Genitourinary Cancer

SS 41 - GU 5 - Discoveries for High Risk and Recurrent Prostate Cancer

303 - Timing of Androgen Deprivation Therapy for Prostate Cancer Patients After Radiation: Planned Combined Analysis of Two Randomized Phase 3 Trials

Wednesday, October 24
2:30 PM - 2:40 PM
Location: Room 214 A/B

Timing of Androgen Deprivation Therapy for Prostate Cancer Patients After Radiation: Planned Combined Analysis of Two Randomized Phase 3 Trials
D. A. Loblaw1, J. Bassett2, C. D'Este3, G. Pond4, P. Cheung5, M. Frydenberg6, M. T. King7, H. Lukka8, S. Malone9, J. L. Millar10, R. L. Milne11, T. Pickles12, R. Smith11, M. R. Stockler7, S. Turner13, K. H. Tai14, H. Woo15, and G. Duchesne14; 1Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada, 2Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia, 3NCEPH, Australian National University, Canberra, Australia, 4Escarpment Cancer Research Institute, Hamilton, ON, Canada, 5Department of Radiation Oncology, Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, ON, Canada, 6Monash University Faculty of Medicine, Clayton, Australia, 7University of Sydney, Sydney, Australia, 8Division of Radiation Oncology, Juravinski Cancer Centre, McMaster University, Hamilton, ON, Canada, 9The Ottawa Hospital, Ottawa, ON, Canada, 10Alfred Health, Melbourne, Australia, 11Cancer Council Victoria, Melbourne, Australia, 12BC Cancer, Vancouver, BC, Canada, 13Crown Princess Mary Cancer Centre, Westmead, Australia, 14Peter MacCallum Cancer Centre, Melbourne, Australia, 15Westmead Hospital, Westmead, Australia

Purpose/Objective(s): The TOAD (TROG 03.06; NCT00110162) phase 3 randomized trial showed that immediate androgen deprivation therapy (IADT) improved overall survival (OS) and time to clinical progression compared with delayed ADT (DADT) in progressive or relapsed prostate cancer patients after radical radiation therapy (RT) or prostatectomy + RT. ELAAT (NCT00439751) was a similarly designed trial but failed to reach its accrual goal. The two investigative teams planned a combined analysis before ELAAT was activated. This combined analysis seeks to determine if IADT improves a number of clinical outcomes including overall survival.

Materials/Methods: The PSA failures from TOAD and 78/79 patients accrued to ELAAT were combined (1 patient was excluded due to castrate resistant prostate cancer (CRPC)). Participants for both trials were randomized 1:1 to IADT or DADT. The primary endpoint was all-cause mortality by intention-to-treat. Secondary endpoints were cancer-specific mortality (CSM), local progression, distant progression, CRPC, and prostate cancer complications (PCC).

Results: 261 patients from TOAD and 78 patients from ELAAT were followed a median of 5.0y. TOAD patients were younger (mean age 70.5 vs 73.8y) and more had a relapse-free interval <2y from RT (30% vs 10%). In the DADT arms, 63% received ADT a median of 1.58y for TOAD; 38% received ADT a median 1.65y for ELAAT. For patients receiving ADT, the mean pre-ADT PSAs were 3.52 and 30.2 ng/ml in the IADT and DADT arms of TOAD and 3.98 and 18.1 ng/ml in ELAAT. There were 60 deaths, 40 and 20 respectively. Overall, for IADT and DADT arms the proportions of deaths in each trial were 15%, 11%, 19% and 26%, 27% and 24%. All-cause mortality (HR 0.75, 95% CI 0.40, 1.41; p = 0.37) and CSM (HR 0.57, 95% CI 0.22, 1.49) were not statistically different between IADT and DADT. Time to local progression (survival time ratio 1.97, 95% CI 1.28, 3.04; p=0.002) and distant progression (survival time ratio 1.28, 95% CI 1.04, 1.58; p=0.02) was higher while PCC (3.7 v 7.5%, p=0.06) was lower with IADT. CRPC outcomes will be presented at conference.

Conclusion: No difference in OS was detected between IADT and DADT in the combined analysis. A possible explanation is that ELAAT accrued older patients with lower risk of CSM and had a smaller difference in PSA between the IADT and DADT arms. Not all relapsed men need IADT; many will die without ever needing ADT and never have a complication or develop CRPC. Further work is needed to identify patients who will benefit from IADT and those suitable for DADT.

Author Disclosure: D. Loblaw: Consultant; Glaxo Smith Kline, Merck, Bristol-Myers Squibb, Novartis, Roche, Astellas, Janssen Oncology, AbbVie, Bayer, Ferring. Travel Expenses; Janssen Oncology, Astellas. Patent/License Fees/Copyright; Sunnybrook Research Institute. J. Bassett: None. C. D'Este: None. G. Pond: Employee; Roche. P. Cheung: Independent Contractor; Ontario Ministry of Health and Long-Term Care. Research Grant; Sanofi Aventis, Pfizer, Abbvie. M. Frydenberg: None. M.T. King: Research Grant; AbbVie, Bristol-Myers Squibb. H. Lukka: None. J.L. Millar: Stock; Resmed, Estia Health. T. Pickles: Honoraria; AbbVie, Ferring, Bayer, Sanofi. Consultant; AbbVie. K. Tai: None. H. Woo: Consultant; Janssen Oncology. Speaker's Bureau; Astellas, Ipsen.

D. Andrew Loblaw, MD, MSc, FRCPC

Odette Cancer Centre

Dr. Loblaw Medicine Professional Corp: President: Employee

AbbVie: Consultant, Honoraria; Astellas: Advisory Board, Consultant, Honoraria, Travel Expenses; Bayer: Consultant, Honoraria; Bristol-Myers Squibb: Consultant; Ferring: Consultant; Glaxo Smith Kline: Consultant; Janssen: Advisory Board, Honoraria; Janssen Oncology: Consultant, Travel Expenses; Merck: Consultant; Novartis: Consultant; Roche: Consultant; TerSera: Honoraria

Sunnybrook Research Institute: Patent/License Fees/Copyright

Prostate Cure Foundation: Founder and Chair

Dr Andrew Loblaw is a Radiation Oncologist, Clinician Scientist, and dual Professor in the Department of Radiation Oncology and the Institute of Health Policy Management & Evaluation at the University of Toronto.

He received a Bachelor of Science in Physics from the University of British Columbia and his Doctor of Medicine from Queen’s University. He completed his specialty training in Radiation Oncology concurrent with a Masters degree in Clinical Epidemiology to graduate from Royal College’s Clinician Investigator Program all at the University of Toronto.

Dr Loblaw’s clinical practice and research interest focus on improving outcomes for men with prostate cancer and the healthcare system. He has a particularly interest in the design and conduct of clinical trials, the generation and dissemination of evidence-based guidelines and in image-guided radiotherapy.

Dr Loblaw is an Ontario Association of Radiation Oncology Clinician Scientist and a Scientist at the Sunnybrook Research Institute. A Fellow of the American Society of Clinical Oncology (FASCO), he was previous Co-Chair of the ASCO’s Genitourinary Advisory Group and remains Co-Chair of the GU group for Cancer Care Ontario’s Program in Evidence-Based Care.


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303 - Timing of Androgen Deprivation Therapy for Prostate Cancer Patients After Radiation: Planned Combined Analysis of Two Randomized Phase 3 Trials


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