Important Studies Flashcards
Treatment of primary
STOPCAP M1: Burdett et al, Eur Urol, 2019. Metastatic prostate cancer. “Meta-analysis of M1 patients in STAMPEDE and HORRAD. RT to prostate + ADT vs. ADT “. “If <5 bone mets, RT to prostate improved OS.
RT improved BF and FFS in all M+. For <5 bone mets, 3-yr OS 77% vs. 70%. In all M+, RT improved 3-yr BF, 25% vs. 36%”. RT to the primary prostate tumor in the setting of ≤5 bone mets improves OS in this meta-analysis.
Treatment of primary, chemo, ADT
STAMPEDE: “Parker et al, ASTRO, 2014. “Must have 2/3: stage T3/T4, PSA >40, GS 8-10, with intention to treat with RT OR newly diagnosed node postitive disease or mets. High met burden: visceral mets and/or ≥4 bone mets with ≥1 outside the vertebra or pelvis. Low met burden: anything less than high burden”. “A adaptive trial that opens new arms and closes accrued arms with time
ADT in all plus one of the following: RT (RT required in non metastatic patients), zoledronic acid, docetaxol, ZA plus docetaxol, celecoxib, abiraterone, metformin. RT choice of 55 Gy/20 fx or 36 Gy/6 fx once weekly”“•RT to prostate in those with low met burden: 3-yr OS 81% vs. 73%. Node+: FFS improved with RT: 71% vs. 47%. Docetaxel: Median OS improved 81 mos taxol vs. 71 (standard of care) vs. 76 (ZA + docetaxol). Benefit in all metastatic subgroups, low or high. Abiraterone: HR for OS and FFS improved for metastatic and locally advanced patients”
“There is OS and FFS benefit with RT to prostate in those with low metastatic burden, defined as 1-3 bone mets or any # of pelvic or vertebral body mets.
RT in node positive patients improves FFS.
Docetaxol in locally advanced, N+, and M+ improves OS. There is benefit in low and high burden metastatic disease.
Abiraterone improves OS and FFS for metastatic and locally advanced prostate cancer.”
Oligometastatic
SABR-COMET: “Palma et al, Lancet, 2019. “≤5 oligometastases (93% were 1-3) any histology, controlled primary tumor from definitive treatment (such as chemoRT) (most were lung, breast, colorectal, prostate. Misc was about 1/3)”. “Phase II: SBRT and palliative standard of care vs. palliative standard of care. (SBRT to 30-60 Gy/ 3-8 fx or single fx of 16-24 Gy for brain, spine). Median OS 50 vs. 28 mos. 5-yr OS 42% vs. 18%, p=0.006
grade 5 toxicity 4.5% (n=3) vs. none
ORIOLE: Phillips et al, JAMA Oncol, 2020. “recurrent ADT-sensitive prostate cancer, ≤3 oligometastatic lesions s/p treatment to primary (RT or RP) no ADT in last 6 months”“→SBRT to metastatic lesions vs. observation”.
6-mo progression 19% vs. 61%
6-mo PSMA avid new lesions 19% vs. 63%
Median PFS not reached vs. 5.8 mo
SBRT led to T cell clonal expansion, p=0.03
(OS is not an endpoint)
continuous vs. intermittent ADT
SWOG: Hussain et al, NEJM, 2013. newly diagnosed metastatic disease, PSA ≥5, All get 7 mos ADT initially, then if PSA falls to ≤4, randomized to intermittent vs continuous ADT. Noninferiority study. No difference in OS. Median OS 5.8 years in continuous vs. 5.1 years in intermittent (HR for intermittent 1.10, p=0.25). No difference with minimal vs. extensive disease.
Radium 223
ALSYMPCA: Parker et al, NEJM, 2013. Castration resistant prostate cancer with bone metastases. “→6 injections of radium-223 vs. placebo and best standard of care (2:1 randomization). Eligibility: ANC ≥ 1500, Plt ≥ 100, Hgb ≥ 10 at first dose. Subsequent doses: ANC ≥ 1000 and Plt ≥ 50”. “Median OS improved with radium 14.9 mos vs. 11.3 mos. The study was terminated early for efficacy at interim analysis. Number of adverse effects in radium-223 group was significantly lower than in placebo arm
Radium-223 patients had improved QOL in FACT-P score”
ADT, castrate resistant: Darolutamide
ARAMIS: Fizazi et al, NEJM, 2019. nonmetastatic castrate resistant, PSA DT ≤10 mos. “→darolutamide indefinitely + ADT vs. ADT alone”. “median DMFS 40 mos vs. 18 mos
Also improved OS. Grade ≥3 toxicity and discontinuations similar”
ADT, castrate resistant: Apalutamide
SPARTAN: Smith et al, NEJM, 2018. nonmetastatic castrate resistant, PSA DT ≤10 mos. “→apalutamide indefinitely + ADT vs. ADT alone”. “median DMFS 41 mos vs. 16 mos. More toxicity and discontinuation with apalutamide”
ADT, castrate resistant: Enzalutamide
PROSPER: Hussain et al, NEJM, 2018. nonmetastatic castrate resistant, PSA DT ≤10 mos. “→enzalutamide indefinitely + ADT vs. ADT alone”“median DMFS 37 mos vs. 15 mos. median BF 37 mos vs. 4 mos. OS 11% vs. 13%
Grade ≥3 toxicity 31% vs. 23%”
