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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