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Ral5.3
Raloxifen (Evista) – Forschung
Überwiegend Mechanismus / Beobachtung
8 begutachtete Studien
Was die Evidenz sagt
Überwiegend Mechanismus / Beobachtung
Die meisten Studien zu Raloxifen (Evista) sind mechanistisch oder beobachtend statt RCTs, die einen klinischen Effekt messen — betrachte die Ergebnisse als vorläufig.
Die meiste Evidenz stammt aus mittelwertigen Meta-Analysen und randomisierten Studien, veröffentlicht 1999–2013 mit einer typischen Studiengröße von 7,705 Teilnehmenden.
Basierend auf 8 Studien · 1 Meta-Analyse · 5 RCTs · 50,509 Teilnehmende insgesamt
Konfidenz
Hohe Konfidenz
Nach Outcome
Breast cancer & postmenopausal
Überwiegend Mechanismus / Beobachtung7 Studien
Bone health & osteoporosisIn MORE wurde das Risiko neuer vertebraler Frakturen gesenkt und die Knochenmineraldichte bei postmenopausalen Frauen mit Osteoporose erhöht · Monate bis Jahre
Überwiegend Mechanismus / Beobachtung3 Studien
Cardiovascular & thrombosis
Zu wenige bewertete Studien2 Studien
Safety profile
Zu wenige bewertete Studien2 Studien
Ältere Forschungsbasis
Neueste Studie von 2013 · Neueste Meta-Analyse: 2013
199920062013
1RCTn=7,705 · very large study1999
Risk of vertebral fracture was reduced in both study groups receiving raloxifene (for 60-mg/d group: relative risk [RR], 0.7; 95% CI, 0.5-0.8; for 120-mg/d group: RR, 0.5; 95% CI, 0.4-0.7).
Ettinger B, Black DM, Mitlak BH, Knickerbocker RK, Nickelsen T, Genant HK, et al. · JAMA (1999)
MORE: multicenter, randomized, double-blind, placebo-controlled trial of raloxifene 60 or 120 mg/day in 7,705 postmenopausal women with osteoporosis, followed up to 36 months
New vertebral fractures occurred in 10.1% on placebo vs 6.6% (60 mg) and 5.4% (120 mg) raloxifene — a 30-50% relative reduction — with increased bone mineral density
Honest limit baked into the same trial: raloxifene did NOT significantly reduce non-vertebral fractures, and it increased venous thromboembolism risk
Thirteen cases of breast cancer were confirmed among the 5129 women assigned to raloxifene vs 27 among the 2576 women assigned to placebo (relative risk [RR], 0.24; 95% CI, 0.13-0.44; P<.001).
Cummings SR, Eckert S, Krueger KA, Grady D, Powles TJ, Cauley JA, et al. · JAMA (1999)
Pre-specified breast-cancer analysis of the MORE RCT (7,705 postmenopausal women with osteoporosis), followed a median 40 months
Raloxifene cut invasive breast cancer ~76% overall (RR 0.24) — the reduction confined to estrogen-receptor-positive disease, with no effect on ER-negative tumors
The same trial documented increased venous-thromboembolism risk and the absence of an endometrial-cancer signal (unlike tamoxifen)
Raloxifene had no significant effect on the risk of primary coronary events (hazard ratio, 0.95)... but raloxifene was associated with an increased risk of fatal stroke (hazard ratio, 1.49) and venous thromboembolism (hazard ratio, 1.44).
Barrett-Connor E, Mosca L, Collins P, Geiger MJ, Grady D, Kornitzer M, et al. · N Engl J Med (2006)
RUTH: randomized, double-blind, placebo-controlled trial of raloxifene 60 mg/day in 10,101 postmenopausal women with or at high risk of coronary heart disease, median follow-up 5.6 years
NO reduction in coronary events (HR 0.95) — the cardiovascular hypothesis failed — while invasive breast cancer (HR 0.56) and clinical vertebral fractures (HR 0.65) were reduced
MANDATORY counter-evidence: significantly increased FATAL STROKE (HR 1.49) and venous thromboembolism (HR 1.44, including DVT and pulmonary embolism)
There were 163 cases of invasive breast cancer in women assigned to tamoxifen and 168 in those assigned to raloxifene (incidence, 4.30 per 1000 vs 4.41 per 1000; risk ratio [RR], 1.02; 95% CI, 0.82-1.28).
STAR P-2: prospective, double-blind, randomized head-to-head trial of tamoxifen 20 mg/day vs raloxifene 60 mg/day in 19,747 postmenopausal women at increased breast-cancer risk
Raloxifene was statistically equivalent to tamoxifen for preventing INVASIVE breast cancer (RR 1.02), with fewer uterine cancers (RR 0.62) and fewer thromboembolic events than tamoxifen
Honest limit: raloxifene was somewhat LESS effective against noninvasive (in situ) breast cancer (80 vs 57 cases; RR 1.40)
Overall, we noted a 38% reduction (hazard ratio [HR] 0.62, 95% CI 0.56-0.69) in breast cancer incidence... Thromboembolic events were significantly increased with all SERMs (odds ratio 1.73, 95% CI 1.47-2.05).
Cuzick J, Sestak I, Bonanni B, Costantino JP, Cummings S, DeCensi A, et al. · Lancet (2013)
SERMs reduced breast-cancer incidence 38% over 10 years (HR 0.62), the effect larger in the first 5 years and confined to ER-positive disease
Carries the mandatory class counter-evidence: thromboembolic events significantly increased (OR 1.73); vertebral fractures reduced 34% but only a small non-vertebral effect (HR 0.93)
Over the 8 years of both trials, the incidences of invasive breast cancer and ER-positive invasive breast cancer were reduced by 66% (HR = 0.34; 95% CI = 0.22 to 0.50) and 76% (HR = 0.24; 95% CI = 0.15 to 0.40), respectively, in the raloxifene group.
Martino S, Cauley JA, Barrett-Connor E, Powles TJ, Mershon J, Disch D, et al. · J Natl Cancer Inst (2004)
CORE: extension of the randomized MORE trial giving 4 additional years of raloxifene 60 mg/day (n=3,510) vs continued placebo (n=1,703)
Invasive breast cancer fell 59% during CORE and 66% across the combined 8 years; ER-positive disease fell 76%, with no effect on ER-negative cancer
Demonstrates durability of the breast-cancer benefit out to 8 years of continuous treatment
Raloxifene therapy was associated with a reduced risk of invasive breast cancer in postmenopausal women irrespective of the presence/absence of risk factors; its effect was greater in women with a family history of breast cancer.
Lippman ME, Cummings SR, Disch DP, Mershon JL, Dowsett SA, Cauley JA, et al. · Clin Cancer Res (2006)
Pre-specified subgroup analysis of pooled MORE and CORE trial data (N=7,705 and 4,011) of raloxifene vs placebo, stratified by breast-cancer risk factors
Breast-cancer risk reduction held across subgroups (hazard ratios 0.11-0.67, i.e. 33-89% reductions), with a significant treatment-by-family-history interaction (greater benefit with family history)
Shows the benefit is not confined to a narrow risk band — it generalizes across the osteoporotic population, supporting the breast-cancer-risk-reduction indication
Mean reduction in breast nodule diameter was 2.1 cm (95% CI 1.7, 2.7, P <.0001) after treatment with tamoxifen and 2.5 cm (95% CI 1.7, 3.3, P <.0001) with raloxifene... a greater proportion had a significant decrease (>50%) with raloxifene (86%) than tamoxifen (41%).
Lawrence SE, Faught KA, Vethamuthu J, Lawson ML. · J Pediatr (2004)
Retrospective chart review of 38 adolescents with persistent pubertal gynecomastia treated with raloxifene or tamoxifen (a 3-9 month course) versus reassurance
Raloxifene reduced breast-nodule diameter by a mean 2.5 cm (P<.0001), with some improvement in 91% and a major (>50%) response in 86% — a higher major-response rate than tamoxifen
Honest limit: small, retrospective, no controls beyond reassurance; the authors explicitly call for prospective confirmation, and there are no controlled trials in adult male gynecomastia