Maintenance versus discontinuation of androgen deprivation therapy during continuous or intermittent docetaxel administration in castration-resistant prostate cancer patients: A multicentre, randomised Phase III study by the Piemonte Oncology Network

Use of Sequential Multiple Assignment Randomized Trials (SMARTs) in oncology: systematic review of published studies

“…Among trials’ results reports and protocols, nine were published in oncology journals [ 11 , 12 , 14 , 15 , 18 , 19 , 22 – 24 ], three in experimental and research medicine journals [ 25 – 27 ], two in internal and general medicine journals [ 10 , 16 ]. The other five records were published in specialised journals in other areas of medicine, including clinical neurology [ 17 ], respiratory system [ 20 ] and peripheral vascular diseases [ 21 ].…”

“…For study’s objective (3), the minimal detectable standardized effect size was reported according to different remission rates. Bianchi et al [ 14 ] (Trials’ results) Two I stage: maintenance Vs. suspension of androgen deprivation therapy + docetaxel II stage: continuing docetaxel till progression or 10-cycle completion Vs. docetaxel interruption unitl PSA rose by 50% or disease progression PSA response (>50% reduction from baseline) (1) To demonstrate non-inferiority of androgen deprivation therapy suspension (first stage) (2) To compare second-stage treatments Primary endpoint: Overall survival Secondary endpoints: Time to biochemical progression Clinical progression Death from any cause Time to metatsatic progression PSA response Toxicity Quality of life Yes No (sample size based on upfront comparision). Power analysis reported for the second stage according to the expected proportion of subjects undergoing the second stage Fisher et al [ 15 ] (Trials’ results) Two I stage: tamoxifen Vs. placebo II stage: additional 5 years of tamoxifen Vs. placebo Complete initially assigned 5-year tamoxifen treatment No therapy discontinuation No tumour recurrence/secondary primary cancer To compare second-stage treatments Overall survival Disease-free survival No Fu et al [ 26 ] (Protocol) Two I stage: 4 Vs. 8 weeks tobacco longitudinal care II stage: continuing tobacco longitudinal care Vs. tobacco longitudinal care + medication therapy management (incomplete responders) continuing tobacco longitudinal care Vs. less frequet tobacco longitudinal care (complete responders) Response to treatment (complete/incomplete) (1) To compare second-stage treatments among incomplete responders (2) To examine the role of timing of assessment in treatment response (3) To compare second-stage treatments in complete responders (4) To examine the role of smoking in the 7 days prior to respond assessment in incomplete responders (5) Role of lung cancer screening results in smoking abstinence moderation Primary endpoint: Prolonged smoking abstinence Secondary endpoints: Other smoking outcomes Treatment utilisation and satisfaction Lung cancer screening results Perception of cancer risk Yes The study is powered for the second stage.…”

“…Of notice, Tummarello et al [ 24 ] declared that the number of people entering the second randomisation was too small to allow groups’ comparison. Marshall et al [ 21 ] and Bianchi et al [ 14 ] underwent premature closure because of the low recruitment rate.…”

“… If multiple stages are taken into account, method specification: Ancillary analysis Auyeung et al [ 25 ] (Protocol) (1) Mean outcome estimation using marginal mean models (2–3) Standard statistical tests Yes Marginal mean models. No technical details regarding the estimation are reported Bianchi et al [ 14 ] (Trials’ results) Kaplan–Meier method Cox Proportional Hazard model No. Separate analyses were carried out for the first and second stage Subgroup analysis Fisher et al [ 15 ] (Trials’ results) Kaplan–Meier method Log rank test Cox Proportional Hazard Model No.…”

Maintenance of androgen deprivation therapy or testosterone supplementation in the management of castration-resistant prostate cancer: that is the question

“…This issue was addressed in the PON-PC study, a recently published clinical trial where CRPC patients were randomized to receive docetaxel with or without ADT maintenance [ 11 ]. The results showed no difference in efficacy outcomes (OS, radiological and biochemical PFS) between the two arms.…”