ESMO HIGHLIGHTS SUPPORTIVE AND PALLIATIVE CARE

Transcription

1 ESMO HIGHLIGHTS SUPPORTIVE AND PALLIATIVE CARE FLORIAN SCOTTE Cancer Department Supportive Care in Cancer Unit Georges Pompidou European Hospital Paris France esmo.org

2 DISCLOSURE SLIDE Consultant / Advisory Boards / Speaker : Sanofi, Roche, MSD, TEVA, Norgine, Prostrakan, Leo pharma, Janssen, Hospira, Boehringer, AMGEN, Pierre Fabre Oncologie, Vifor pharma. Associations: ESMO, ASCO, MASCC, AFSOS, AESCO.

3 IDENTIFYING CANCER PATIENTS AT HIGH RISK FOR CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING (CINV): THE DEVELOPMENT OF A PREDICTION TOOL Objectives: 1. To identify risk factors associated with grade 2 CINV 2. To develop a prediction model for grade 2 CINV to identify high-risk patients prior to each cycle of therapy 3. To develop a numerical risk algorithm system Methods: 1. Prospectively collected data from 1198 patients who received 4197 cycles of chemotherapy 2. Risk factors with a p-value < 0.05 following a chemotherapy cycle were retained and included in a generalized estimating equations (GEE) regression analysis 3. A risk scoring algorithm (range: 0-32) derived from the final model coefficients was then developed 4. The predictive accuracy of the risk algorithm system was determined via a receiver operator characteristic (ROC) curve analysis ESMO Dranitsaris G et al. Abs PD

4 PREDICTIVE RISK FACTORS AND PREDICTION TOOL FOR CINV Start at base score of 10 Predictive Factor Odds Ratio Impact on CINV Risk Scoring Algorithm Patient age If patient aged < by 41% + 1 Expectation If patient expects to have CINV 1.41 by 41% + 1 Sleep If patient slept less than 7 hours the night before chemo 1.34 by 34% + 1 Morning sickness If patient has positive history of morning sickness 1.30 by 30% + 1 Chemotherapy If patient is about to receive platinum or anthracyclines 1.94 by 94% + 2 Prior CINV If patient had nausea or vomiting in the prior cycle 5.17 by 5.17 times + 5 Antiemetic use at home If non-rx antiemetics are used at home 2.70 by 2.7 times + 3 Cycle If 2nd cycle of chemotherapy If 3rd cycle by 83% by 85% 5 6 Total score ESMO Dranitsaris G et al. Abs PD

5 ACCURACY OF THE PREDICTION MODEL & CINV RISK VS RISK CATEGORY Risk Category Score cut point CINV incidence* Sensitivity Specificity Likelihood ratio 1 < % 100% 0% to < % 99.8% 1.2% to < % 97.9% 10.7% to < % 87.4% 38.4% to < % 51.2% 75.7% to < % 18.8% 94.8% % 2.1% 99.8% 9.08 *As observed in the patient sample Patients with a total score 16 are considered at high risk of CINV Moving from one scoring category to another increases CINV risk by 80% (OR = 1.80; p < 0.001) ESMO Dranitsaris G et al. Abs PD

6 ONCOLOGY NURSES SURVEY : IMPACT OF EMESIS ON EMERGENCY DEPARTMENT AND TREATMENT DISRUPTION ESMO Rittenberg C et al. Abs.1444P

7 EXPLORATION OF THE HETEROGENEITY OF MODERATELY EMETOGENIC CHEMOTHERAPY ON RESPONSE TO FOSAPREPITANT IN A RANDOMIZED PHASE III TRIAL Day 1 Fosaprepitant Regimen Ondansetron PO q8h Dexamethasone PO Fosaprepitant IV Control Regimen Ondansetron PO q8h Dexamethasone PO Placebo IV Days 2 3 Placebo PO q12h Ondansetron PO q12h Primary end point : efficacy CR = No vomiting and no use of rescue medication Delayed phase = hours following first dose of MEC To explore factors that may impact CR, including MEC heterogeneity (carboplatin vs non-carboplatin) ESMO C. Weinstein et al. Abs 14350

8 OVERALL CHEMOTHERAPY DISTRIBUTION (ITT POPULATION, N = 1000) Heterogeneity of Moderately Emetogenic Chemotherapy (MEC) Broad Range for Risk of Emesis: 30-90% Carboplatin Population is split approximately equally between carboplatin and non-carboplatin regimens 11.5% 23.9% 51.3% Oxaliplatin Cyclophosphamide Doxorubicin Other Irinotecan Epirubicin Bendamustine Ifosfamide Data reflect cycle 1; only the first dose of MEC or other (non-mec) agents is displayed ESMO C. Weinstein et al. Abs

9 RESULTS OF PRIMARY ANALYSIS: MEC PN 031 Complete Response (CR), Delayed Phase, absolute difference: 10.4 % (P < 0.001) P = Proportion of Subjects, % P < P < CR Acute Phase CR Delayed Phase* CR Overall Phase Fosaprepitant Control *Primary end point. Based on Cochran-Mantel-Haenszel method with stratification by sex. Weinstein C et al. Ann Oncol. 2016;27: ESMO C. Weinstein et al. Abs

10 COMPLETE RESPONSE BY CHEMOTHERAPY TYPE Fosaprepitantyields a consistent CR rate (76-80%) in carboplatin and non-carboplatin delayed and overall phases Proportion of Subjects, % ACUTE PHASE DELAYED PHASE OVERALL PHASE Carbo Non-Carbo Carbo Non-Carbo Carbo Non-Carbo N Fosaprepitant Control ESMO C. Weinstein et al. Abs

11 NK1-RA REGIMENS IN SUBJECTS RECEIVING CARBOPLATIN Fosaprepitant shows a similar absolute difference in Complete Response Aprepitant COMPLETE RESPONSE Overall Phase (0-120 h) NK1RA + 5-HT 3 RA + DEX, % 5-HT 3 RA + DEX, % Absolute Difference, % Tanioka (N = 91) a Br J Cancer Ito (N = 134) Lung Cancer Yahata (N = 324) b Int J Clin Oncol Rolapitant Hesketh (N = 401) c Cancer Fosaprepitant Weinstein (N = 513) d Adapted from Jordan K et al, Annals of Oncology a 98% patients with carboplatin-based chemotherapy. b All patients with carboplatin and paclitaxel. c Post hoc analysis Schwartzberg study. d Randomized controlled trial. NK1RA = neurokinin-1 receptor antagonists 5HT3 RA = serotonin receptor antagonists DEX = Dexamethasone ESMO C. Weinstein et al. Abs Jordan K et al. Ann Oncol. 2015;26:

12 ...UPDATE THE ANTIEMETICS GUIDELINES Jordan K et al. Ann Oncol / Educational Session ESMO 2016

13 ACUTE Nausea and Vomiting: SUMMARY 13 EMETIC RISK GROUP ANTIEMETICS High Non-AC 5-HT 3 + DEX + NK 1 High AC 5-HT 3 + DEX + NK 1 Carboplatin Moderate (other than carboplatin) 5-HT 3 5-HT DEX DEX + NK 1 Low 5-HT 3 or DEX or DOP Minimal No routine prophylaxis 5-HT 3 = serotonin 3 receptor antagonist DEX = DEXAMETHASONE NK 1 = neurokinin 1 receptor antagonist such as APREPITANT or FOSAPREPITANT or ROLAPITANT or NEPA DOP = dopamine receptor antagonist NOTE: If the NK 1 receptor antagonist is not available for AC chemotherapy, Palonosetron is the preferred 5-HT 3 receptor antagonist. ESMO Jordan K. et al. Oral educational Session

14 DELAYED Nausea and Vomiting: SUMMARY 14 EMETIC RISK GROUP High Non-AC High AC DEX None ANTIEMETICS or (if APR 125mg for acute: ( MCP + DEX ) or APR ) or (if APR 125mg for acute: DEX or APR ) Carboplatin Oxaliplatin, or Anthracycline, or Cyclophosphamide Moderate (other) None or (if APR 125mg for acute: APR ) DEX can be considered No routine prophylaxis Low and Minimal No routine prophylaxis DEX = DEXAMETHASONE MCP = METOCLOPRAMIDE APR = APREPITANT 2016 V.1.1 ESMO Jordan K. et al. Oral educational Session

15 Use of chemotherapy near the end of life for solid cancers: What factors matter? Philippe Rochigneux 1, Jean-Luc Raoul 1, Lucas Morin 2 1 : Paoli-Calmettes Cancer Center, Marseille, France 2 : Karolinska Institutet, Stockholm, Sweden ESMO Rochigneux P. et al. Abs 13000

16 A French hospital-based register January 2010 December ,244 Hospitalized cancer decedents Study Flow Chart Excluded Main analysis: n=279,846 patients Multivariate analysis of associated factors : patient-level : age, sex, comorbidity tumor-level : localization facility-level : category, size, palliative care unit 32,212 patients with brain or liver cancer 431,369 Potentially eligible individuals 399,157 patients with other solid tumors 58,292 patients with hematological malignancies 26,583 patients with overlapping primary malignancies Sub-analysis: n = 182,938 patients 1. Chemosensitivity? 2. Median expected overall survival? 3. Therapeutic innovation? 279,846 patients included in the main analysis Excluded 151,523 without diagnosed distant metastases Chemotherapy or targeted therapy over the last 3 months of life 182,938 patients included in sub-analyses (26 specific tumor sites) ESMO Rochigneux P. et al. Abs 13000

17 Frequency of chemotherapy near EOL MAIN ANALYSIS : n= 279,846 patients France, , all types of hospitals Last three Last two Last Last two Last months months month weeks week Total study population 39.1% 32.0% 19.5% 11.3% 7.0% Chemotherapy rates Chemotherapy rates ESMO Rochigneux P. et al. Abs 13000

18 Factors associated with chemotherapy use (last month) SUB-ANALYSIS: n=182,938 patients N total Chemo last month Multivariate Analysis N = % OR (95%CI) Median overall survival <12 months 75,849 13, % 1 12 to 24 months 71,929 11, % 0.98 (0.95 to 1.00) > 24 months 35,160 9, % 1.37 (1.32 to 1.42) Therapeutic innovation ( ) No 80,780 13, % 1 Yes 102,158 21, % 1.17 (1.14 to 1.20) Chemosensitive tumor No 69,867 11, % 1 Yes 113,071 23, % 1.21 (1.18 to 1.25) ESMO Rochigneux P. et al. Abs 13000

19 ESMO Waller C. et al. Abs 14330

20 Breast Cancer patients Adjuvant TAC (Doc 75, A 50, C 500 D1-D21) CT cycle N=194 R 2:1 Peg-GCSF injection MYL 1401H 6 mg SC EU-NEULASTA 6 mg SC N=127 N=67 Assessment: - Duration severe neutropenia (ANC< /l) - Efficacy equivalence 95% CI [- 1; +1 Days] - Safety observation 24 w after 1st study drug administration Primary Endpoint : Equivalence mean +/- SD = 1.2 +/- 0,93 vs 1.2 +/ MYL 1401H vs Neulasta 95% CI of least squares mean difference: [-0.285d; 0.298d] within [-1; +1 days] range Secondary Endpoints: Equivalence in safety ESMO Waller C. et al. Abs 14330

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22 Multicenter questionnaire to 104 professionaly active patients 8-10 months after diagnosis BACK TO WORK To identify factors influencing return to work. P=0.003 P=0.006 P=0.018 P=0.008 P=0.009 ESMO Adam N et al. Abs 1353P

23 A PHASE 3 STUDY: NALDEMEDINE TO TREAT OPIOID INDUCED CONSTIPATION Peripheral Acting µ opioid receptor antagonist Cancer patients Stable opioids > 2 w Laxative insufficient N=190 R 1:1 NALDEMEDINE 0.2 mg QD n=83 2w treatment+ 4w followup PLACEBO QD n=88 SBM CSBM SBM=Spontaneous Bowel Movement CSBM=SBM + complete evacuation feeling Median time to BM after the initial dose (hour, 95% CI) Naldemedine 0.2 mg N= (3.00, 7.58) Placebo N= (19.65, 58.17) Naldemedine 0.2 mg N= (9.00, 43.25) P value < < Placebo N= (117.75, -) ESMO Toru Murata et al. Abs 1466P

24 Patient Caregivers Health Care Professionals Doctors / Nurses / HC Assistants WE ARE FAMILY F.Strasser. Poster Discussion Session

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