CUA 2017: Four vs. 10 Months of Induction Androgen-Deprivation Therapy for Intermittent Therapy (the FIT trial): A Prospective Canadian Urology Research Consortium Randomized Trial

Toronto, Ontario ( Men with metastatic prostate cancer (PCa) are placed on androgen-deprivation therapy (ADT) for control of their disease. However, long-term ADT can have consequences on men’s health, including risk of osteoporosis and heart disease, along with the adverse events associated with it.

As quality of life can suffer while on ADT, the concept of intermittent ADT (IADT) was introduced as an alternative1 – periods of ADT cessation to allow for normal testosterone recovery. Proven to be non-inferior to continuous ADT, IADT is now well-established in patients with non-metastatic disease. There have been only 4 Phase III trials of IADT vs. continuous ADT with more than 500 patients (PR7, SWOG 9346, ICELAND, and SEUG) – IADT was non-inferior in both studies of PSA failure (PR7 and ICELAND) and inconclusive in the one study of metastatic patients (SWOG 9346). 

However, the optimal induction course of ADT has never been determined. How long of an induction course is needed before allowing for the first break from therapy? In this prospective, open-label, multicentre, randomized Canadian trial, 101 patients were enrolled, and 91 were randomized between 4 and 10 months of degarelix. Only patients with biochemical recurrence after definitive local therapy with surgery or radiation, a rising prostate-specific antigen (PSA) >5.0, serum testosterone > 8 nM/dL, and no bone metastases were included in the study. Patients were stratified for PSA < or >10 and Gleason score  ≤ or >7. The primary endpoint was the time until PSA reached 5.0 during the off-treatment interval.

Patients were treated with degarelix as the study was funded by Ferring. Patients were given induction dose of 240 mg, and then either 3 or 9 months of 80 mg monthly dose. 

Of the men included, the median age was 75 and median PSA was 12; there was no significant difference between the two groups in median age, PSA, body mass index (BMI), racial distribution, Gleason score, T stage, Eastern Cooperative Oncology Group (ECOG), smoking history, or baseline testosterone. 

The median time off treatment was 22.8 months. There was no difference between the two groups in the median off-treatment interval (p=0.38). PSA nadir <0.1, but not baseline PSA ≤ or >10, predicted for more prolonged time off treatment.  There was no difference in time to testosterone recovery between the groups (median 7.2 months).

This important study indicates that a short induction course of just 4 months can be sufficient for initiation of IADT. By reducing the start interval, patients can get back to improved QOL sooner. Ultimately, these patients need to be followed to identification of disease progression to ensure there is no difference in time to progression. 

Dr. Klotz felt that this is now his standard of practice – he routinely used 4 month induction courses, as long as the PSA has nadired < 0.1.

Presented By: Laurence H. Klotz, MD, Urology, Sunnybrook Health Science Centre, University of Toronto, Toronto, ON

Co-Authors: Andrew Loblaw1, D. Robert Siemens2, Paul Jr. Ouellette3, Anil Kapoor4, Fred Saad5
Institutions: Radiation Oncology, Sunnybrook HSC, Toronto, ON, Canada1; Urology, Queen's University, Kingston, ON, Canada2; Urology, Granby Hospital, Granby, QC, Canada3; Urology, McMaster University, Hamilton, ON, Canada4; Urology, Université de Montréal, Montreal, QC, Canada5

Written By: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto   Twitter: @tchandra_uromd at the  72nd Canadian Urological Association Annual Meeting - June 24 - 27, 2017 - Toronto, Ontario, Canada

1. Klotz LH, Herr HW, Morse MJ, Whitmore WF Jr. Intermittent endocrine therapy for advanced prostate cancer. Cancer. 1986 Dec 1;58(11):2546-50. Erratum in: Cancer 1987 May 15;59(10):43.