HIGHLIGHTS ESMO 2017 SUPPORTIVE AND PALLIATIVE CARE Florian Scotté MD-PhD Hôpital Foch, Suresnes, France esmo.org
DISCLOSURE SLIDE Consultant / Advisory Boards / Speaker: Tesaro, Sanofi, Roche, MSD, TEVA, Norgine, Prostrakan, Leo pharma, Janssen, Hospira, Boehringer, AMGEN, Pierre Fabre Oncologie, Vifor Pharma Associations: ESMO, ASCO, MASCC, AFSOS, AESCO 2
Prognostic impact of drug interactions in patients with advanced cancer A. Hoemme et al. 1389PD Background: Polypharmacy is the most important risk factor for drug-drug interactions (DDI) Methodology: 3 cohorts: 105 P. with adv. NSCLC, 100 with adv. ER-negative breast cancer (BC), 100 hospice inpatients (HO) with adv. malignancies Collected data: All systemic treatments, age, gender, CNS metastases, smoking status, ECOG-PS, Charlson comorbidity score, overall survival (OS) from the time of incurable cancer Potential DDI were assessed using the Swiss hospindex and a specific DDI software (1) Statistics: Kaplan-Meier, uni- & multivariate Cox regression models Primary study objective: Prognostic value of the severity of DDI per patient cohort ESMO 2017 3
RESULTS The risk of a major DDI increased from 14% in patients with <4 drugs to 24% in patients with 4-7 drugs, 40% with 8-11 drugs and 67% in patients with >11 drugs The severity of DDI was sign. associated with inferior OS in BC (HR=1.34,P=0.018), but not in NSCLC or HO The severity of DDI remained sign. associated with OS in BC (HR = 1.34, P = 0.017) in the multivariate model overall population BC patients Overall survival according to the severity of DDI (figure A) and the number of concurrently administered drugs in the overall population (figure B); Overall survival according to the severity of DDI (figure C) and the number of concurrently administered drugs in BC patients (figure D).
THE SOLUTION Development of an online drug-drug interaction resource to support prescribing of oncolytics N.A.G. Lankheet et al. 1544PD 410 Co-Medications 17% clinically relevant DDI ESMO 2017 5
The effect of cannabis use on tumor response to Nivolumab in patients with advanced malignancies T. Taha et al. 1545PD Retrospective observational study to assess cannabis/immunotherapy interaction NSCLC Melanoma n = 140 NIVOLUMAB (n = 89) NIVOLUMAB + CANNABIS (n = 51) 1st outcome: Response Rate 2 nd outcome: PFS, OS % CR & PR 43,3 45 40 35 30 25 20 15 10 5 33,3 17,6 10 Response rate among patients with OS>=2 months (n=116) p value = 0.016 0 No Cannabis Cannabis No Cannabis Cannabis 42 34 30 10 NSCLC RCC and Melanoma 6
NIVOLUMAB REGIMEN? ESMO 2017 7
UNDER NIVOLUMAB REGIMEN ESMO 2017 8
Open-label randomized study of individualized pharmacokinetically (PK)-guided dosing versus body surface area (BSA) dosing of paclitaxel (PTX) in advanced Non-Small Cell Lung Cancer (NSCLC) NCT02058433 1388 PD Zhang J. et al. Randomized controlled study 1:1 to assess the impact of PK-guided PTX dosing on Safety and Efficacy 4 cycles of 3-weekly carboplatin (AUC=5) plus paclitaxel based on standard BSAguided dosing or PK-guided dosing 1 st endpoint: reduction of grade 4 hematological toxicity 2 nd endpoints: Objective Response (CR, PR, PFS) 275 (86%) Chinese NSCLC patients completed >2 cycles of PC [PTX and carboplatin (AUC 5)] therapy ESMO 2017 9
Dose (cycles 2-4) of PK arm was significantly lower than in the BSA arm: 128 vs. 161 mg/m 2 (p < 0.0001) Lower doses in cycle 4 vs. cycle 1 Exposure based in PK arm: 93% patients dose Toxicity based in BSA arm: 46% patients dose RESULTS BSA dosing results in supratherapeutic PTX exposure After 4 cycles 78% of BSA arm and 18% of PKguided arm (p < 0.001) patients had paclitaxel exposure > target Proportion of Cycles 2-4 with High Grade Neutropenia, Hematological Toxicity or Neuropathy; N=275 Imaging Response (Final Assessment) 10
1387PD D.Martins-Branco Objectives: Define prevalence and recent time trend of ACCEoL comparing metastatic vs non metastatic cancer patients. 92155 patients (01.2010-31.12.2015), male 53.0%, metastatic 14.7%, 14.7% died in a cancer institute. Prevalence of ACCEoL = 71.1%, no clinically meaningful difference Meta vs Non Meta ESMO 2017 11
Clinical Meaningful Variation between Meta and Non Meta (> 5% absolute change in prevalence) ICU Admission Mechanical Ventilation Endotracheal tube insertion ESMO 2017 12
Anticipative approach to improve safety: An innovative Daily Hospital Organisation. Scotté F. et al. 1542-PD the control cohort (2008 period-513 patients). incidence of symptoms reported by grade (NCI-CTC AE: from 0 to 4) Global incidence comparison Mantel-Haenszel khi 2 the on-study cohort (2009-2016 period-3012 patients).
Global Incidence Comparison (p-value according to khi2 test) Adverse Event 2008 (%) 2009-2016 (%) p-value Fatigue 82.4 62.01 <0.0001 Pain 49.69 28.31 <0.0001 Neuropathy 35.77 39.06 0.0784 Nausea 29.92 11.38 <0.0001 Vomiting 8.03 2.26 <0.0001 Infection 7.91 3.48 <0.0001 diarrhea 13.56 7.88 <0.0001 Constipation 34.42 19.28 <0.0001 Dry Skin 38.72 25.21 <0.0001 Hand Foot Syndrome 15.28 2.47 <0.0001 Mucositis 15.54 9.87 <0.0001
The case of Nausea Control Improvement > 10% (21.6%) No adverse event (%) Grade 1-2 (%) Grade 3-4 (%) 2008 70.08 29.32 0.6 2009 79.12 20.57 0.31 2010 85.71 14.07 0.23 2011 87.57 11.87 0.56 2012 89.53 10.39 0.09 2013 90.60 9.36 0.04 2014 90.39 9.61 0.00 2015 90.61 9.39 0.00 2016 91.68 8.23 0.08 p<0.0001 Supportive Care Organisation to be include in CINV guidelines?
FLIE points FLIE points Fosaprepitant reduces the impact of nausea on daily function during five weeks of chemo-radiotherapy - a sub-study of the gand-emesis trial CH Ruhlmann et al. 1540O. Fractioned Radiotherapy n + = 140 CDDP 40mg/m2/w Fosaprepitant + Palonosetron + Steroid (n = 115) Placebo + Palonosetron + Steroid (n = 110) impact on patients daily life of nausea and vomiting (FLIE questionnaire) No emesis during 5 weeks Total Nausea domain 17% difference subhazard ratio 0.58; [95% CI 0.39 0.87]; p=0.008 125 120 115 110 105 p = 0.013 60 p = 0.021 116,3 113,9 FOSAPREPITANT PLACEBO 55 54,9 53.0 50 45 100 End of Study 40 End of Study Ruhlmann et al, Lancet Oncol, 2016;17(4):509-18 ESMO 2017 16
Phase 3 Safety Evaluation of an Intravenous Formulation of NEPA, a Novel Fixed Antiemetic Combination of Fosnetupitant and Palonosetron L.Schwartzberg et al. 1547PD oral NEPA (netupitant 300 mg/palo 0.50 mg) An intravenous formulation of the NEPA fixed combination (fosnetupitant 235 mg/palo 0.25 mg) is under FDA evaluation. Phase 3, multinational, randomized, double-blind, double-dummy, parallel-group study in chemotherapy-naïve patients undergoing non-ac highly emetogenic chemotherapy (HEC) The primary objective: Safety and Tolerability of a single dose of IV NEPA administered with DEX over initial and multiple cycles of HEC. Oral NEPA served as a control. Summary of Adverse Events During Cycle 1 Number (%) patients with IV NEPA (N = 203) Oral NEPA (N = 201) At least one treatment emergent adverse event (TEAE) 120 (59.1%) 135 (67.2%) Severe TEAEs 50 (24.6%) 51 (25.4%) Serious TEAE 29 (14.3%) 21 (10.4%) Any treatment-related TEAE (TRAE) 18 (8.9%) 19 (9.5%) Severe TRAE 1 (0.5%) 2 (1.0%) IV and Oral Same Safety Profil Serious TRAE 0 0 Any TRAE leading to discontinuation 1 (0.5%) 0 Any TRAE resulting in death 0 0 ESMO 2017 17
Evaluation of Antiemetic Practices for Prevention of Chemotherapy-Induced Nausea and Vomiting (CINV): Results of a European Oncology Nurse Study Dielenseger P. et al. 1552P Individual EU Survey to assess; guidelines awareness, practice patterns, perception in CINV / 212 Oncology nurses (16 countries). None Other NCCN MASCC ASCO Antiemetic Guidelines Being Used 7% 8% 16% 25% 27% 0 10 20 30 40 50 47% Barriers/Reasons Interfering with Use of Antiemetic Guidelines Product insurance coverage Complexity of antiemetic regimen Not aware of guideline Satisfied with current antiemetic Patient do not report CINV None 3% 9% 15% 16% 19% 22% Greatest Challenges / Unmet needs: - Delayed CINV : 64% - Impact on QOL : 61% - Acute CINV : 42% Product cost 25% Medication not on formulary 27% Physician preference 39% ESMO 2017 0 5 10 15 20 25 30 35 40 45 18
TAKE HOME MESSAGE Supportive care makes excellent cancer care possible Dorothy M.K. Keefe, past-president of MASCC
PARIS Octobre 2018 Palais Brongniart Paris