HIGHLIGHTS ESMO 2017 SUPPORTIVE AND PALLIATIVE CARE

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1 HIGHLIGHTS ESMO 2017 SUPPORTIVE AND PALLIATIVE CARE Florian Scotté MD-PhD Hôpital Foch, Suresnes, France esmo.org

2 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

3 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

4 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).

5 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

6 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 17,6 10 Response rate among patients with OS>=2 months (n=116) p value = No Cannabis Cannabis No Cannabis Cannabis NSCLC RCC and Melanoma 6

7 NIVOLUMAB REGIMEN? ESMO

8 UNDER NIVOLUMAB REGIMEN ESMO

9 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) NCT 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

10 Dose (cycles 2-4) of PK arm was significantly lower than in the BSA arm: 128 vs. 161 mg/m 2 (p < ) 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

11 1387PD D.Martins-Branco Objectives: Define prevalence and recent time trend of ACCEoL comparing metastatic vs non metastatic cancer patients patients ( ), 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

12 Clinical Meaningful Variation between Meta and Non Meta (> 5% absolute change in prevalence) ICU Admission Mechanical Ventilation Endotracheal tube insertion ESMO

13 Anticipative approach to improve safety: An innovative Daily Hospital Organisation. Scotté F. et al 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 ( period-3012 patients).

14 Global Incidence Comparison (p-value according to khi2 test) Adverse Event 2008 (%) (%) p-value Fatigue < Pain < Neuropathy Nausea < Vomiting < Infection < diarrhea < Constipation < Dry Skin < Hand Foot Syndrome < Mucositis <0.0001

15 The case of Nausea Control Improvement > 10% (21.6%) No adverse event (%) Grade 1-2 (%) Grade 3-4 (%) p< Supportive Care Organisation to be include in CINV guidelines?

16 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 ]; p= p = p = ,3 113,9 FOSAPREPITANT PLACEBO 55 54, End of Study 40 End of Study Ruhlmann et al, Lancet Oncol, 2016;17(4): ESMO

17 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

18 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% % 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

19 TAKE HOME MESSAGE Supportive care makes excellent cancer care possible Dorothy M.K. Keefe, past-president of MASCC

20 PARIS Octobre 2018 Palais Brongniart Paris

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