LBA71 - 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)

Background

Defining the most effective treatment sequence between α emitter Radium223 and docetaxel is pivotal for optimizing bone-dominant mCRPC outcomes.

Methods

RAPSON is a prospective, multicentre, randomized phase 2 trial in 70 patients (pts) with symptomatic bone-dominant mCRPC who progressed after androgen deprivation therapy ± abiraterone or enzalutamide. Pts were initially randomized 1:1 to receive Radium223 or docetaxel as first treatment followed by docetaxel or Radium223, respectively, at progression. The primary endpoint was the impact of sequential therapy on the percentage of pts with symptomatic bone-dominant mCRPC experiencing changes in health-related quality of life (QoL) measured with the Functional Assessment of Cancer Therapy Prostate (FACT-P) questionnaire from baseline to week 12. The upper limit of the minimally important difference (MID) range was used to evaluate these changes. Pts experiencing a QoL increase ≥MID of FACT-P questionnaire were considered responders, whereas pts experiencing a decrease in QoL score ≥MID were considered no responders.

Results

At median follow-up of 13 months (range 4-45), a preliminary responder analysis at week 12 showed 33% vs 50% of pts experiencing a worsening of FACT-P questionnaire score (22% vs 50% in the physical well-being subscale) in Radium223 vs docetaxel arm, respectively. The mean change in FACT-P total scores from baseline to week 12 was 4 [Standard Deviation (SD) 16.84 for Radium223 and 7.87 (SD 14.08) for docetaxel, with a difference between groups of 3.87 (95% CI -9.14 to 16.89). Radium223 -> docetaxel resulted in an improvement of QoL compared to docetaxel -> Radium223, also in terms of better tolerability (2 vs 7 discontinuations, and 1 vs 9 dose reductions related to Radium223 vs docetaxel, respectively). Efficacy results reported no difference in PFS and OS between Radium223 and docetaxel evaluated only for step 1 as only 14 pts completed step 2 so far.

Conclusions

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 QoL and tolerability.

Clinical trial identification

NCT03230734.

Editorial acknowledgement

Legal entity responsible for the study

IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy.

Funding

Bayer.

Disclosure

V. Conteduca: Financial Interests, Personal, Advisory Board: Janssen, Astellas, Bayer, Recordati, Eisai, Amgen, Novartis; Financial Interests, Personal, Invited Speaker: AstraZeneca, Merck, Ipsen, GSK, BMS. N. Brighi: Financial Interests, Personal, Other, Travel support: Janssen, Ipsen, Novartis, Pfizer; Financial Interests, Personal, Speaker’s Bureau: BMS; Financial Interests, Personal, Advisory Board, Travel support: Advanced Accelerator Application. E.F. Giunta: Financial Interests, Personal, Other, Travel support: Janssen, Bayer. V.E. Chiuri: Financial Interests, Personal, Advisory Board: Janssen, Ipsen, Bayer. D. Gasparro: Financial Interests, Personal, Advisory Board: Bayer. P.A. Zucali: Financial Interests, Personal, Advisory Board: Janssen, Astellas, MSD, Sanofi, Ipsen, Pfizer, Novartis, AstraZeneca, Amgen, Roche, Bayer. G. Attard: Financial Interests, Personal, Speaker, Consultant, Advisor: Janssen, Novartis, Astellas, Pfizer, AstraZeneca, Bayer, Sanofi, Orion; Financial Interests, Institutional, Research Grant: Artera; Financial Interests, Personal and Institutional, Research Grant: Blue Earth Terapeutics, Veracyte. U. De Giorgi: Financial Interests, Personal, Advisory Board: Janssen, Astellas, MSD, Pfizer, Bayer, Ipsen, Novartis, AstraZeneca, Clovis, PharmaMar, BMS, GSK, Roche; Financial Interests, Institutional, Research Grant: AstraZeneca, Sanofi, Roche. All other authors have declared no conflicts of interest.