ADENDOM UNICANCER UC 0140/1505

Transcription

1 P UCBG 2 14: A prospective multicenter non randomized trial evaluating the effect of EndoPredict (EPclin ) clinicogenomic test on treatment decision making among patients with intermediate clinical risk ADENDOM UNICANCER UC 0140/1505 VERSION 1.0 COORDINATING PIS Pr Frédérique PENAULT LLORCA & Dr Suzette DELALOGE Centre Jean Perrin Centre de Lutte contre le Cancer d'auvergne Clermont-Ferrand - France -

2 Submitted to PLOSone DECISION OF ADJUVANT CHEMOTHERAPY IN INTERMEDIATE RISK LUMINAL BREAST CANCER PATIENTS: A PROSPECTIVE MULTICENTER TRIAL ASSESSING THE CLINICAL AND PSYCHOLOGICAL IMPACT OF ENDOPREDICT (EPCLIN) USE (UCBG 2 14) F Penault Llorca, F Kwiatkowski, A. Arnaud, C Levy, M Leheurteur, L Uwer, O Derbel, A Le Rol, JP Jacquin, C Jouannaud, N Quenel Tueux, V Girre, C Foa, E Guardiola, A Lortholary, S Catala, S Guiu, A Valent, D Boinon, J Lemonnier, S Delaloge & Lefèvre S

3 Adendom study Adendom aimed at determining if EPclin clinico-genomic test had a significant impact on treatment decision making among pts with predefined intermediate /borderline clinical risk Primary objective = impact of EPclin result on chemotherapy receipt (proportion of change between initial decision and physician/patient s shared final choice regarding CT) Secondary objectives = post-test and one year patients reported outcomes

4 Design Primary Objective

5 Patients and Methods Between Dec 2015 and May 2016, 203 patients were enrolled. Women were eligible for the present study if they: - had an histologically confirmed, invasive breast cancer -hadofafully resected localized ER+ Her2- pn0 or pn1mi BC, - were considered by the multidisciplinary team meeting (MTM) of the center as being in a "grey zone" of uncertain adjuvant CT benefit based on classical clinic-pathological assessment, outlined in the following situations: Lobular histology Or grade II Or grade III and pt < 2cm

6 Study worflow EVALUATION OF THE LENGHT OF THE WORKFLOW PATHOLOGY PROCEDURE Workflow for EndoPredict Quantitative RT PCR Results are sent to UNICANCER and the labs Score EPclin Blocks are shipped back Samp prep, ARN extraction EndoPredict preparation kit Shipment

7 Patients characteristics Median Age years /- 10 ( ) Tumor Type Ductal Lobular Other N % 15% 13% Multifocal Yes 24 12% Tumor Grade I II III % 74% 17% ER positive % PR positive % Surgery Lumpectomy Mastectomy % 26% 2 test failures

8 Patients characteristics (2) N Surgery (axilla) Sentinel Node % pt pt1 [pt1c] pt2 pt3 151 [116] % [58] 22% 2.5% pn EPclin Risk Class pn0 pn1mi Low risk High risk % 9.5% 67% 33%

9 Study Results Final administration of chemotherapy according to EPclin Risk class: EPclin Risk Class No change of strategy CT maintained CT absent Change of strategy CT added CT Withdrawn Low Risk 1 (0.7%) 83 (61.5%) 0 (0%) 51 (37.8%) High Risk 37 (56.9%) 7 (10.8%) 15 (23.1%) 6 (9.2%) Total (/200) 38 (19%) 90 (45%) 15 (7.5%) 57 (28.5%) Treatment decision change rate: 72/200 (35.8% 95%CI [ ]). Discordance with the test results in 14/72 (19%) with 6 (8% of decision changes) due to physician/patient s shared final choice. Penault-Llorca et al (SABCS 2016), submitted to PlosOne

10 Results Evolutions of therapeutic strategy according to the RCP and the prognostic EPCLIN classification Overall change rate of decision is 72/200 (35.8% CI-95% = [ ]). In 57 cases, chemotherapy initially planned was discontinued (28.4% [ ]) In 15 cases (7.5% [ ]) it induced an addition of chemotherapy. strictly in line with expectations (30% to 40%)

11 Study Results Final administration of chemotherapy according to EPclin Risk class: EPclin Risk Class No change of strategy CT maintained CT absent Change of strategy CT added CT Withdrawn Low Risk 1 (0.7%) 83 (61.5%) 0 (0%) 51 (37.8%) High Risk 37 (56.9%) 7 (10.8%) 15 (23.1%) 6 (9.2%) Total (/200) 38 (19%) 90 (45%) 15 (7.5%) 57 (28.5%) Treatment decision change rate: 72/200 (35.8% 95%CI [ ]). Discordance with the test results in 14/72 (19%) with 6 (8% of decision changes) due to physician/patient s shared final choice. Penault-Llorca et al (SABCS 2016), submitted to PlosOne

12 Patients reported outcomes - Methods Baseline Follow-up 1 st visit oncologist 2 nd visit oncologist with results H48 post final decision Follow-up visit Evaluation dates D0 D15 D17 1 Year Anxiety (STAI-trait) X Anxiety (STAI-state) X X X X Distress thermometer X X X X Satisfaction (IN-PATSAT-32) X X X X

13 Questionnaire s completion rates Baseline Follow-up 1 st visit oncologist 2 nd visit oncologist with results H48 post final decision Follow-up visit Evaluation dates D0 D15 D17 1 Year Completion rates Mean, out of 201 (%) 178 (88%) 167 (83%) 163 (81%) 171 (85%)

14 Anxiety level Very low Low Moderate High Very high STAI-trait Score, out of [36-45] [46-55] [56-65] > 65 Number of patients (%) (33.5%) 114 (64.8%) 3 (1.7%) Mean STAI-trait at baseline: /- 4.3

15 Anxiety and distress Anxiety and distress increased very significantly at D15 in case of addition of CT, but returned to baseline level at 1-year. EPclin results EPclin results Anova, p <10-7 Anova, p= Anxiety Distress Mean anxiety and distress levels and their evolution over time according to final chemotherapy decision

16 Patients overall satisfaction was initially high but decreased slowly until one year of follow-up (p=0.0015). Satisfaction Mean overall satisfaction, out of 10 [95% CI] D0 D15 D17 M [ ] 7.8 [ ] 7.6 [ ] 7.5 [ ] Evolution in the whole population Evolution of sub-dimensions of satisfaction in the whole population, over time

17 Satisfaction Satisfaction was not significantly impacted by the addition of CT, nor by a change of strategy! Evolution of overall satisfaction score, according to decisional groups

18 Conclusions - Clinical trial quickly completed: - Very proactive centers; - EndoPredict tests results given within a reasonable time; - Good confidence in the result of the test. - Adendom met its primary objective: Significant change rate = 35.8% of which 7.5% in favor of an addition of chemo and 28.4% of its withdrawal. - The changes essentially contradict the prognostic meaning of SBR grade and KI The EPClin classification of the tumor in good or bad prognosis induces the change of therapeutic strategy.

19 Higher anxiety and distress levels were very significantly correlated with the addition of chemotherapy in the post - EPclin results period. Anxiety and distress returned to baseline levels one year later. In the setting of the present study, the EPclin test is clinically useful but delayed decision should nevertheless be avoided. It seems more acceptable for the patients to receive the treatment strategy in an one-shot announcement.

20 ADENDOM in the landscape of the other impact decision studies

21 EndoPredict Decision Impact Studies Country/City Berlin Munich Clermont-Ferrand Publication/ Conference PlosOne PlosOne SABCS 2016 Year First author Mueller et al. Ettl et al. Penault-Llorca et al. # patients EPclin risk class Low risk 47% 63% 67% High risk 54% 37% 33% Nodal status N0 62% 77% 91% N+ 38% 23% 9% Therapy Change 37.7% 43% 35.8% Net Reduction CT -13.1% -33% -20.9% All studies resulted in a similar proportion of therapy change The 3 studies showed substantial reduction of chemotherapy Copyright 2015 Myriad Genetics, all rights reserved. Myriad.com.

22 International Guidelines Recommendations

23 OUR EXPERIENCE AT CENTRE JEAN PERRIN

24 Technique 2 QA Step 2h 1 RNA Extraction (kit Tissue Preparation Reagents from Sividon) 2h 3 RT-qPCR (Versant kpcr from Siemens) 2h We can run up to 4-5 runs a day Source : endopredict.com

25 ENDOPREDICT CJP UNIRAD study UNIRAD study (started, June ) Objective Evaluation of DFS benefit at 2 years of Afinitor after a standard treatment in ER+ HER2 negative EBC Population Invasive early breast cancer (any T) Primary surgery ER+ HER2 EP clin score patients tested No technical failure 373 pts HIGH RISK (86%) 61 pts LOW RISK (14%) High RISK ER+ HER2 population 86% HIGH RISK

26 ENDOPREDICT EXPERIENCE AT CJP SINCE RIHN 2016 Nbr of cases : 176 High Risk : 88 cases 50% Low Risk : 88 cases 50% 2017 Nbr of cases : 573 High Risk :325 cases 57% Low Risk : 245 cases 43% Failures : 2 cases (low amount of material)

27 EndoPredict Result Report

28 Conclusion : implementation of ENDOPREDICT Easy implementation in the lab Robust test, no failure rates Low amount of tissue required The format allows a great reactivity Great client services