 0.52–0.90; P=0.0031). Radium-223 also improved the time to next systemic treatment (HR 0.57; 95% CI 0.44–0.75; P<0.0001) but not the time to symptomatic skeletal event (HR 0.93; 95% CI 0.62–1.38). The combination therapy was generally well tolerated; discontinuation due to toxicity was 11%, versus 7% in the enzalutamide alone arm. Drug-related grade ≥3 adverse event rates were 28% and 19%, respectively.

“These results support the combination of enzalutamide plus radium-223 as a potential first-line treatment option for patients with mCRPC and bone metastases who have not received a prior androgen-receptor pathway inhibitor,” Prof. Gillessen concluded.

1. Ryan CJ, et al. N Engl J Med 2013;368:38-148.
2. Beer TM, et al. N Engl J Med 2014;371:424-433.
3. Parker C, et al. N Engl J Med 2013;369:213-223.
4. Smith M, et al. Lancet Oncol. 2019;20:408-419.
5. Gilessen S, et al. A randomized multicenter open label phase III trial comparing enzalutamide vs a combination of Radium-223 (Ra223) and enzalutamide in asymptomatic or mildly symptomatic patients with bone metastatic castration-resistant prostate cancer (mCRPC): First results of EORTC-GUCG 1333/PEACE-3. Abstract LBA1, ESMO Congress 2024, 13–17 September, Barcelona, Spain.

 

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Posted on 4 November 20244 November 2024