TY - JOUR
T1 - Efficacy and safety of prostate radiotherapy in de novo metastatic castration-sensitive prostate cancer (PEACE-1)
T2 - a multicentre, open-label, randomised, phase 3 study with a 2 × 2 factorial design
AU - PEACE-1 investigators
AU - Bossi, Alberto
AU - Foulon, Stéphanie
AU - Maldonado, Xavier
AU - Sargos, Paul
AU - MacDermott, Ray
AU - Kelly, Paul
AU - Fléchon, Aude
AU - Tombal, Bertrand
AU - Supiot, Stephane
AU - Berthold, Dominik
AU - Ronchin, Philippe
AU - Kacso, Gabriel
AU - Salem, Naji
AU - Calabro, Fabio
AU - Berdah, Jean François
AU - Hasbini, Ali
AU - Silva, Marlon
AU - Boustani, Jihane
AU - Ribault, Hélène
AU - Fizazi, Karim
N1 - Publisher Copyright:
© 2024 Elsevier Ltd
PY - 2024/11/23
Y1 - 2024/11/23
N2 - Background: The 2 × 2 PEACE-1 study showed that combining androgen-deprivation therapy with docetaxel and abiraterone improved overall and radiographic progression-free survival in patients with de novo metastatic castration-sensitive prostate cancer. We aimed to examine the efficacy and safety of adding radiotherapy in this population. Methods: We conducted an open-label, randomised, controlled, phase 3 trial with a 2 × 2 factorial design (PEACE-1) at 77 hospitals across Europe. Eligible participants were male patients (aged ≥18 years) with de novo metastatic castration-sensitive prostate cancer confirmed by bone scan, CT, or MRI, and an Eastern Cooperative Oncology Group performance status of 0–1 (or 2 in the case of bone pain). Participants were randomly assigned (1:1:1:1) to standard of care (androgen-deprivation therapy alone or with six cycles of intravenous docetaxel 75 mg/m2 every 3 weeks), standard of care plus abiraterone (oral 1000 mg abiraterone once daily plus oral 5 mg prednisone twice daily), standard of care plus radiotherapy (74 Gy in 37 fractions to the prostate), or standard of care plus radiotherapy and abiraterone. Participants and investigators were not masked to treatment allocation. The coprimary endpoints were radiographic progression-free survival and overall survival, analysed by intention to treat in patients with low-volume metastatic disease and in the overall study population. This ongoing study is registered with EudraCT, 2012-000142-35. Findings: Between Nov 27, 2013, and Dec 20, 2018, 1173 patients were enrolled and 1172 were randomly assigned to receive standard of care (n=296 [25·3%]), standard of care plus abiraterone (n=292 [24·9%]), standard of care plus radiotherapy (n=293 [25·0%]), and standard of care plus abiraterone and radiotherapy (n=291 [24·8%]). Median follow-up was 6·0 years (IQR 5·1–7·0) at the time of radiographic progression-free survival and overall survival analysis. A qualitative interaction between radiotherapy and abiraterone for radiographic progression-free survival in the population of patients with low-volume disease prevented the pooling of intervention groups for analysis (p=0·026). Adding radiotherapy to standard of care improved radiographic progression-free survival in patients with low-volume disease treated with abiraterone (median 4·4 years [99·9% CI 2·5–7·3] in the standard of care plus abiraterone group vs 7·5 years [4·0–not reached] in the standard of care plus abiraterone and radiotherapy group; adjusted hazard ratio [HR] 0·65 [99·9% CI 0·36–1·19]; p=0·019), but not in patients not treated with abiraterone (median 3·0 years [99·9% CI 2·3–4·8] in the standard of care group vs 2·6 years [1·7–4·6] in the standard of care plus radiotherapy group; 1·08 [0·65–1·80]; p=0·61). For overall survival, the predefined threshold for a statistical interaction was not reached (p=0·12); therefore, the two intervention groups receiving radiotherapy were pooled together for analysis. In patients with low-volume disease, the overall survival was not influenced by radiotherapy (median 6·9 years [95·1% CI 5·9–7·5] for standard of care with or without abiraterone vs 7·5 years [6·0–not reached] for standard of care plus radiotherapy with or without abiraterone; HR 0·98 [95·1% CI 0·74–1·28]; p=0·86). In the overall safety population, 339 (56·1%) of 604 patients who did not receive radiotherapy and 329 (58·8%) of 560 patients who received radiotherapy developed at least one severe adverse event (grade ≥3), the most common being hypertension (110 [18·2%] patients in the standard of care with or without abiraterone group and 127 [22·7%] in the standard of care plus radiotherapy with or without abiraterone group) and neutropenia (40 [6·6%] and 29 [5·2%]). Interpretation: Combining radiotherapy with standard of care plus abiraterone improves radiographic progression-free survival and castration resistance-free survival, but not overall survival in patients with low-volume de novo metastatic castration-sensitive prostate cancer. Radiotherapy reduces the occurrence of serious genitourinary events, regardless of metastatic burden and without increasing the overall toxicity, and could become a component of standard of care in patients with both high-volume and low-volume de novo metastatic castration-sensitive prostate cancer. Funding: Janssen-Cilag, Ipsen, Sanofi, and Institut National du Cancer.
AB - Background: The 2 × 2 PEACE-1 study showed that combining androgen-deprivation therapy with docetaxel and abiraterone improved overall and radiographic progression-free survival in patients with de novo metastatic castration-sensitive prostate cancer. We aimed to examine the efficacy and safety of adding radiotherapy in this population. Methods: We conducted an open-label, randomised, controlled, phase 3 trial with a 2 × 2 factorial design (PEACE-1) at 77 hospitals across Europe. Eligible participants were male patients (aged ≥18 years) with de novo metastatic castration-sensitive prostate cancer confirmed by bone scan, CT, or MRI, and an Eastern Cooperative Oncology Group performance status of 0–1 (or 2 in the case of bone pain). Participants were randomly assigned (1:1:1:1) to standard of care (androgen-deprivation therapy alone or with six cycles of intravenous docetaxel 75 mg/m2 every 3 weeks), standard of care plus abiraterone (oral 1000 mg abiraterone once daily plus oral 5 mg prednisone twice daily), standard of care plus radiotherapy (74 Gy in 37 fractions to the prostate), or standard of care plus radiotherapy and abiraterone. Participants and investigators were not masked to treatment allocation. The coprimary endpoints were radiographic progression-free survival and overall survival, analysed by intention to treat in patients with low-volume metastatic disease and in the overall study population. This ongoing study is registered with EudraCT, 2012-000142-35. Findings: Between Nov 27, 2013, and Dec 20, 2018, 1173 patients were enrolled and 1172 were randomly assigned to receive standard of care (n=296 [25·3%]), standard of care plus abiraterone (n=292 [24·9%]), standard of care plus radiotherapy (n=293 [25·0%]), and standard of care plus abiraterone and radiotherapy (n=291 [24·8%]). Median follow-up was 6·0 years (IQR 5·1–7·0) at the time of radiographic progression-free survival and overall survival analysis. A qualitative interaction between radiotherapy and abiraterone for radiographic progression-free survival in the population of patients with low-volume disease prevented the pooling of intervention groups for analysis (p=0·026). Adding radiotherapy to standard of care improved radiographic progression-free survival in patients with low-volume disease treated with abiraterone (median 4·4 years [99·9% CI 2·5–7·3] in the standard of care plus abiraterone group vs 7·5 years [4·0–not reached] in the standard of care plus abiraterone and radiotherapy group; adjusted hazard ratio [HR] 0·65 [99·9% CI 0·36–1·19]; p=0·019), but not in patients not treated with abiraterone (median 3·0 years [99·9% CI 2·3–4·8] in the standard of care group vs 2·6 years [1·7–4·6] in the standard of care plus radiotherapy group; 1·08 [0·65–1·80]; p=0·61). For overall survival, the predefined threshold for a statistical interaction was not reached (p=0·12); therefore, the two intervention groups receiving radiotherapy were pooled together for analysis. In patients with low-volume disease, the overall survival was not influenced by radiotherapy (median 6·9 years [95·1% CI 5·9–7·5] for standard of care with or without abiraterone vs 7·5 years [6·0–not reached] for standard of care plus radiotherapy with or without abiraterone; HR 0·98 [95·1% CI 0·74–1·28]; p=0·86). In the overall safety population, 339 (56·1%) of 604 patients who did not receive radiotherapy and 329 (58·8%) of 560 patients who received radiotherapy developed at least one severe adverse event (grade ≥3), the most common being hypertension (110 [18·2%] patients in the standard of care with or without abiraterone group and 127 [22·7%] in the standard of care plus radiotherapy with or without abiraterone group) and neutropenia (40 [6·6%] and 29 [5·2%]). Interpretation: Combining radiotherapy with standard of care plus abiraterone improves radiographic progression-free survival and castration resistance-free survival, but not overall survival in patients with low-volume de novo metastatic castration-sensitive prostate cancer. Radiotherapy reduces the occurrence of serious genitourinary events, regardless of metastatic burden and without increasing the overall toxicity, and could become a component of standard of care in patients with both high-volume and low-volume de novo metastatic castration-sensitive prostate cancer. Funding: Janssen-Cilag, Ipsen, Sanofi, and Institut National du Cancer.
UR - http://www.scopus.com/inward/record.url?scp=85209396956&partnerID=8YFLogxK
U2 - 10.1016/S0140-6736(24)01865-8
DO - 10.1016/S0140-6736(24)01865-8
M3 - Article
AN - SCOPUS:85209396956
SN - 0140-6736
VL - 404
SP - 2065
EP - 2076
JO - The Lancet
JF - The Lancet
IS - 10467
ER -