Кой има полза от адювантна ендокринна терапия при карцином на гърда с какво и колко дълго? д-р Красимир Койнов МБАЛ Сердика, София
Декларация Консултации и хонорари: Roche, Boerhinger Ingelheim, Astra Zeneca, Novar>s, Eli Lilly, Astelas, Sanofi Aven>s, Intellect Pharma, Merck, Pfizer, Amgen, Servier, MSD
Extended Tamoxifen Trials in Breast Cancer: ATLAS and attom Yr 5 Yr 10 ATLAS Pts with EBC Tamoxifen treatment for treated with adjuvant 5 additional yrs (n = 6454) tamoxifen for > 4 yrs; any ER, age, nodal status; international trial No additional Tamoxifen (n = 6640) Pts with EBC treated with adjuvant tamoxifen for ~ 5 yrs; ER+ or untested; any age, nodal status; UK trial attom Tamoxifen treatment for 5 additional yrs (n = 3485) No additional Tamoxifen (n = 3468)
ATLAS Trial: Efficacy of ConTnuing vs Stopping Adj Tamoxifen in ER+ BC 50 Recurrence ConGnue tamoxifen to 10 yrs Stop tamoxifen at 5 yrs 50 Breast Cancer Mortality CumulaCve incidence (%) 40 30 20 10 5-9 yrs RR: 0.90 (0.79-1.02) 10 yrs RR: 0.75 (0.62-0.90) All yrs: log-rank P =.002 PRR: 15% (SE: 5%) 14.5% 13.1% 25.1% 21.4% 40 30 20 10 5-9 yrs RR: 0.97 (0.79-1.18) 10 yrs RR: 0.71 (0.58-0.88) All yrs: log-rank P =.01 PRR: 20% (SE: 5%) 6.0% 15.0% 12.2% 0 0 Diagnosis 5 ATLAS Entry 10 EOT Davies C, et al. Lancet. 2013;381:805-816. 15 10 Yrs Since Entry 0 0 Diagnosis 5 ATLAS Entry 5.8% 10 EOT 15 10 Yrs Since Entry
attom and ATLAS: OS in ER+ Breast Cancer With 5 vs 10 Yrs of Tam Rate RaCo by Period (95% CI) 10 vs 5 Yrs of Tam attom + ATLAS (n = 17,477 ER+) Yrs 5-9 0.99 (0.89-1.10) Yrs 10+ 0.84 (0.77-0.93) P =.0007 All yrs 0.91 (0.84-0.97) P =.008 Gray RG, et al. ASCO 2013. Abstract 5.
attom and ATLAS: Endometrial Cancers With 5 vs 10 Yrs of Tamoxifen Absolute hazard: 0.5% Event 10-Yr Tam, n (%) 5-Yr Tam, n (%) Rate RaCo (95% CI) Endometrial cancer 102 (2.9) 45 (1.3) 2.20 (1.31-2.34) Endometrial cancer death 37 (1.1) 20 (0.6) 1.83 (1.09-3.09) P Value <.0001.02 Gray RG, et al. ASCO 2013. Abstract 5.
Phase III TEXT and SOFT: Adjuvant OFS + Tam or Exe vs Tam Alone in HR+ EBC Stratified by trial, use of chemotherapy, nodal status TEXT 5 yrs Premenopausal pts with HR+ BC 12 wks after surgery (N = 2672; FU: 5.6 yrs) Tamoxifen 20 mg/day + OFS* (n = 1328) Exemestane 25 mg/day + OFS* (n = 1332) Joint Analysis Tamoxifen + OFS* (n = 2344) SOFT Premenopausal pts with HR+ BC 12 wks after surgery (if no chemo) or 8 mos after chemo (N = 3066; FU: 5.6yrs ) Exemestane 25 mg/day + OFS* (n = 1014) Tamoxifen 20 mg/day + OFS* (n = 1015) Tamoxifen 20 mg/day (n = 1018) Exemestane + OFS* (n = 2346) *OFS TEXT: triptorelin 3.75 mg IM every 28 days for 6 mos, then opgonal bilateral oophorectomy or irradiagon SOFT: choice of method Pagani O, et al. ASCO 2014. Abstract LBA1.
SOFT Trial Primary Analysis: DFS With OFS + Tamoxifen vs Tamoxifen Alone 100 PaCents Alive and Disease Free, % 80 60 40 20 0 Tamoxifen Tamoxifen + OFS 5.6 yrs median follow-up Tamoxifen Tamoxifen + OFS 5 Yr, % 84.7 86.6 HR 0.83 0 1 2 3 4 5 6 Yrs Since RandomizaCon 95% CI 0.66-1.04 P Value.10 17% relagve improvement (P =.10; NS) 22% relagve improvement with mulgvariate adjustment (P =.03) Francis P, et al. SABCS 2014. Abstract S3-08. Francis PA, et al. N Engl J Med. 2015;372:436-446
SOFT Trial Secondary Endpoint: DFS With OFS + Tam or Exemestane vs Tam Alone 100 DFS, % 80 60 40 20 0 T T + OFS E + OFS T T + OFS E + OFS Pts, n 1018 1015 1014 Events, n 160 139 113 5-Yr % 84.7 86.6 89.0 HR 0.83 0.68 0 1 2 3 4 5 95% CI 0.66-1.04 0.53-0.86 6 RelaGve reducgon in BC recurrence T + OFS vs T: 17% (P =.09) E + OFS vs T: 32% (P <.05) Yrs Since Randomization Francis P, et al. SABCS 2014. Abstract S3-08. Francis PA, et al. N Engl J Med. 2015;372:436-446.
SOFT Trial: Exploratory Analysis for Only Pts Who Received Adjuvant Chemo 5-Yr Outcome, % OFS + Tamoxifen Tamoxifen Alone Risk Reduction P Value (Assessment of Treatment-Effect Heterogeneity by Chemo Cohort) DFS 80.7 77.1 18.96 (NS) DDFS 84.8 83.6 13.62 (NS) FBC 82.5 78.0 22.54 (NS) OS 94.5 90.9 36.03 Francis PA, et al. N Engl J Med. 2015;372:436-446.
SOFT Trial: Efficacy Outcomes for OFS + Exemestane vs Tamoxifen Alone 5-Yr Outcome, % OFS + Exemestane Tamoxifen Alone Risk Reduction P Value DFS 89.0 84.7 32 <.05 DDFS 93.0 90.7 29 <.05 FBC 95.3 86.4 36 <.05 OS 95.3 95.1 3 NS Francis PA, et al. N Engl J Med. 2015;372:436-446.
SOFT Trial: Conclusions for OFS + Tam or Exemestane vs Tam in HR+ EBC Adding OFS to tamoxifen did not provide significant benefit in overall study populagon For women who were at sufficient risk for recurrence to warrant adjuvant chemotherapy and who remained premenopausal, the addigon of OFS improved disease outcomes ParGcular improvement was seen with the use of exemestane plus OFS Francis PA, et al. N Engl J Med. 2015;372:436-446.
TEXT and SOFT: Conclusions Exemestane + OFS significantly improved DFS, BCFI, and DRFI vs tamoxifen + OFS, but no clear OS benefit (too early??) Safety profile of exemestane + OFS similar to that seen with AIs in postmenopausal women Exploratory subset analysis suggested pargcular benefit in pts who were at higher risk and received chemotherapy Pagani O, et al. ASCO 2014. Abstract LBA1.