1773P - ICECaP-2: Validation of metastasis-free survival (MFS) as a surrogate for overall survival (OS) in localized prostate cancer (LPC) in a more contemporary era

Background

Prior work from ICECaP (Xie et al, JCO 2017; ICECaP-1) showed that MFS is a valid surrogate for OS for patients (pts) with LPC treated predominantly before 2004, when docetaxel became available for metastatic castrate-resistant prostate cancer (mCRPC). We sought to validate this finding in a more contemporary era (ICECaP-2) with greater availability of docetaxel and AR-pathway inhibitors (ARPIs) for mCRPC.

Methods

Eligible trials for ICECaP-2 were those providing individual patient data (IPD) after publication of ICECaP-1 and evaluating adjuvant/salvage therapy for LPC, and which collected MFS and OS data. MFS was defined as distant metastases or death from any cause, and OS defined as death from any cause. Surrogacy was evaluated using a meta-analytic two-stage validation model, with an R² ≥0.7 defined a priori as clinically relevant.

Results

15,164 IPD from 14 trials were included in ICECaP-2. For surrogacy condition 1, Kendall’s tau was 0.92 for MFS with OS at the patient-level, and R² from weighted linear regression (WLR) of 8-yr OS on 5-yr MFS was 0.73 (95% CI 0.53-0.82) at the trial level. For condition 2, R² was 0.83 (0.64-0.89) from WLR of log (HR)-OS on log (HR)-MFS. The surrogate threshold effect on OS was an HR(MFS) of 0.81. Comparisons between ICECaP-1 and ICECaP-2 are shown in the table.

Table: 1773P

Conclusions

MFS remains a valid surrogate for OS in pts with LPC treated in a contemporary era with greater access to docetaxel and ARPIs for mCRPC. Surrogacy effects were similar to those observed in ICECaP-1. This supports the use of MFS as the primary outcome measure for ongoing trials in LPC.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Janssen, Dendreon, Sanofi, Astellas/Pfizer, Bayer, PCF Challenge.

Disclosure

W. Xie: Financial Interests, Personal, Advisory Role: Convergent Therapeutics, Inc. S. Halabi: Financial Interests, Personal, Other, Member of DSMB: Sanofi, Aveo Oncology, BMS, Janssen; Financial Interests, Institutional, Funding: ASCO. N.D. James: Financial Interests, Personal, Advisory Board, Advice around PARP inhibitors: AstraZeneca; Financial Interests, Personal, Advisory Board, Prostate cancer therapies: Janssen, Clovis, Novartis; Financial Interests, Institutional, Advisory Board, Assisted with submissions regarding licensing for abiraterone: Janssen; Financial Interests, Personal, Advisory Board, Docetaxel: Sanofi; Financial Interests, Institutional, Advisory Board, Providing STAMPEDE trial data to facilitate licence extensions internationally for docetaxel: Sanofi; Financial Interests, Personal, Advisory Board, Bladder cancer therapy: Merck; Financial Interests, Personal, Advisory Board, Advice around novel hormone therapies for prostate cancer: Bayer; Financial Interests, Personal, Invited Speaker, Lecture tour in Brazil August 2022 - speaking on therapy for advanced prostate cancer: Merck Sharp & Dohme (UK) Limited; Financial Interests, Institutional, Coordinating PI, Funding for STAMPEDE trial: Janssen, Astellas; Financial Interests, Institutional, Coordinating PI, Funding for RADIO trial bladder cancer: AstraZeneca. K. Fizazi: Financial Interests, Institutional, Advisory Board: Astellas, Bayer, Janssen, AAA, MSD, AstraZeneca, Novartis/AAA, Pfizer, Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker: Astellas, Bayer, Janssen, Sanofi, MSD, AstraZeneca, Novartis, Pfizer; Financial Interests, Personal, Advisory Board: Curevac, Orion; Financial Interests, Personal, Advisory Board, February 2022: Arvinas; Financial Interests, Personal, Advisory Board, April 2022: Macrogenics; Financial Interests, Institutional, Research Grant, Trial chair: Pfizer, Bayer, AstraZeneca, Orion, MSD, BMS, Janssen; Non-Financial Interests, Principal Investigator, Chair of the 7DX phase 3 trial: BMS; Non-Financial Interests, Principal Investigator, Chair of the Docetaxel-pembrolizumab phase 3 trial: Merck; Non-Financial Interests, Principal Investigator, Chair of the Darolutamide BCR phase 3 trial: Bayer; Non-Financial Interests, Principal Investigator, Chair of the PSMAfore phase 3 trial: AAA/Novartis; Non-Financial Interests, Principal Investigator, Chair of the CYPIDES ODM-208 Phase I-II trial: Orion; Non-Financial Interests, Principal Investigator, Chair of the STESIDES ODM-209 Phase I-II trial: Orion; Non-Financial Interests, Principal Investigator, Chair of the CAPITELLO 281 phase 3 trial: AstraZeneca; Non-Financial Interests, Principal Investigator, Chair of the TALAPRO-2 and TALAPRO-3 phase 3 trials: Pfizer; Non-Financial Interests, Principal Investigator, Chair of the RADIANT phase 3 trial: Bayer; Non-Financial Interests, Principal Investigator, Chair of the TRITON-3 phase 3 trial: Clovis. S. Gillessen: Financial Interests, Personal, Advisory Board, 2018: Sanofi, Roche; Financial Interests, Personal, Advisory Board, 2018, 2019: Orion; Financial Interests, Personal, Invited Speaker, 2019 Speaker's Bureau: Janssen Cilag; Financial Interests, Personal, Advisory Board, 2020: Amgen; Financial Interests, Personal, Invited Speaker, 2020: ESMO; Financial Interests, Personal, Other, Travel Grant 2020: ProteoMEdiX; Financial Interests, Institutional, Advisory Board, 2018, 2019, 2022: Bayer; Financial Interests, Institutional, Advisory Board, 2020: Janssen Cilag, Roche, Pfizer; Financial Interests, Institutional, Advisory Board, 2018: AAA International, Menarini Silicon Biosystems; Financial Interests, Institutional, Advisory Board, 2019, 2020: Astellas Pharma; Financial Interests, Institutional, Advisory Board, 2019: Tolero Pharmaceuticals; Financial Interests, Institutional, Advisory Board, 2020, 2022: MSD Merck Sharp & Dohme; Financial Interests, Personal, Invited Speaker, 2021, 2022: SAKK, DESO; Financial Interests, Institutional, Advisory Board, 2021: Telixpharma, BMS, AAA International, Novartis, Modra Pharmaceuticas Holding B.V.; Financial Interests, Institutional, Other, Steering Committee 2021: Amgen; Financial Interests, Institutional, Advisory Board, 2021, 2022: Orion, Bayer; Financial Interests, Personal, Invited Speaker, 2021: SAKK, SAKK, SAMO - IBCSG (Swiss Academy of Multidisciplinary oncology); Financial Interests, Personal, Advisory Board, 2021: MSD Merck Sharp & Dhome; Financial Interests, Personal, Other, 2021: RSI (Televisione Svizzera Italiana); Financial Interests, Institutional, Invited Speaker, 2021, 2022: Silvio Grasso Consulting; Financial Interests, Institutional, Other, Faculty activity 2022: WebMD-Medscape; Financial Interests, Institutional, Advisory Board, 2022: Myriad genetics, AstraZeneca, Amgen; Financial Interests, Institutional, Invited Speaker, 2022: TOLREMO, ESMO; Financial Interests, Personal, Other, Travel support 2022: AstraZeneca; Financial Interests, Institutional, Other, Interview 2022: PeerVoice; Financial Interests, Institutional, Funding, 2021, Unrestricted grant for a Covid related study as co-investigator: Astellas; Non-Financial Interests, Advisory Role, 2019: Menarini Silicon Biosystems, Aranda; Non-Financial Interests, Advisory Role, Continuing: ProteoMediX. N. Mottet: Financial Interests, Personal, Invited Speaker, symposia and educational lectures in various countries inside and outside Europe: Astellas; Financial Interests, Personal, Advisory Board: Astellas, Bayer, Sanofi; Financial Interests, Personal, Invited Speaker, Symposia and multiple educational programs: Janssen; Financial Interests, Personal, Invited Speaker, Symposium: Bayer; Financial Interests, Personal, Invited Speaker, Educational programs: Ipsen, AstraZeneca; Financial Interests, Personal, Invited Speaker, Symposia and educational programs: Sanofi; Financial Interests, Personal, Invited Speaker, lecture on PCa: Riley's lab; Financial Interests, Personal, Other, lectures at educational events: Ismar heal care; Non-Financial Interests, Leadership Role, prostate cancer guideline chair: EAU; Non-Financial Interests, Leadership Role, Prostate Cancer guideline chair: EAU. B. Tombal: Financial Interests, Personal, Advisory Board: Astellas, Bayer, Amgen, Janssen, Sanofi, Myovant, Novartis (AAA), Pfizer, Astellas, MSD, AstraZeneca; Financial Interests, Personal, Invited Speaker: Astellas, Amgen, Ferring; Non-Financial Interests, Member of Board of Directors, Past President: European Organisation of Research and Treatment of Cancer (EORTC); Non-Financial Interests, Member of Board of Directors, Education in the field of Oncology: ISSECAM. C. Sweeney: Financial Interests, Personal, Advisory Board, Consultancy: Genentech_Roche, Bayer, Astellas, Pfizer, Pfizer, Sanofi, Lilly; Financial Interests, Personal, Other, Consultancy: Janssen; Financial Interests, Personal, Advisory Board: Point, Cellcentric; Financial Interests, Personal, Stocks/Shares: Leuchemix; Financial Interests, Institutional, Research Grant: Bayer, Janssen, Astellas, Pfizer, Dendreon, Sanofi. All other authors have declared no conflicts of interest.