The PSMAddition Trial Showed Longer Life Without Progression Is Possible With PLUVICTO. That's Victory.

Primary end point

PSMAddition: A study of PLUVICTO in mAPMN/S PC (mHSPC)

rPFS: In the primary analysis, PLUVICTO + ARPI significantly decreased the risk of radiographic progression or death vs ARPI¹

• Median rPFS was not reached in either arm (HR=0.72 [95% CI, 0.58-0.90; P=0.002)¹

In the final analysis
PLUVICTO + ARPI reduced the risk of radiographic progression or death²

• Median rPFS was not reached in the PLUVICTO + ARPI arm vs 48.5 months (95% CI, 40.5-NE) in the ARPI arm

RADIOGRAPHIC PROGRESSION-FREE SURVIVAL

• Final rPFS analysis was performed with a median follow-up period of 37.7 months vs the primary analysis at 23.6 months. This analysis was not controlled for Type-I error^2,3

rPFS benefit was consistent across subgroups^2,*

ECOG, Eastern Cooperative Oncology Group Performance Status; HR, hazard ratio; LDH, lactate dehydrogenase; mAPMN/S PC, metastatic androgen pathway modulation-naive or -sensitive prostate cancer; mHSPC, metastatic hormone-sensitive prostate cancer; NE, not estimable; PSA, prostate-specific antigen; rPFS, radiographic progression-free survival.

*Subgroup analyses are exploratory and not powered for statistical significance.
^aNot a prespecified patient population and analyzed separately from other subgroup data. De novo included stage IVb at diagnosis. Recurrent included stages IVa, IV, and below IV at diagnosis.³

Key secondary end point

Overall survival (OS) analysis in the PSMAddition trial

OS: Numerically favored PLUVICTO

• OS data were still maturing, and statistical significance was not reached at interim analysis 2 (IA2)

• HR was 0.84 (95% CI, 0.63-1.13) at IA1 (median follow-up of 23.6 months)^3,†

• HR decreased to 0.80 (95% CI, 0.63-1.01) at IA2 (median follow-up of 37.7 months)^2,‡

• Median OS was not reached in either arm^2,3

OVERALL SURVIVAL^2,a

IA1, interim analysis 1.
^†Data cutoff for IA1 was January 13, 2025, with a total of 184 events occurring across both study arms; 16% of patients randomized to the ARPI arm subsequently crossed over to receive PLUVICTO following confirmed radiographic progression.^3
‡Data cutoff for IA2 was March 17, 2026, with a total of 291 events occurring across both study arms. Data are from an unadjusted OS analysis that did not account for crossover. 21% of patients randomized to the ARPI arm subsequently crossed over to receive PLUVICTO following confirmed radiographic progression.^2
aData are from IA2.

Additional End Points

Nearly 9 out of 10 patients treated with PLUVICTO + ARPI achieved undetectable PSA^2,*

PSA nadir <0.2 ng/mL at 48 weeks²:

*PSA nadir (<0.2 ng/mL).
^†Not powered for statistical significance.

6 in 10 patients achieved complete responses with PLUVICTO + ARPI^†

In the final analysis

ORR (CR + PR): Higher ORR achieved with PLUVICTO + ARPI vs ARPI^2,‡

Responses are based on soft tissue and bone lesion assessment.
^†Not powered for statistical significance.
^‡By BICR per PCWG3-modified RECIST v1.1 criteria.

• Median DOR was not reached with PLUVICTO + ARPI (95% CI, NR-NR) vs 42.55 with ARPI (95% CI, 33.12-NR)⁴

BICR, Blinded Independent Central Review; PCWG3, Prostate Cancer Working Group 3; RECIST, Response Evaluation Criteria in Solid Tumors.
Overall response rate (ORR) is the percentage of patients who had a complete response (CR) or partial response (PR) at any point after the start of the study treatment until the end of treatment.⁵
CR is the disappearance of all target lesions. Any pathological lymph nodes (target or nontarget) must have reduction in short axis to <10 mm.⁵
PR is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.⁵

60% risk reduction in time to PSA progression with PLUVICTO + ARPI vs ARPI^2,†

Time to PSA progression: Median time to PSA progression was not reached with PLUVICTO + ARPI (NE-NE) vs not reached with ARPI (NE-NE)²

TIME TO PSA PROGRESSION²

^†Not powered for statistical significance.

Progression to mAPMR PC (mCRPC) was delayed for longer with PLUVICTO + ARPI vs ARPI^2,†

Time to castration resistance: Median time to castration resistance was 47.9 months with PLUVICTO + ARPI (40.9-NE) vs 29.6 months with ARPI (25.3-36.6)^2,‡

TIME TO CASTRATION RESISTANCE²

mAPMR PC, metastatic androgen pathway modulation-resistant prostate cancer; mCRPC, metastatic castration-resistant prostate cancer.
^†Not powered for statistical significance.
^‡Time to castration resistance (TTCR) events included rise in serum PSA levels, progression of pre-existing disease, and appearance of new metastases.³

Patient-Reported Outcomes

Final analysis: Median time to worsening of HRQOL⁴

Longitudinal assessment in change from baseline⁴

FACT-P TOTAL SCORE

• The FACT-P total score is the sum of the scores of 39 items of the questionnaire and ranges from 1 to 156, with higher scores indicating better quality of life. FACT-P measures physical well-being, social/family well-being, emotional well-being, functional well-being, and prostate cancer subscale⁶

• Time to worsening of FACT-P total score was a prespecified, nonpowered, secondary exploratory end point and not statistically significant

• PRO questionnaires were collected every 6 weeks through week 36, then every 12 weeks thereafter⁴

• Longitudinal analyses are descriptive, based purely on patient questionnaire responses, and include all available assessments; post-progression questionnaires may continue to be collected

• 85.6% of patients received all 6 doses of PLUVICTO³

Final analysis: Median time to worsening of HRQOL⁴

Longitudinal assessment in change from baseline⁴

BPI-SF PAIN INTENSITY

• BPI-SF assessed the severity of patients' pain and its impact on daily function through a 13-question form, with scores ranging from 0 to 10 and lower scores representing lower levels of pain intensity. BPI-SF measures pain intensity (worst, least, average, current), pain relief, and interference of pain⁶

• Time to worsening of BPI-SF was a prespecified, nonpowered, secondary exploratory end point and not statistically significant

• PRO questionnaires were collected every 6 weeks through week 36, then every 12 weeks thereafter⁴

• Longitudinal analyses are descriptive, based purely on patient questionnaire responses, and include all available assessments; post-progression questionnaires may continue to be collected

• 85.6% of patients received all 6 doses of PLUVICTO³

BPI-SF, Brief Pain Inventory—Short Form; FACT-P, Functional Assessment of Cancer Therapy—Prostate; HRQOL, health-related quality of life; LS, least squares; PRO, patient-reported outcome.

Trial Design

PSMAddition: FIRST POSITIVE TRIAL vs ARPI IN THE MAJORITY OF PATIENTS WITH mHSPC¹

THIS RANDOMIZED, MULTICENTER, OPEN-LABEL, ACTIVE-CONTROLLED STUDY COMPARED PLUVICTO + ARPI vs ARPI¹

Primary end point: rPFS^1,3
Key secondary end point: OS^1,3
Select additional end points: Undetectable PSA,† ORR, time to PSA progression, time to castration resistance^1,3

• In both arms, patients received treatment with abiraterone (n=424), apalutamide (n=372), enzalutamide (n=250), darolutamide (n=68), or another ARPI (n=12)¹

• Patients received a gonadotropin-releasing hormone (GnRH) agonist or antagonist concurrently or had a bilateral orchiectomy¹

• Patients in the ARPI arm were permitted to cross over to receive PLUVICTO upon centrally reviewed radiographic progression³

• After discontinuing PLUVICTO + ARPI, patients (n=173) went on to receive subsequent therapy–76.3% received hormonal therapy, 49.7% received chemotherapy, 11.5% received targeted therapy, and 5.2% received biologic therapy⁴

PSMA+, prostate-specific membrane antigen positive.
*No systemic treatment was allowed, apart from ADT in the neo-/adjuvant setting and/or up to 45 days of ADT, ARPI, or both in the metastatic setting prior to consent.^1
†PSA nadir (<0.2 ng/mL).

PSMAddition evaluated a broad patient population reflective of clinical practice^1,3

PSMAddition enrolled 1144 patients with PSMA+ mHSPC¹

• De novo and recurrent were determined based on stage at initial diagnosis (AJCC Cancer Staging Manual 8th edition)³:
  - De novo: Stage IVb
  - Recurrent: Stage <IV, IV, and IVa

^aHigh tumor volume was defined as visceral metastases and/or ≥4 bone lesions with ≥1 lesion beyond the vertebral bodies and pelvis.^3
bDe novo included stage IVb (52.1% PLUVICTO + ARPI and 47.9% ARPI).^3
cRecurrent included stage IVa (3% PLUVICTO + ARPI and 2.6% ARPI), stage IV (20.6% PLUVICTO + ARPI and 22.7% ARPI) and stages below IV (19.9% PLUVICTO + ARPI and 22.6% ARPI).³