pre0065-pluzanski adam - geriatric oncology · 2019. 6. 7. · nk 1 = neurokinin 1 receptor...

17.11.2017

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Adherence to antiemetic treatment

Adam Płużański

Department of Lung Cancer and Chest Tumours,

The Maria Skłodowska-Curie Memorial Oncology Centre and Institute, Warsaw

• Why adherence is important?

• Do I really need the guidelines?

• Guidelines adherence in elderly

Disclosures

Honoraria: Roche, Boeringer Ingelheim, Astra Zeneca, BMS, MSD, Angelini Pharma,

Pierre Fabre

Disclosures

• 70-80% patients receiving chemotherapy

Chemotherapy-induced nausea and vomiting (CINV)

• High risk > 90%

• Moderate risk 30-90%

• Low risk 10-30%

• Minimal risk < 10%

• Depending on onset/duration:

- Acute – onset within 24 h

- Delayed – after > 24 h (usually 3-6 days)

- Anticipatory – before chemotherapy administration

(psychological factor)

(If no prophylaxis)

• Negative impact on QoL

• Dyselectrolytemia

• Dehydration (high risk in elderly!!!)

• May cause dose reduction or treatment discontinuation

Bloechl-Daum B i wsp., J Clin Oncol. 2006;24(27):4472-4478.

Chemotherapy-induced nausea and vomiting (CINV)

Disclosures

CINV- Risk factors

• Sex (females)

• Younger age (< 50 years)

• History of low alcohol and tobacco use

• Motion sickness

• Anxiety

• Nausea/vomiting during pregnancy

• Low performance status

• Polypharmacy

• Comorbidities

• Emetogenic potential of chemotherapy agents

or regimens (Hesketh classification)

• Prior CINV

• Prior exposure for chemotherapy

• Route/dose/frequency

• Use of multiple chemotherapy drugs

Patient related Treatment related

1. Gregory RE, et al. Drugs. 1998;55:173-189

2. Jordan K et al. Oncologist. 2007 Sep;12(9):1143-50.

3. Hesketh PJ, et al. J Clin Oncol. 1997;15:103-109

4. Janelsins MC et al. Expert Opin Pharmacother. 2013 April ; 14(6): 757–766.

.

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Disclosures

CINV - patient health state perception

0,00

0,10

0,20

0,30

0,40

0,50

0,60

0,70

0,80

0,90

1,00

Mucositis

DeathFatigue

Med

ian

Vis

ual A

nalo

gue

Sco

re

Little or No

Nausea or Vomiting

Moderate

Delayed Nausea

Severe

Delayed Nausea

Poorly Controlled

Acute & Delayed CINV

Sun CC, et al. Support Care Cancer. 2005;13:219-227

Disclosures

CINV - patient perception

1. Coates A, et al. Eur J Cancer Clin Oncol. 1983;19:203-208

2. Griffin AM, et al. Ann Oncol. 1996;7:189-195

3. De Boer-Dennert M, et al. Br J Cancer. 1997;76:1055-1061

4. Lindley C, et al. Cancer Pract. 1999;7:59-65

5. Hofman et al, Cancer. 2004 Aug 15;101(4):851-7.

Relevance 19831 19932 19953 19994 20045

1 Vomiting Loss of hair Nausea Nausea Fatigue

2 Nausea Nausea Loss of hair Loss of hair Nausea

3 Loss of hair Constantly tired Vomiting Constantly tired Sleep

Disturbances

4

Thought of

coming for

treatment

Vomiting Constantly tired Vomiting Weight loss

5Length of time

treatment takesIncreased urination

Having to have

an injection

Changes in the

way things tasteLoss of hair

CINV - guidelines

ACUTE Nausea and Vomiting: SUMMARY

EMETIC RISK GROUP ANTIEMETICS

High Non-AC

High AC

Carboplatin

Moderate (other than carboplatin)

Low

Minimal No routine prophylaxis

+

NOTE: If the NK1 receptor antagonist is not available for AC chemotherapy, palonosetron is the preferred 5-HT3 receptor antagonist.

5-HT3 = serotonin3

receptor antagonist

DEX =

DEXAMETHASONE

NK1 = neurokinin1 receptor antagonist:

APREPITANT or FOSAPREPITANT or

ROLAPITANT or NEPA (combination of

netupitant and palonosetron)

DOP = dopamine

receptor antagonist

DEX

DEX

5-HT3

5-HT3

5-HT3

5-HT3

5-HT3

DEX

DEX

DEX

DEX

NK1

NK1

NK1

DOP

+

+

+

or

+

+

+

or

DELAYED Nausea and Vomiting: SUMMARY

EMETIC RISK GROUP ANTIEMETICS

High Non-AC

High AC

Carboplatin

Oxaliplatin,

or anthracycline,or cyclophosphamide

Moderate (other) No routine prophylaxis

Low and Minimal No routine prophylaxis

DEX APRMCP

None

DEXor (if APR 125mg for acute: ( + ) or ( ))

or (if APR 125mg for acute: or )

None or (if APR 125mg for acute: )

DEX APR

APR

DEX can be considered

DEX = DEXAMETHASONE MCP = METOCLOPRAMIDE APR = APREPITANT

+ DEX

Hesketh et al. Bio Med Res IntVolume 2015, 1-12

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Aapro M, et al.Ann Oncol 2014; 25: 1328–1333.

Antiemetic treatment – response rate

Complete response= no emesis, no rescue medication ( 0-120 h).

Effect of Guideline-Consistent TherapyPan European Emesis Registry (PEER)

• 991 patients - 8 European countries

– Austria, Belgium, France, Italy, Spain, Sweden, Netherlands, UK

• Patient outcomes captured using 6-day daily diaries

• Median age-56 yrs

• Assessment of guideline-consistent CINV prophylaxis (GCCP) - based on the MASCC

guidelines

• GICP: guideline-inconsistent CINV prophylaxis

Aapro M, et al. Ann Oncol. 2012;23(8):1986-1992

Only 287/991 patients (29%) received GCCP

- GCCP 11% in HEC


Effect of Guideline-Consistent Therapy (PEER)

CR: complete response; HEC: highly emetogenic chemotherapy; MEC: moderate emetogenic chemotherapy;

GCCP: guideline-consistent CINV prophylaxis ; GICP: guideline-inconsistent CINV prophylaxis


GCCP*

(n=287)

GICP

(n=704)

P value+

Complete Response

(no emesis no rescue med)

172 (59.9%) 357 (50.7%) 0.008

No emesis 182 (63.4%) 412 (58.5%) 0.154

No nausea 138 (48.1%) 286 (40.6%) 0.031

No CINV 122 (42.5%) 242 (34.4%) 0.016

Effect of Guideline-Consistent Therapy (PEER)- response rate

0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

GP Visit Specialist Visit ER Visit Hospital Days

per 100 patients

GCCP (n=287)

GICP (n=704)

Aapro, Ann Oncol 23:1986, 2012

GCCP=guideline-consistent prophylaxis; GICP=guideline-inconsistent prophylaxis

Health Care Resource Utilization

Health care visits to manage CINV over 5 days after initiation of chemotherapy

Total visits:

5%

7,4%

Non adherence

N %

HEC – GICP 168 100%

Day 1

Dexamethasone 141 83.9%

NK1-RA 87 51.8%

5HT3-RA 159 94.6%

Day 2


NK1-RA 68 40.5%

Day 3


NK1-RA 70 41.7%

Day 4


N %

MEC - GICP 206 100%

Day 1


5HT3-RA 193 93.7%

Day 2

Dexamethasone

or 5HT3-RA 61 29.6%

Day 3

Dexamethasone

or 5HT3-RA 13 6.3%

non-prescribing of corticosteroid and NK1-RA

(delayed phase)

Non-prescribing of NK1-RA (acute phase and

overuse of corticosteroid and/or 5HT3-RA

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• Potential issues:

- metabolism (decline in liver and renal function, )

- polypharmacy- drug-drug interaction

Efficacy of antiemetic treatment in elderly

Chapell R., Aapro M. JGO 2013:4;78:-83


3 drug regimen in HEC:

- 5HT3+NK1 RA+ Dex

Hesketh et al. Bio Med Res Int Vol. 2015, 1-12


NEPA- netupitant+palonosetron - more efficient in elderly

NEPA- randomized clinical trials

• If adherence to guidelines is equal then response is equal

E. Massa et al. Critical Reviews in Oncology/Hematology 70 (2009) 83–91

Efficacy of antiemetic treatment in elderly vs younger

1. Grunberg SM, et al. Cancer. 2004;100:2261-8.

HEC: highly emetogenic chemotherapy; MEC: moderately emetogenic chemotherapy; RN: Registered nurse; MD: Physician.

MECHEC

0

10

20

30

40

50

60

70

34 33

17

12

39

60

22

50

24

37

13 13

24

52

15

28Pa

tie

nts

(%)

MD/RN Prediction

Patient Experience

Acute

nausea

Acute

vomiting

Delayed

nausea

Delayed

vomiting

Acute

nausea

Acute

vomitingDelayed

nausea

Delayed

vomiting

HEC MEC

CINV - physician`s wishful thinking

* Patient-reported symptoms were collected directly from 467 persons with different malignant conditions at a total of 4034 clinic visits at

Memorial Sloan-Kettering Cancer Center, New York

** Clinician-reported symptoms were recorded by physicians and nurses treating those patients at the same visits

Basch E. NEJM 2010;362(10):865-9

Months Months

CINV – reporting bias in „real life”

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Di Maio M et al. Journal of Clinical Oncology, 2015; 33:910-915.

ELDA, Elderly Breast Cancer—Docetaxel Adjuvant: randomly assigned to receive AC or Docetaxel treatments;GECO, Gemcitabine–Coxib (in NSCLC) randomly assigned to receive Gemcytabin or cisplatin;

TORCH, Tarceva or Chemotherapy (in NSCLC) randomly assigned to receive Cisplatin or Erlotinib

CINV – reporting bias in randomized clinical trials

Under-reporting was calculated as rate of cases where

physicians reported grade 0 toxicity in all cycles, of cases

where patients reported toxicity in grade ≥1

Proportion of under-reporting by physicians

• Lack of prospective trials or even reports

• Guidelines (drug prescribed to take at home - days 2-4)

- compliance: studies have reported that 25–59% of the elderly do not take drugs as prescribed

- non-compliance risk increased with: number of medications, dementia, impaired vision etc.

- living alone – if no caregiver

Guidelines adherence in elderlyPotential issues

• Steroids (delayed nausea and vomiting) - 8-12mg/day

• Adverse events in elderly:

- insomnia, euphoria, gastric bleeding (increased risk with NSAIDs), hyperglycemia


Adverse events of antiemetic drugs

Serotonin-5-(HT)3-receptor antagonists

Schwartzbergn L. et al. Support Care Cancer (2014) 22:469–477

• Palonosetron vs granisetron/ondansetron/dolasetron

QTc interval prolongation 2%

(5-HT3 RA - dose dependend)

Gralla R. et al.,Annals of Oncology 25: 1333–1339, 2014

NEPA and NK1 receptor antagonists

Hesketh et al. Bio Med Res Int Volume 2015, 1-12

• Treatment related AE - 8-15%

• constipation, headache


co-morbidity symptom Antiemetic drug

Heart disease prolongation QTc interval 5HT3- RA

Diabetes hyperglicemia steroids

Gastrointestinal disorders constipation

Bleeding

steroids

Neurological

syndromes/epilepsy

Convulsion metoclopramide

Impact of antiemetic AE on co-morbidity

Co-morbidities can increase risk of toxicity and limit patients’ compliance

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• Efficacy of standard CINV prophylaxis is equal or better than in younger

• Proper risk assessment - including patient related risk factors and comorbidities

1. Burke TA, et al. Support Care Cancer. 2011;19:131–40.

2. Kosimbei G, et al. Health Res Policy Syst. 2011;9:24.

How to adhere to antiemetic treatment in elderly

Dranitsaris G et al., Ann Oncol 2017

• Efficacy of standard CINV prophylaxis is equal or better than in younger

• Proper risk assessment- including patient related risk factors and comorbidities

• Guidelines in elderly should be followed but adherence monitored closely

• Risk of non-adherence and adverse consequences such as dehydration and renal impairment is

higher due to comorbidities




http://www.mascc.org/assets/Guidelines-Tools/mat_english_questionnaire_2010_2.pdf

Collecting information about compliance, symptoms and rescue medication


• Efficacy of standard antiemetic CINV prophylaxis is equal or better than in younger

• Proper risk assessment- including patient related risk factors and comorbidities

• Guidelines in elderly should be followed but adherence monitored closely

• Risk of non-adherence and adverse consequences such as dehydration and renal impairment is

higher due to comorbidities

• Patients with emesis may require emergency care or hospitalization, adding additional burden to

cancer care



How to adhere to antiemetic treatment in elderlyUnexpected CINV episode management

• increase of the originally prescribed antiemetic

dosage/drugs

• rehydration

• laboratory tests

• hospitalization/ER admission

• ambulance transportation

• Increased cost/patient - 389-1016 EUR

Turini M et al. Drugs in Context 2015; 4: 212-285

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Conclusion

patient

antiemetic prophylaxis

Pro

pe

r ri

sk a

sse

ssm

en

t

Co

mp

lia

nce

an

d m

on

ito

rin

g

Gu

ide

lin

e d

rive

n t

he

rap

ycomunication

physician caregiver

patient

Thank you

pre0065-pluzanski adam - geriatric oncology · 2019. 6. 7. · nk 1 = neurokinin 1 receptor...

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