Radium-223 Before Docetaxel Demonstrates Better QOL in mCRPC, With No Difference in Survival

Administering radium-223 (Xofigo) prior to docetaxel resulted in improved quality of life (QOL) and tolerability compared with the reverse sequence in patients with symptomatic, bone-dominant metastatic castration-resistant prostate cancer (mCRPC), according to data from the phase 2 RAPSON trial (NCT03230734). Additionally, no significant differences were observed in progression-free survival (PFS) or overall survival (OS) between the two treatment sequences, as presented at the 2024 ESMO Congress.¹

At week 12 of the trial, investigators noted a change in the QOL scores from the Functional Assessment of Cancer Therapy-Prostate (FACT-P) in patients who received docetaxel followed by radium-223. Investigators noted significant worsening of health-related QOL (HRQOL) for patients who received docetaxel prior to radium-223 between baseline and the week 12 evaluation. In addition, a descriptive analysis of HRQOL measures noted significant worsening in patients in the chemotherapy arm between baseline and 12-week evaluation. QOL characteristics were also assessed, including FACT-General, physical, social, emotional, and functional well-being, and prostate symptoms.

RAPSON was an open-label, multicenter, randomized study evaluating symptomatic bone-dominant patients with mCRPC with 2 or more bone metastases who have experienced disease progression after any androgen deprivation therapy. To be eligible, patients could not have received prior chemotherapy for CRPC.

In the 2-step trial, patients were randomly assigned to receive either 6 repeated monthly injections of radium-223 at 55 kBq/kg (arm A; n = 34) or 10 cycles of docetaxel at 75 mg/m2 every 3 weeks plus 5 mg prednisone twice daily (arm B; n = 36). Upon disease progression, patients in arm A received docetaxel and patients in arm B received radium-223 (step 2).

“The second step is optional according to the clinical evolution of the disease, [which] includes onset of visceral metastasis or poor clinical conditions,” Vincenza Conteduca, MD, PhD, lead author and associate professor, Department of Medical and Surgical Sciences, University of Foggia in Italy said during the presentation.

The primary objective of the trial was change in HRQOL and secondary objectives include PFS, total PFS, OS, safety, and the identification of biomarkers. Investigators reported that the HRQOL benefit was determined using the FACT-P; bone pain was assessed using the Brief Pain Investigatory-Short Form (BPI-SF).

Patients who experienced a QOL increase in the minimally important difference from baseline at week 12 were considered responders, whereas patients experiencing a decrease in HRQOL score were considered to have experienced worsening HRQOL.

Further responder analysis to the BPI-SF showed a higher incidence of pain intensity and interference with daily activities among responders who received radium-223 prior to chemotherapy.

Reviewing data on treatment reduction and discontinuation, investigators reported that more patients in arm B experienced treatment reduction than patients in arm A (9 patients vs 1 patient, or 25% vs 3%). Nineteen percent of patients in arm B experienced hematological toxicity leading to treatment reduction vs none in arm A, and treatment reduction caused by non-hematological toxicity affected 2.9% of patients in arm A vs 5.6% of patients in arm B.

Regarding treatment discontinuation due to drug-related adverse events in step 1, 19.4% of patients in arm B and 5.9% of patients in arm A discontinued treatment.

In step 1, overall median PFS was 7.7 months (95% CI, 6.5-13.4). Evaluating arm A and B reveals that median PFS for arm A was 7.3 months (95% CI, 3.3-11.0) and for arm B was 9.7 months (95% 6.7-12.5; P = .74). “This difference was not significant,” Conteduca said.

Overall median OS, determined by combining step 1 and step 2, was 17.4 months (95% CI, 12.0-NR). For arm A, overall median OS was not reached and for arm B it was 17.4 months (95% CI, 10.1-NR; P = .964).

“The RAPSON trial provides preliminary evidence to support the use of radium-223 prior to chemotherapy in bone-dominant symptomatic mCRPC, with a clinical benefit in terms of better QOL and tolerability,” Conteduca said. “Additional follow-up and ongoing identification of biomarkers might allow for a more personalized approach to this sequential strategy,” she concluded.

Reference

Conteduca V, Brighi N, Gurioli G, et al. Open-label multicenter randomized trial of Radium223-docetaxel versus docetaxel-Radium223 sequence in metastatic castration resistant prostate cancer (RAPSON study) with prospective biomarker evaluation. Presented at: 2024 ESMO Congress; September 13-17, 2024; Barcelona, Spain. Abstract LBA71.