EORTC_AMAROS_trial临床试验课件

1、EORTC_AMAROS_trial临床试验课件 Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer patients: final analysis of the EORTC AMAROS trialBy the EORTC Breast Cancer Group andRadiation Oncology Group In collaboration with the Dutch BOOG Group Name of presenterand ALMANAC Triali

2、sts Group Function of presenterEmiel J.T. Rutgers The Netherlands Cancer Institute, AmsterdamClinical trial information: NCT00014612BackgroundSentinel node SN biopsy has replaced the axillary lymph node dissection ALND if cN0If axillary SN+ AxSN+ and indication for axillary treatment, ALND is standa

3、rd of careALND is associated with high rates of side effectsAxillary radiotherapy AxRT provides good regional control with limited side effects in cN0Deutsch et al, IJROBP 2021 Hoebers et al, Cancer 2000Fisher et al, NEJM 2002Louis-Sylvestre et al, JCO 2004HypothesisAxillary radiotherapy provides lo

4、cal control and survival comparable to ALND with fewer side effects in women with a positive axillary SNEligibility CriteriaInclusionExclusionInvasive breast cancer Multicentric disease0.5-5 cmNeoadjuvant Clinically N0systemic treatmentBCT or mastectomy Previous axillary Any age treatmentInformed co

5、nsentPrior malignancyTrial designAxSN+AxSN+ALNDALNDcT1-2cT1-2SNBRRN0N0AxRTAxRTAxSN-AxSN-Stratification: institutionAdjuvant systemic therapy by choiceObjectivesPrimary: To demonstrate non-inferiority in axillary recurrence rateSecondary: 1. To compare overall survival OS and disease-free survival DF

6、S 2. To compare lymphedema, shoulder function and Quality of Life QoLEndpoints and statistical designPrimary: 5-years axillary recurrence free rateNon inferiority hypothesis design: assumption: ALND 98%; AxRT 96%one-sided log-rank; alpha 0.05; power 80%52 events neededSecondary: Efficacy: OS and DFS

7、Safety: shoulder function, lymphedema, QoLAxRTTiming:Start 12 weeks after SNBExtent:level I + II + III + medial SCDose & schedule:25 x 2 Gy or equivalentQuality control: dummy run Hurkmans et al, Radiother Oncol 2003ALNDTiming:12 weeks after SNBExtent:Level I + II mandatoryLevel III optionalAddi

8、tional AxRT: 4 positive nodesRESULTSAccrual of study 10981Theoretical4,500Study4,000Expected today: 4766Observed today: 48133,500Expected 1y: 2983,000Observed 1y: 205Expected 2y: 8942,500Observed 2y: 5602,000Expected Q4+Q5: 262Observed Q4+Q5: 1591,500Expected Q8+Q9: 298Observed Q8+Q9: 2051,000500023

9、/09/02 22/09/04 22/09/06 21/09/08 21/09/10 20/09/12Timeyears from start2001- 2021: 4806 patients enrolled 4766 requiredNumber of patientsAll included patientsn 4806SNB not identified SNB other SNB negative AxSNB positiveN 132 2.7% N 120 2.5%N 3131 65.1% N 1425 29.7%Intent-to-treat ITT ALND AxRT samp

10、leN 744 N 68110not eligible 8ExcludedExcluded85 ITC only before amendment 67N 146N 14651 Non-compliance 71ALND Per Protocol PP AxRT N 598 sampleN 535Efficacy analyses OS and DFS: 1. per protocol PP2. by intent-to-treat ITT Both PP and ITT analyses gave similar results Intent-to-treat analysis report

11、edTreatment complianceALND AxRT744 pts 681 ptsRandomized treatment631 84.8 %590 86.6 %Both treatments415.5 %1 0.1 %Cross-over466.2 %68 10.0 %No axillary treatment243.2 %223.2 %Baseline clinical ALND AxRT744 pts 681 ptsMedian age Q1-Q356 48 - 64 55 48 - 63Menopausal stage38.1 % 42.5 %pre-menopausalpo

12、st-menopausal57.7 % 54.5 %Median tumor size Q1-Q317 mm 13 - 22 18 mm 13 - 23Grade24.1 % 22.6 %147.8 % 45.7 %225.8 % 29.4 %359.2 %Pre-operative ultrasound axilla 61.5 %Baseline treatment ALND AxRT744 pts 681 ptsBreast surgery 81.9 %BCS 81.8 %17.1 %Mastectomy 17.8 %Systemic treatment61.3 %chemotherapy

13、 60.9 %hormonal therapy 77.1 %78.6 %immunotherapy 6.4 %6.0 %no systemic treatment 9.4 %9.0 %RT breast/chest wall 84.8 % 87.7 %SN results ALND AxRT744 pts 681 ptsMedian number of SN 2 1-3 2 1-3removed Q1-Q3Size of metastases in SN macrometastases 59.4 % 61.5 %micrometastases 28.9 % 28.6 %ITC 11.7 % 9

14、.8 %Straver et al, Ann Surg Oncol 2021ALND results ALND 744 ptsMedian number of all nodes removed Q1-Q3 15 12-20Number of additional positive nodes besides SN0 67.1 %25.0 %1-37.8 % 4Axillary recurrence rate5-years axillary recurrence rate: ALND 0.43% 4 / 744 events 0.54% AxRT 1.19% 7 / 681 events 1.

15、03% hypothesis 2%Consequence: planned comparison is underpoweredAxillary recurrence rate SN-5-years axillary recurrence rate: 0.72% 25/3131 events 0.80%Disease-free survival P 0.18Overall survival Breast cancer specific deaths:ALND: 53 7.1 %AxRT: 54 7.9 %P 0.34Results side effects50-70% form complia

16、nce at all time pointsLymphedema of the armMeasured: 1, 3 and 5 years after treatmentItems:Clinical observationTreatment for edema:- sleeve garment- lymph drainage therapy- compression therapyLymphedema: clinical observation and/or treatment40.0%29.8%21.7%16.7%13.6%Years after randomization24Lymphed

17、ema: clinical observation27.8%23.2%22.5%15.1%13.8%10.8%Years after randomizationLymphedema: treatment31.5%20.9%16.8%16.1%9.7%6.6%Years after randomizationShoulder functionMeasured: 1, 3 and 5 years after treatment180°Items:90°1. Ante/retroversion20°-40°2. Ab/adductionShoulder fun

18、ctionResults: No significant differences in all 4 excursionsTrend towards impaired movement after AxRT in first year onlyRelative movement:Excursion treated armExcursion untreated armMultivariate Years after randomizationQuality of LifeMeasured: 1, 2, 3 and 5 years after treatmentQuestionnaire:1. EO

19、RTC-QLQ-C30 core questionnaire version 32. QLQ-BR23 breast cancer moduleResults: No significant differences Selected scales:arm symptoms, pain & body imageQuality of LifeResults: Trend towards more difficulties to move the arm after ARTALNDAxRTTrend towards more swelling after ALNDALND AxRTDiscu

20、ssionThe axillary recurrence rate was far below hypothesized, hence, the trial was underpoweredAxRT: level I + II + III + SCImbalance in AxSN+ patients per arm- independent committee: no explanation Indication for axillary treatment?ConclusionBoth ALND and AxRT provide excellent and comparable locor

21、egional control in AxSN+ patients Significantly less lymphedema after AxRT AxRT can be considered standardAcknowledgementWe are very grateful to all the patients who participated in this trialAcknowledgementResearch fellows: Mila Donker, Marieke Straver, Philip MeijnenPrincipal investigators: Cornel

22、is van de Velde, Robert Mansel, Geertjan van TienhovenEORTC headquarters: Nicole Duez, Leen Slaets, Jan Bogaerts, Carlo Messina, Corneel Coens, the IDMCEORTC Breast Cancer GroupEORTC Radiation Oncology GroupDutch BOOG GroupALMANAC Trialists GroupParticipating institutesArnhem, ZH Rijnstate, the Neth

23、erlands Den Haag, Bronovo ZH, the Netherlands Hardewijk, St Jansdal ZH, the Netherlands Groningen, UMCG, the Netherlands Hardenberg, R?pcke-Zweers ZH, the Netherlands Amsterdam, NKI-AVL, the Netherlands Den Haag, Haga ZH, the Netherlands Firenze, Univ Hosp Careggi, ItalyCardiff, Univ Hosp Wales, Uni

24、ted KingdomDrachten, ZH Nij Smellinghe, the Netherlands Manchester, Manchester Univ Hosp, United Utrecht, Diakonessenhuis, the Netherlands KingdomLeiden, LUMC, the Netherlands Amsterdam, AMC, the Netherlands Torino, San Giovanni Battista Hosp, Italy Den Haag, MCH Westeinde, the Netherlands Apeldoorn, Gelre ZH, the Netherlands Ljubljana, Univ Hosp, Slovenia Eindhoven, Catharina ZH, the Netherlands Lille, Centre Oscar Lambret, Fr