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esmo.org
HIGHLIGHTS ESMO 2017
SUPPORTIVE AND PALLIATIVE CARE
Florian Scotté MD-PhD
Hôpital Foch, Suresnes, France
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
ESMO 2017 3
Prognostic impact of drug interactions in patients with advanced cancerA. 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
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 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).
overall population BC patients
Development of an online drug-drug interaction resource to support prescribing of oncolytics
N.A.G. Lankheet et al. 1544PD
ESMO 2017 5
410 Co-Medications
17% clinically relevant DDI
THE SOLUTION
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
6
0
5
10
15
20
25
30
35
40
45
CannabisNo CannabisCannabisNo Cannabis
10303442
RCC and MelanomaNSCLC
10
43,3
17,6
33,3
% CR & PR
Response rate among patients with OS>=2 months
(n=116)p value = 0.016
NSCLCMelanoma
NIVOLUMAB(n = 89)
NIVOLUMAB + CANNABIS(n = 51)
1st outcome: Response Rate2nd outcome: PFS, OS
n = 140
ESMO 2017 7
NIVOLUMAB REGIMEN
?
ESMO 2017 8
UNDER NIVOLUMAB REGIMEN
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 BSA-guided dosing or PK-guided dosing
• 1st endpoint: reduction of grade 4 hematological toxicity
• 2nd 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
RESULTS
Proportion of Cycles 2 - 4 with High Grade Neutropenia, Hematological
Toxicity or Neuropathy; N=275 Imaging Response (Final Assessment)
10
► Dose (cycles 2-4) of PK arm was significantly lower
than in the BSA arm: 128 vs. 161 mg/m2 (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
► BSA dosing results in supratherapeutic PTX
exposure
► After 4 cycles 78% of BSA arm and 18% of PK-
guided arm (p < 0.001) patients had paclitaxel
exposure > target
• Objectives: Define prevalence and recent time trend of ACCEoL comparing metastaticvs 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
1387PD D.Martins-Branco
ESMO 2017 12
Clinical Meaningful Variation
between Meta and Non Meta
(> 5% absolute change in
prevalence)
ICU Admission
Mechanical Ventilation
Endotracheal tube insertion
the control cohort (2008 period-513 patients).
the on-study cohort (2009-2016 period-3012 patients).
Global incidence comparison
Mantel-Haenszel khi2
incidence of symptoms reported by grade
(NCI-CTC AE: from 0 to 4)
Anticipative approach to improve safety: An innovative Daily Hospital Organisation.
Scotté F. et al. 1542-PD
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
No adverse event (%)
Grade 1-2 (%) Grade 3-4 (%)
2008 70.08 29.32 0.6
p<0.0001
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
Improvement > 10%(21.6%)
Supportive Care Organisation to be include in CINV guidelines?
ESMO 2017 16
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.
Ruhlmann et al, Lancet Oncol, 2016;17(4):509-18
FractionedRadiotherapy +CDDP 40mg/m2/w
Fosaprepitant+ Palonosetron + Steroid
(n = 115)
Placebo+ Palonosetron + Steroid
(n = 110)
impact on patients’ daily lifeof nausea and vomiting
(FLIE questionnaire)
n = 140
17% difference
subhazard ratio 0.58;
[95% CI 0.39–0.87]; p=0.008
No emesis during 5 weeks
116,3113,9
100
105
110
115
120
125
End of Study
FLIE
po
ints
Total
FOSAPREPITANT
PLACEBO
54,953.0
40
45
50
55
60
End of Study
FLIE
po
ints
Nausea domain
p = 0.013 p = 0.021
ESMO 2017 17
Phase 3 Safety Evaluation of an Intravenous Formulation of NEPA, a Novel
Fixed Antiemetic Combination of Fosnetupitant and PalonosetronL.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%)
Serious TRAE 0 0
Any TRAE leading to discontinuation 1 (0.5%) 0
Any TRAE resulting in death 0 0
IV and OralSame Safety Profil
Evaluation of Antiemetic Practices for Prevention of Chemotherapy-InducedNausea and Vomiting (CINV): Results of a European Oncology Nurse Study
Dielenseger P. et al. 1552P
• EU Survey to assess; guidelines awareness, practice patterns, perception in CINV / 212 Oncology nurses (16 countries).
ESMO 2017 18
0 10 20 30 40 50
Individual
ASCO
MASCC
NCCN
Other
None
Antiemetic Guidelines Being Used
47%
27%
25%
16%
8%
7%
0 5 10 15 20 25 30 35 40 45
Physician preference
Medication not on formulary
Product cost
None
Patient do not report CINV
Satisfied with current antiemetic
Not aware of guideline…
Complexity of antiemetic regimen
Product insurance coverage
Barriers/Reasons Interfering with Use of Antiemetic Guidelines
39%
27%
25%
22%
19%
16%
15%
9%
3%
Greatest Challenges / Unmet needs:- Delayed CINV : 64%- Impact on QOL : 61%- Acute CINV : 42%
“Supportive care makes excellent cancer care possible”
“Dorothy M.K. Keefe, past-President of MASCC
TAKE HOME
MESSAGE
PARIS Octobre 2018Palais Brongniart
Paris