1786P - Effect of rapid ultra-low prostate-specific antigen decline (UL PSA) in TITAN patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC) who received apalutamide (APA) plus androgen deprivation therapy (ADT)

Background

In TITAN mCSPC pts, 3 mos’ APA + ADT produced rapid and deep ≤0.2 ng/mL PSA decline that was associated with improved overall survival (OS) (Chowdhury et al, Ann Oncol. 2023). Here we evaluate the effect of UL PSA on outcomes.

Methods

525 and 527 pts receiving 240 mg/d APA or placebo (PBO) + ADT were analyzed. Two groups of UL PSA, >0.02 to ≤0.2 ng/mL (UL1) and ≤0.02 ng/mL (UL2), were assessed for association with OS, radiographic progression-free survival, time to castration resistance, and time to PSA progression using landmark analysis, Kaplan-Meier method, and Cox proportional hazards model.

Results

Of 515 APA and 520 PBO pts with evaluable UL PSA values, 49% and 17%, respectively, achieved UL2 PSA during the study. By 3 mos, UL1 and UL2 were achieved in 38% and 23% of APA and 15% and 5% of PBO pts. By 6 mos, these values were 29% and 36% (APA), and 17% and 6% (PBO). APA pts with UL1/UL2 at 3 mos had lower baseline PSA and higher % of low-volume disease vs PSA>0.2 ng/mL. Pts with UL1/UL2 at 3 or 6 mos had improved long-term outcomes irrespective of volume. Volume-adjusted outcomes were significantly improved in pts with UL1/UL2 achieved at 3 mos (Table) or at 6 mos. At 42 mos’ follow-up post landmark, survival rate (% [95% CI]) was 89 (81-94), 81 (75-85), and 34 (26-43) when UL2 was achieved at 3 mos, after 3 mos, or never after 3 mos and was 89 (83-93), 77 (70-83), and 34 (26-43) when UL2 was achieved at 6 mos, after 6 mos, or never after 6 mos. Survival rate at 42 mos with UL1, UL2, or none achieved at any time was 59 (48-68), 92 (88-95), and 33 (26-41). APA safety profile across subgroups was consistent with previous reports. Table: 1786P

^aStratified by disease volume at baseline.^b44.0 mos follow-up. ^c22.7 mos follow-up.

Conclusions

More TITAN mCSPC pts achieved UL PSA with APA vs PBO. Rapid and deep UL PSA was associated with significantly improved survival outcomes regardless of disease volume, most notably UL2. Data may guide design of future treatment escalation/de-escalation trials in mCSPC.

Clinical trial identification

56021927PCR3002.

Editorial acknowledgement

Writing assistance was provided by Larissa Belova, PhD, of Parexel, and was funded by Janssen Global Services, LLC.

Legal entity responsible for the study

Janssen Research & Development.

Funding

Janssen Research & Development.

Disclosure

A.S. Merseburger: Financial Interests, Advisory Role: Janssen, Astellas, Bayer. N. Agarwal: Financial Interests, Personal, Advisory Board, In the last two calendar years, I participated in the scientific advisory board of these pharma companies between February 2021 to April 2021. None after that: Merck, Aveo, Gilead, Lilly, Exelixis, Foundation Medicine; Financial Interests, Trial Chair, I am involved in the following phase 3 trials as the trial co-chair: TALAPRO-2, TALAPRO-3 (both Pfizer), and CONTACT-2 (Exelxis): Pfizer, Exelixis; Financial Interests, Institutional, Other, I serve in the leadership of my cancer center (Huntsman Cancer Institute, University of Utah. Salt Lake City, UT, USA). There are multiple research projects sponsored by these companies which pay money to my institution: Arnivas, Astellas, AstraZeneca, Bavarian Nordic, Bayer, BMS, Calithera, Celldex, Crispr, Eisai, Eli Lilly, EMD Serono, Exelixis, Genentech, Gilead, GSK, Immunomedics, Janssen, Lava, Medivation, Merck, Nektar, Neoleukin, New Link Genetics, Novartis, Oric, Pfizer, Prometheus, Rexahn, Roche, Sanofi, Seattle Genetics, Takeda, and Tracon.; Financial Interests, Steering Committee Member, I am involved in the steering committee of the trials sponsored by these pharmas with no personal honorarium: AstraZeneca, Calithera, Clovis, Crispr, Eisai, Eli Lilly, Exelixis, Immunomedics, Janssen; Financial Interests, Steering Committee Member, I am involved in the steering committee of the trials sponsored by these pharma companies with no personal honorarium: Merck, Nektar, New Link Genetics, Oric, Pfizer, Prometheus, Rexahn, Takeda, and Tracon. H. Uemura: Financial Interests, Funding, Research Grant: AstraZeneca, Takeda Pharm, Ono Pharm. A. Bhaumik, S.D. Mundle, S.D. Brookman-May, S.A. Mccarthy: Financial Interests, Full or part-time Employment: Janssen Research & Development; Financial Interests, Stocks or ownership: Janssen Research & Development. J. Boehm, N. Tran, N. Krochmann, M. Nematian: Financial Interests, Full or part-time Employment: Janssen Cilag GmbH; Financial Interests, Stocks or ownership: Janssen Cilag GmbH. K.N.N. Chi: Financial Interests, Advisory Role: ESSA, Astellas Pharma, Janssen, Sanofi, Amgen, Bayer, AstraZeneca, Roche, Point Biopharma, Daiichi Sankyo, Merck, Constellation Pharmaceuticals; Financial Interests, Expert Testimony: AstraZeneca, Novartis; Financial Interests, Other, Honoraria: Janssen, Astellas Pharma, Bayer, AstraZeneca, Roche, Merck, POINT Biopharma; Financial Interests, Research Funding: Janssen, Astellas Pharma, Bayer, Sanofi, BMS, Merck, Roche, AstraZeneca, Novartis, Pfizer, ESSA. S. Chowdhury: Financial Interests, Speaker, Consultant, Advisor: Telix, Novartis, Remedy Bio, Curesponse; Financial Interests, Speaker’s Bureau, Honoraria: Janssen, Astellas; Financial Interests, Advisory Board: Janssen, Amgen, Novartis; Financial Interests, Stocks/Shares: Curesponse, Remedy Bio. All other authors have declared no conflicts of interest.