Negoti-18.
Top Line: Last year’s ASCO GU brought us a teaser in abstract form indicating that 18 months of androgen deprivation therapy (ADT) is just as good as 36 months, at least in terms of survival for men with high risk (HR) prostate cancer. Only 13 months later, we have the full manuscript and good thing we do.
The Study: Canadians hate lollygagging when it comes to any cancer regimen, so they designed this phase 3 trial to see if the standard 36 months of ADT (i.e., the “standard” when this trial opened in 2000) is really earning its 3 year keep. All 630 enrollees had clinically HR disease and received standard (again, in 2000) 3D-conformal radiation of 44 / 70 Gy to whole pelvis / prostate at 2 Gy per fraction over 7 weeks with Zoladex (aka goserelin, aka a GnRH agonist) injections starting 4 months prior to radiation plus oral Casodex (aka bicalutamide, aka an androgen receptor blocker) daily for the first month. The randomization finally came with the duration of Zoladex after radiation, either for another 30 versus 12 months. Interestingly, this was not designed as a noninferiority study but rather to directly compare two primary endpoints: overall survival (OS) at 5 years and quality of life (QoL) throughout 5 years. While OS was exactly the same at 10 years (62%), as reported in the abstract, the curves came pretty darn close to significantly separating at 5 years (91% with 36m versus 86% with 18m). In other words, 18m wouldn’t have met any noninferiority threshold we’ve ever seen. Not to mention the biochemical failure rates were significantly higher at 10 years (25% versus 31% with 18m). But, hey, QoL was “significantly” better across 6 of 21 scales in the 18m arm—though, as the authors note, none of these reached “clinical relevance.”
Bottom Line: Like in breast cancer, hormone blockade for HR prostate cancer likely confers a steady relative (and continually diminishing absolute) disease-free survival advantage...forever. So length of ADT is ultimately left up to negotiations between you, your patient, and his side effects. | Nabid, Eur Urol 2018
The Study: Canadians hate lollygagging when it comes to any cancer regimen, so they designed this phase 3 trial to see if the standard 36 months of ADT (i.e., the “standard” when this trial opened in 2000) is really earning its 3 year keep. All 630 enrollees had clinically HR disease and received standard (again, in 2000) 3D-conformal radiation of 44 / 70 Gy to whole pelvis / prostate at 2 Gy per fraction over 7 weeks with Zoladex (aka goserelin, aka a GnRH agonist) injections starting 4 months prior to radiation plus oral Casodex (aka bicalutamide, aka an androgen receptor blocker) daily for the first month. The randomization finally came with the duration of Zoladex after radiation, either for another 30 versus 12 months. Interestingly, this was not designed as a noninferiority study but rather to directly compare two primary endpoints: overall survival (OS) at 5 years and quality of life (QoL) throughout 5 years. While OS was exactly the same at 10 years (62%), as reported in the abstract, the curves came pretty darn close to significantly separating at 5 years (91% with 36m versus 86% with 18m). In other words, 18m wouldn’t have met any noninferiority threshold we’ve ever seen. Not to mention the biochemical failure rates were significantly higher at 10 years (25% versus 31% with 18m). But, hey, QoL was “significantly” better across 6 of 21 scales in the 18m arm—though, as the authors note, none of these reached “clinical relevance.”
Bottom Line: Like in breast cancer, hormone blockade for HR prostate cancer likely confers a steady relative (and continually diminishing absolute) disease-free survival advantage...forever. So length of ADT is ultimately left up to negotiations between you, your patient, and his side effects. | Nabid, Eur Urol 2018
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