PEACE-3 / EORTC-1333 Trial

[Slide 1] Background Abiraterone and enzalutamide are standard of care options for 1st line treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) progressing on androgen deprivation therapy (ADT) (1,2) No combination so far has been proven to increase radiological progression-free survival (rPFS) and overall survival (OS) in first line mCRPC Radium-223 dichloride (Ra223) is an alpha particle-emitting calcium mimetic that selectively targets bone metastases and induces double-stranded DNA-breaks(3) In the ALSYMPCA trial, Ra223 has been shown to increase OS (HR: 0.7), in an era before the introduction of abiraterone and enzalutamide(4) The ERA-223 trial tested the combination of abiraterone plus Ra223 versus abiraterone plus placebo. The combination did not show a benefit in symptomatic skeletal event-free survival or OS and was associated with an increase in fractures(5) (1) Ryan CJ et al. N Engl J Med 2013; (2) Beer TM et al N Engl J Med 2014; (3) Morris MJ et al. Nat Rev Urol 2019; (4) Parker C et al. N Engl J Med 2013; (5) Smith M et al. Lancet Oncol 2019 BARCELONA congress 2024 ESMO --- [Slide 2] EORTC-GUCG 1333 (PEACE-3) Ra223 Study population 55 kBq/kg iv every 4 weeks for 6 cycles plus Primary endpoint Patients with mCRPC rPFS and bone metastases N=446** Enzalutamide 160 mg od Asymptomatic or Key secondary mildly symptomatic* Stratification factors endpoints WHO PS of 0 or 1 Country Safety 1:1 No prior treatment Baseline pain (BPI worst pain 0-1 vs 2-3) Randomisation Overall Survival with enzalutamide or Prior docetaxel (yes vs no) Use of bone protecting agents Time to next treatment Ra223 Prior abiraterone (yes vs no) Time to pain progression No known visceral Time to first SSE metastases (symptomatic skeletal Ongoing ADT Enzalutamide 160 mg od event) "defined as brief pain inventory WP24 score <4 " original target accrual N=560, adapted for slow accrual Use of bone protecting agents (BPA) made mandatory BARCELONA congress 2024 ESMO (after inclusion of 119 patients) --- [Slide 3] Overall Survival at interim analysis (80% of OS events) Arm n/N Median (95%CI) 100 90 Enzalutamide 110/222 Ra223 42.3 (36.8-49.1) mo 80 Enzalutamide + Ra223 70 Enzalutamide 129/224 35.0 (28.8-38.9) mo Overall Survival (%) 60 HR (95%CI) 0.69 (0.52-0.90) 50 40 Enzalutamide Log-Rank p- 0.0031 <0.0034 value 30 20 Pre-set level of significance for interim analysis 10 was s 0.0034 Due to non-proportional hazards plus lack of 0 unequivocal significance for RMST (restricted 0 6 12 18 24 30 36 42 48 54 60 66 72 mean survival time) sensitivity analysis, study will Time in months continue to final OS analysis Patients-at-Risk (No. Cumulative Events) Enza- 224(0) 206 (15) 107 (64) 58 (90) 30 (112) 14 (123) 1 (129) Enza+Ra223- 222(0) 194 (21) 114(53) 71 (73) 43(90) 23 (101) 12 (105) BARCELONA congress 2024 ESMO --- [Slide 4] Conclusions Combination of enzalutamide and 6 cycles of Ra223 shows a statistically significant improvement in rPFS HR of 0.69 (p=0.0009) Median rPFS increased from 16.4 months with enzalutamide to 19.4 months with the combination Improvement in rPFS supported by a significantly improved OS (HR 0.69, p=0.0031) Due to non-proportional hazards this will be tested further in the final OS analysis to confirm and further characterise the result Improvement in rPFS is also supported by a statistically significant improvement in time to next systemic treatment (HR 0.57, p<0.0001) Drug related ≥ grade 3 adverse events increased from 19% to 28% in the combination arm

[Slide 1] 16:30 - 18:15 Presidential Symposium I: Practice-changing trials CHAIRS: ANDRES CERVANTES, KARIN JORDAN Primary endpoint: rPFS 100 90 Arm n/N Median (95%CI) 80 Enzalutamide + Ra223 Enzalutamide + Ra223 139/222 19.4 (17.1-25.3) mo Radiological Progression Free Survival (%) 70 Enzalutamide 160/224 16.4 (13.8-19.2) mo 60 congress 24mo rPFS: 50 36% vs. 45% HR (95%CI) 0.69 (0.54-0.87) Log-Rank p-value 0.0009 40 Silke Gillessen 30 Assumption of proportional hazard achieved Enzalutamide A randomized multicenter open label phase . trial comparing 20 enzalutamide vs a combination of Radium-223 (Ra223) and 10 enzalutamide in asymptomatic or mildly symptomatic patients with bone metastatic clastration-resistant prostate 0 0 6 12 18 24 30 36 42 48 54 60 66 72 cancer (mCRPC) First Time in months Patients-at-Risk (No. Cumulative Events) Enza- 224(0) 122(84) 52 (128) 13(150) 7(155) 3 (158) 0 (160) Enza+Ra223- 222(0) 138(65) 64 (107) 32(123) 19(131) 9(135) 3 (137) BARCELONIA congress ESMO BARCELONA congress 2024 ESMO Barcelona Auditorium - Hall 2 BARCELONA SPAIN 13-17 SEPTEMBER 2024 --- [Slide 2] 16:30 18:15 Presidential Symposium I: Practice-changing trials CHAIRS: ANDRES CERVANTES, KARIN JORDAN Overall Survival at interim analysis (80% of os events) Arm n/N Median (95%CI) 100 Enzalutamide 90 110/222 42.3 (36.8-49.1) mo + Ra223 80 Enzalutamide + Ra223 70 Enzalutamide 129/224 35.0 (28.8-38.9) mo Overall Survival (%) ESMO 60 HR (95%CI) 0.69 (0.52-0.90) 50 40 Enzalutamide Log-Rank 0.0031 <0.0034 Silke Gillessen value 30 A randomized multicenter open label phase a trial comparing 20 Pre-set level of significance for interim analysis enzalutamide vs a combination of Radium-223 Ra223) and was S 0.0034 10 enzalutamide in asymptomatic or midly symptomatic Due to non-proportional hazards plus lack of patients with bone metastatic clastration-resistant prostate 0 unequivocal significance for RMST (restricted 0 6 12 18 24 30 36 42 48 54 60 66 72 cancer (mCRPC) First mean survival time) sensitivity analysis, study will Time in months continue to final OS analysis Patients-at-Risk (No. Cumulative Events) Enza- 224(0) 206(15) 107(64) 58(90) 30 (112) 14 (123) 1 (129) Enza+Ra223. 222(0) 194(21) 114(53) 71(73) 43(90) 23 (101) 12 (105) BARCELONA congress ESMO BARCELONA congress LIVE 2024 ESMO Barcelona Auditorium - Hall 2 BARCELONA SPAIN 13-17 SEPTEMBER 2024 + --- [Slide 3] 16:30 - 18:15 Presidential Symposium I: Practice-changing trials CHAIRS ANDRES CERVANTES, KARIN JORDAN EORTC-GUCG 1333 (PEACE-3) Ra223 Study population 55 kBq/kg iv every 4 weeks Patients with mCRPC for 6 cycles plus Primary endpoint rPFS and bone metastases N=446** Enzalutamide 160 mg od Asymptomatic or Key secondary ESMO mildly symptomatic* Stratification factors endpoints WHO PS of 0 or 1 Country Safety 1:1 No prior treatment Baseline pain (BPI worst pain 0-1 vs 2-3) Randomisation Overall Survival Silke Gillessen with enzalutamide or Prior docetaxel (yes vs no) Use of bone protecting agents Time to next treatment Ra223 A randomized multicenter open label phase a trial comparing Prior abiraterone (yes vs no) Time to pain progression No known visceral Time to first SSE enzalutamide vs a combination of Radium-223 Ra223) and metastases (symptomatic skeletal enzalutamide in asymptomatic or midly symptomatic Ongoing ADT Enzalutamide 160 mg od event) patients with bone metastatic castration-resistant prostate cancer (mCRPC) First "defined as brief pain inventory WP24 score < 4 ** original target accrual N=560, adapted for slow accrual congress ESMO BARCELONA congress 2024 ESMO Barcelona Auditorium - Hall 2 BARCELONA SPAIN 13-17 SEPTEMBER 2024 --- [Slide 4] 16:30 - 18:15 Presidential Symposium I: Practice-changing trials CHAIRS: ANDRES CERVANTES, KARIN JORDAN Conclusion: Radium-223 after PEACE-3 Combining Enzalutamide and Radium-223 improves rPFS (HR 0.69) and probably also OS (HR 0.69) in (mostly ARPI-naive) mCRPC and predominant bone metastases ESMO If this combination is used, a Bone-Protecting Agent is mandatory (mostly Denosumab) Karim Fizazi Baseline symptomatic bone disease is not needed to benefit from Enza+Ra-223 ! Invited Discussant LBA1 Blood pressure should be monitored when using Enzalutamide (+/- Radium-223) More data needed in PEACE-3 (ONJ, QoL, long-term OS, etc) With more Radium-223 phase 3 trials maturing, we'll need to optimize the use of Radium-223 VS Lu-PSMA (and hopefully soon other radio-pharmaceuticals) BARCELONA congress 2024 ESMO Barcelona Auditorium - Hall 2 BARCELONA SPAIN 13-17 SEPTEMBER 2024

[Slide 1] EORTC-GUCG 1333 (PEACE-3) Ra223 Study population 55 kBq/kg iv every 4 weeks for 6 cycles plus Primary endpoint Patients with mCRPC rPFS and bone metastases N=446** Enzalutamide 160 mg od Asymptomatic or Key secondary mildly symptomatic* Stratification factors endpoints WHO PS of 0 or 1 Country Safety 1:1 No prior treatment Baseline pain (BPI worst pain 0-1 VS 2-3) Randomisation Overall Survival with enzalutamide or Prior docetaxel (yes VS no) Use of bone protecting agents Time to next treatment Ra223 Prior abiraterone (yes VS no) Time to pain progression No known visceral Time to first SSE metastases (symptomatic skeletal Ongoing ADT Enzalutamide 160 mg od event) *defined as brief pain inventory WP24 score < 4 ** original target accrual N=560, adapted for slow accrual BARCELONA congress 2024 ESMO Baseline characteristics 446 patients enrolled in 12 countries, 11/2015 to 03/2023, median follow-up: 42.2 months Enza+Ra223 Enza (N=222) (N=224) N (%) N (%) Age, Median (range) years 70.0 (43.0 90.0) 70.0 (47.0 90.0) PSA, Median (Q25-Q75) ng/mL 25.3 (6.5 68.8) 23.0 (8.5 54.9) WHO Performance status 0 152 (69) 154 (69) Prior docetaxel(1) 67 (30.2) 66 (30) Prior abiraterone¹ 4 (2) 7 (3) Bone lesions² <10 109 (49) 105 (47) ≥10 93 (42) 99 (44) Missing or diffuse lesions 20 (9) 20 (9) Alkaline phosphatase <ULN 127 (57) 107 (48) >ULN 82 (37) 110 (49) Missing 13 (6) 7 (3) Extra-skeletal disease at baseline 77 (35) 73 (33) (1) Prior docetaxel or abiraterone was allowed for mHSPC (2) Per imaging guidelines, the type of bone lesions is reported by a radiologist and classified into focal, diffuse or equivocal. Only focal bone lesions can be counted. BARCELONA congress 2024 ESMO --- [Slide 2] Primary endpoint: rPFS 100 90 Arm n/N Median (95%CI) 80 Enzalutamide + Ra223 Enzalutamide + Ra223 139/222 19.4 (17.1-25.3) mo Radiological Progression Free Survival (%) 70 Enzalutamide 160/224 16.4 (13.8-19.2) mo 60 24mo rPFS: 36% VS. 45% HR (95%CI) 0.69 (0.54-0.87) 50 Log-Rank p-value 0.0009 40 30 Assumption of proportional hazard achieved Enzalutamide 20 10 0 0 6 12 18 24 30 36 42 48 54 60 66 72 Time in months Patients-at-Risk (No. Cumulative Events) Enza- 224 (0) 122 (84) 52 (128) 13 (150) 7 (155) 3 (158) 0 (160) Enza+Ra223- 222 (0) 138 (65) 64 (107) 32 (123) 19 (131) 9 (135) 3 (137) BARCELONA congress ESMO Overall Survival at interim analysis (80% of OS events) Arm n/N Median (95%CI) 100 Enzalutamide 90 110/222 42.3 (36.8-49.1) mo + Ra223 80 Enzalutamide + Ra223 70 Enzalutamide 129/224 35.0 (28.8-38.9) mo Overall Survival (%) 60 HR (95%CI) 0.69 (0.52-0.90) 50 40 Enzalutamide Log-Rank p- 0.0031 <0.0034 value 30 20 Pre-set level of significance for interim analysis was < 0.0034 10 Due to non-proportional hazards plus lack of 0 unequivocal significance for RMST (restricted 0 6 12 18 24 30 36 42 48 54 60 66 72 mean survival time) sensitivity analysis, study will Time in months continue to final OS analysis Patients-at-Risk (No. Cumulative Events) Enza- 224 (0) 206 (15) 107 (64) 58 (90) 30 (112) 14 (123) 1 (129) Enza+Ra223- 222 (0) 194 (21) 114 (53) 71 (73) 43 (90) 23 (101) 12 (105) BARCELONA 2024 ESMO congress --- [Slide 3] Time to symptomatic skeletal event 100 Enza+Ra223 Enza Estimate of 90 proportion with a (N=222) (N=224) SSE Time to symptomatic skeletal event (cumulative % 80 % (95% CI) 70 At 24 months 17.8 (12.9 23.4) 18.0 (13.2 - 23.4) 60 Enza+Ra223 Enza 50 BPA use during (N=222) (N=224) 40 treatment 24mo TTSSE: Enzalutamide N (%) 30 18% VS. 18% No (or after fracture) 41 (18.5) 35 (15.6) 20 Yes 181 (81.5) 189 (84.4) 10 Enzalutamide + Ra223 0 0 6 12 18 24 30 36 42 48 54 60 66 72 Time in months Hazard No formal comparison Patients-at-Risk (No. Cumulative Events) ratio as previous endpoint Enza- 224 (0) 126 (30) 46 (39) 14 (46) 5 (47) 1 (47) 0 (47) 0.93 (0.62 1.38) was not significant nza+Ra223- 222 (0) 141 (23) 60 (37) 29 (43) 18 (43) 8 (44) 3 (44) --- [Slide 4] Safety Enza+Ra223 Enza (N=218) (N=224) Patients N (%) N (%) Adverse events (AEs) 218 (100) 216 (96) Drug-related AEs 183 (84) 158 (71) Serious AEs 93 (43) 66 (30) Serious drug-related AEs 18 (8) 3 (1) Grade 3-5 AEs 143 (66) 125 (56) Grade 3-5 drug-related AEs 61 (28) 42 (19) Death due to AE 7 (3) 4 (2) Death due to a drug-related AE 0 0 Treatment discontinuation due to toxicity Enzalutamide 13 (8) 12 (7) RA223 7 (3) BARCELONA 2024 ESMOCongress Safety (2) Most common grade 3-5 Enza+Ra223 Enza treatment emergent AE (TEAE) (N=218) (N=224) N (%) N (%) All Hypertension 73 (33.5) 77 (34.4) Fatigue 12 (5.5) 4 (1.8) Fracture 11 (5.1) 3 (1.3) Anaemia 10 (4.6) 5 (2.2) Neutropenia 10 (4.6) 0 Bone Pain 9 (4.1) 11 (4.9) Weight Decreased 7 (3.2) 1 (0.4) Spinal Cord Compression 6 (2.8) 8 (3.6) Treatment related Hypertension 25 (11.5) 27 (12.1) Fatigue 9 (4.1) 3 (1.3) Anaemia 6 (2.8) 0 Neutropenia 7 (3.2) 0 Side effects of special interest: 1 MDS, 1 AML and 1 CML in the combination arm BARCELONA 2024 ESMO congress

[Slide 1] 4 Methods — Study design Statistical design Primary analysis: 283 rPFS event Enzalutamide 160 mg od Study population + Key secondary endpoints Primary endpoint Patients with mCRPC Ra223 55 kBq/kg iv rPFS tested semi-hierarchically. and bone metastases N=446** every 4 weeks for 6 cycles OS tested at 1-sided Asymptomatic or Key secondary mildly symptomatic* Overall Survival a = 0.0034 due to interim Stratification factors WHO PS of 0 or 1 1:1 Country Time to next treatment testing (239 events). No prior treatment Randomisation Baseline pain (BPI worst pain 0-1 vs 2-3) Time to pain progression with enzalutamide or Prior docetaxel (yes vs no) Time to first SSE Use of bone protecting agents Ra223 Prior abiraterone (yes vs no) (symptomatic skeletal Final OS analysis: No known visceral event) 317 OS events metastases Safety Ongoing ADT Enzalutamide 160 mg od Treatment emergent (target = 299) CTCAE OS tested at 1-sided *defined as brief pain inventory WP24 score < 4 a = 0.0248 ** original target accrual N=560, adapted for slow accrual 70% power to detect IDMC recommendation (Sep 2024): HR=0.75 Use of bone protecting agents (BPA) made mandatory OS at primary analysis considered (March 2018 after inclusion of 119 patients) significant but conducts a final OS OS tested on the ITT set (ie all randomized patients) - stratified for baseline pain, prior analysis to confirm the magnitude of docetaxel and use of BPA. benefit. ASCO Genitourinary #GU26 PRESENTED BY. Enrique Gallardo, MD ASCO AMERICAN SOCIETY OF CONICAL Cancers Symposium Presentation a emperty of the author and ANCO required for muse; contact permissions@sco.org KNOWLEDGE CONQUERS CANCER --- [Slide 2] 7 Final OS results Event/ Median (95%CI) Hazard Ratio 1-sided P- Total (months) (95% CI)2 value 100 Treatment Treatment Enza Logrank: Enza+RAD223 90 32.62 0.0096³ Enza 165/224 (29.31-38.24) 0.76 80 Permutation: 38.21 (0.60-0.96) Enza+Ra223 152/222 0.0105 (33.08-44.75) 70 Kaplan-Meier method: 2Cox model; 3 Stratified Logrank test 60 Overall survival (%) Enza+Ra223 Enza 50 (N=222) (N=224) 40 (95% CI) (95% CI) 6 mths 96.8 (93.5-98.5%) 99.1 (96.5-99.8%) 30 12 mths 90.5 (85.9-93.7%) 92.9 (88.6-95.6%) 20 18 mths 81.1 (75.3-85.6%) 80.8 (74.9-85.3%) 24 mths 10 71.1 (64.7-76.6%) 67.7 (61.2-73.4%) 36 mths 54.2 (47.1-60.6%) 47.4 (40.6-54.0%) 0 0 6 12 18 24 30 36 42 48 54 60 66 72 78 84 90 96 102 108 Time in months Preset level of significance at final analysis: <0.0248 Patients-at-Risk Enza- 224 209 151 84 35 20 6 3 0 Crossing of the curves (still) present at month 18 Enza+RAD223- 222 201 156 94 53 32 20 9 2 0 Only 3 patients censored < 24 months Database locked on 12 January 2026 (cut off date: 01 May 2025) ASCO Genitourinary #GU26 PRESENTED BY: Enrique Gallardo, MD ASCO AMERICAN SOCIETY OF CLINICAL ONCULOGY Cancers Symposium Presentation & property or the author and ASCO Parmission required for muse contact KNOWLEDGE CONQUERS CANCER --- [Slide 3] Safety Summary: TEAE grade ≥3 Enza+RAD223 Enza Nbr of patients (%) with grade 3-5 (N=218) (N=224) TEAE Side effects of special interest: N (%) N (%) 1 MDS All 151 (69.3%) 129 (57.6%) 1 AML Hypertension 78 (35.8) 80 (35.7) 1 CML (drug-related) Fatigue 12 (5.5) 4 (1.8) All 3 in the combination arm Fracture 12 (5.5) 3 (1.3) 17 osteonecrosis of the jaw: Anemia 13 (6) 5 (2.2) 14 in the combo (5 grade 3) Neutropenia 10 (4.6) 0 3 in the enza arm Bone pain 13 (6) 12 (5.4) Weight decreased 10 (4.6) 2 (0.9) Spinal cord comprssn 7 (3.2) 8 (3.6) No individual TEAE ≥ grade 3 has increased Drug-related 63 (28.9%) 42 (18.8%) by more than 5% in the combination compared to the enzalutamide alone arm. Hypertension 26 (11.9) 27 (12.1) Fatigue 9 (4.1) 3 (1.3) Anemia Treatment-emergent AEs are all AEs arising from start of 6 (2.8) 0 treatment until 28 days after last dose of any study drug Neutropenia 7 (3.2) 0 ASCO Genitourinary #GU26 PRESENTED BY: Enrique Gallardo, MD ASCO AMEXCAN SOCIETY OF CUNICAL DSCULOGY Cancers Symposium Presentation & property of the author and AHCC Premission required for rouse contact KNOWLEDGE CONQUERS CANCER --- [Slide 4] Event/ Median Hazard Ratio Updated rPFS analysis Total (95%CI) (months) (95% CI)2 Treatment 100 Treatment Enza Enza+RAD223 16.43 90 Enza 176/224 Reference (13.77-19.15) 80 19.19 0.71 Enza+Ra223 156/222 (16.92-24.57) (0.57-0.89) 70 Radiological progression free survival (%) 'Kaplan-Meier method; 2Cox model; 60 50 Enza+RAD223 Enza (N=222) (N=224) 40 (95% CI) (95% CI) 30 6 months 88.4 (83.3-92.0%) 84.6 (79.1-88.8%) 20 12 months 68.9 (62.2-74.7%) 60.6 (53.8-66.8%) 10 18 months 52.9 (45.9-59.4%) 44.5 (37.7-51.0%) 0 24 months 44.1 (37.2-50.7%) 37.2 (30.7-43.7%) 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 72 75 78 81 84 87 90 Time in months Patients-at-Risk Enza- 224 129 74 26 10 4 1 1 rPFS results confirmed with longer follow-up and Enza+RAD223- 222 144 88 45 22 12 6 1 appear little changed from primary analysis. Database locked on 12 January 2026 (cut off date: 01 May 2025) ASCO Genitourinary #GU26 PRESENTED BY: Enrique Gallardo, MD ASCO AMERICAN SOCIETY OF CUNICAL ONCOLOGY Cancers Symposium Presentation & property of the author and ASCO Parmission required for ISSUED contact KNOWLEDGE CONQUERS CANCER

[Slide 1] congress BARCELONA 2024 ESMO 3- PEACE-3: Safety data review The ERA-223 Phase 3 trial Fractures N-806 Study population 56 k5g/hg every for cycles The risk of fractures was strongly reduced MORPC factors " or midy I Randomisation by BPA in PEACE-3 for UA) 90 I go and Matching placebo NO Clear excess of fractures ENZA+Ra-223 (no BPA) in the Abiraterone + Radium-223 combination arm! ENZA (no BPA) AAP - 3 - . I a 4 : : , 1 No this 1235 5533 **** SSYS **** **** **** ***Y : ***1 Smith M, ESMO 2018 and Smith M, Lancet Oncol 2019 Gillessen S, ASCO 2021 --- [Slide 2] BARCELONA 2024 ESMOCongress 3- PEACE-3: Safety data review Most common grade 3-5 Enza+Ra223 Enza treatment emergent AE (N=218) (N=224) N (%) N (%) All Hypertension 73 (33.5) 77 (34.4) Fatigue 12 (5.5) 4 (1.8) Fracture 11 (5.1) 3 (1.3) Anaemia 10 (4.6) 5 (2.2) Neutropenia 10 (4.6) 0 Overall combination was well tolerated But! - High incidence of HTA in patients receiving Enzalutamide (>30%) --- [Slide 3] BARCELONA congress 2024 ESMO 4- PEACE-3: Is this practice changing? The concept of « rPFS + » ... Overall Survival? 100 Arm n/N Median (95%CI) 90 Enzalutamide 110/224 60 + Ra223 42.3 (36.8-49.1) mo 70 Enzalutamide + Ra223 Enzalutamide 129/220 35.0 (28.8-38.9) mo 60 Overall Survival (%) 50 HR (95%CI) 0.69 (0.52-0.90) 40 Enzalutamide 30 20 10 0 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 06 " 72 Time in months Patients-at-Risk Enta- 224 222 206 152 107 77 54 40 30 20 14 6 1 Enza+RAD23- 222 214 194 149 114 92 71 $7 43 36 23 18 12 --- [Slide 4] BARCELONA 2024 ESMOCongress Conclusion: Radium-223 after PEACE-3 Combining Enzalutamide and Radium-223 improves rPFS (HR 0.69) and probably also OS (HR 0.69) in (mostly ARPI-naive) mCRPC and predominant bone metastases If this combination is used, a Bone-Protecting Agent is mandatory (mostly Denosumab) Baseline symptomatic bone disease is not needed to benefit from Enza+Ra-223 ! Blood pressure should be monitored when using Enzalutamide (+/- Radium-223) More data needed in PEACE-3 (ONJ, QoL, long-term OS, etc) With more Radium-223 phase 3 trials maturing, we'll need to optimize the use of Radium-223 VS Lu-PSMA (and hopefully soon other radio-pharmaceuticals)