Too little, too late Real World Insights on Current ... · Real World Insights on Current Practice . of Home Parenteral Nutrition in Germany. ESMO 2018, Munich. Prof. Dr. med. Ingolf

Too little, too late Real World Insights on Current Practice

of Home Parenteral Nutrition in Germany

ESMO 2018, Munich

Prof. Dr. med. Ingolf Schiefke

Gastroenterology and Hepatology Klinikum St. Georg gGmbH

Leipzig, Germany

1

Agenda

2

Introduction parenteral nutrition

Objectives

Methodology

Results Demography Comorbidities Clinical outcomes: Survival Drug costs utilisation

Summary

Conclusions

3

Nutrition SupportVolume 38 Number 2

Original Communication

Adapted from Hbuterne X, et al. JPEN J Parenter Enteral Nutr. 2014;38:196-204.

Prevalence of Malnutrition and Current Use of Nutrition

4Arends J, et al. Clin Nutr. 2017;36(1):11-48.

ESPEN Guidelines on Nutrition in Cancer Patients (1)

5Arends J, et al. Clin Nutr. 2017;36(1):11-48.

ESPEN Guidelines on Nutrition in Cancer Patients (2)

6

*Includes values of arm circumference, triceps skinfold, albumin and transferrin normal values

7

Cancer-specific Survivals

Progression-freeSurvivals

Disease-freeSurvivals

Shachar SS, et al. Eur J Cancer. 2016;57:58-67.

Sarcopenia is a prognostic markerHazard Ratios for:

8

No Yes

Grade 3-4 Toxicity

Skel

etal

Mus

cle

Gau

ge(S

MG

)

2,500

2,000

1,500

1,000

500

P=0.04

Shachar SS, et al. Clin Cancer Res. 2017;23(3):658-665

Toxicity from Taxane in Breast Cancer Patients with Sarcopenia

Study Objectives

9

This study1 is set out to investigate real-world use of home parenteral nutrition (HPN) amongst cancer patients with 5 tumour types in Germany.

The study quantified the number of deceased cancer patients who received HPN

Data analysis described

1)patients demographic characteristics

2)patients comorbidities

3)clinical outcomes of patients who received PN

Additional data analysis provided an indication of cost share between cancer treatment and parenteral nutrition across 5 tumour types.

1) Data on file: Versorgungsforschung zur parenteralen Ernhrung in Deutschlang in Zusammenarbeit HGC GesundheitsConsult GmbH, 2017

Observation window is 6 yearsBasic data

Age GenderRegion

Outpatient treatmentUtilization (EBM Figures)Diagnoses (ICD codes)Physicians

Inpatient treatmentHospital stays (DRG, OPS)Diagnoses (ICD)Length of stay

Pharmaceutical dataATC, PZNDDDPrescriptions/ prescriber

Treatment via medical devices medical aids, remedies

Disability and sick payCosts and resource use

Available SHI claims data

Long

itudi

nal P

atie

nt D

ata~4 million insured

individuals~70 Statutory

Health Insurances 5.5% nationwide

representative sample

10

Study Content Methodology (1)

There is a good overall accordance of the Health Risk Institute database and the German population in terms of measures of morbidity, mortality and drug usage.

Persistence of insurant with the database over time is high, indicating suitability of the data source for longitudinal epidemiological analyses1.

External validity of database

1 Andersohn, F; Walker, J (2016), Characteristics and external validity of the German Health Risk Institute (HRI) Database2 Swart, E et. al (2014), Gute Praxis Sekundrdatenanalyse (GPS): Leitlinien und Empfehlungen

The analysis has been designed following the Good Practice in Secondary Data Analysis (GPS) 2

The 11 guidelines range from ethical principles and study planning through quality assurance measures and data preparation to data privacy, contractual conditions and responsible communication of analytical results.

Validity of Methodology

Valid

ity o

f dat

aset

11


The study population was defined as deceased stage IIIb/ IV cancer patients

Five cancer types were included ovarian, pancreas, colorectal carcinoma (CRC), gastric, head & neck (H&N); defined regarding to ICD 10 GM Coding Chapter C (confirmed outpatient or inpatient diagnoses)

Observation period was defined as period between initial therapy of Stage IIIb/IV cancer until day of death

Definition of initial treatment to identify Stage IIIb/IV patients (metastatic or recurrent carcinoma)

Definition of home parenteral nutrition based on prescriptions (Pharmacy Registration Number) in the outpatient sector

12

We observed deceased Stage IIIb/IV cancer patients with or without home parenteral nutrition (HPN)


Deceased cancer patients Stage IIIb/IV

Index Day of death/

calendar quarterIndividual observation period

Index Quarter in which the initial

therapy pursuant to guidelines of stage IV

cancer started

13

Head & NeckCetuximab

without radiation

CRCBevacizumab or

Cetuximab

OvarianCarboplatin and Paclitaxel

and/or Bevacizumab

Gastricdiagnosis, directly followed by prescription of parenteral

or enteral nutrition

PancreaticGemcitabin, if there was no surgery 3

months before


20122011 2013 2014 2015 2016

14

Maximum

Minimum

MedianMean

0

20

40

60

80

100

Head & Neck CRC Ovarian Gastric

95 y

71.6 y

21 y

92 y

69.9 y

33 y

85 y

63.4 y

26 y

93 y

67.0 y

23 y

88 y

62.9 y

27 y

SD:10,1SD:11 SD:11,1 SD:9,7

SD:12,6

Age per cancer indication / age at pick up stage IIIb/IV

Pancreatic

Mean age of the patients at 1st line cancer treatment is 67 years with a higher share of male patientsH&N CRC Ovarian Pancreas Gastric

No HPN 300 1,675 228 1,197 447

HPN 43 290 53 209 153

H&N CRC Ovarian Pancreas GastricM (%) 83.4 62.8 - 57.3 63.7F (%) 16.6 37.2 100 42.7 36.3

Gender distribution

Study Content Demographics (1)

The number of HPN users differs substantially in each cancer group

Head & Neck

43 300

HPN No HPN

Number of patients in DB*1(cancer all stages)Indexing period: Date of death between 2010-16No multiple cancer diagnosesIndexing: 1st line patients and no previous HPN*2

Number of patients with or without HPN

290 1,675

HPN No HPN

53 228

HPN No HPN

209 1,197

HPN No HPN

153 447

HPN No HPN

CRC Ovarian GastricPancreatic

*1 The total database (DB) comprises data of 4 million insured individuals per year*2 initial therapy pursuant to guideline of Stage IV cancer (metastatic or recurrent carcinoma) 15

19,313

6,027

5,437

343

53,390

19,574

17,742

1,966

8,900

3,353

2,765

281

10,143

7,633

6,784

1,406

12,480

6,783

5,716

600

Study Content Demographics (2)

Share of patients with / without PN per cancer indication

Share of patients with HPN Share of patients without HPN

H&N CRC Ovarian Pancreatic Gastric

The share of patients with HPN in overall cancer types is on average 16% The highest share of HPN patients is observed in patients with Gastric cancer at 25% (153

out of 600). The lowest share of HPN patients is observed in patients with Head & Neck cancer at 12%

(43 out of 343). Caveat: Enteral nutrition therapy is not covered within this analysis

43 290 53 209153

300 1676 228 1197447

0%

20%

40%

60%

80%

100%

12% 15% 15%19% 25%

16

Study Results Demographics (1)

61%71%

14%21%

28%37%37% 38%

10% 11%

27%16%

0%

20%

40%

60%

80%

100%

Year 1 Year 2 Year 1 Year 2 Year 1 Year 2

Cachexia Infection With at least one of definedcomorbidities*

PN No PN

Up to 40% of the gastric cancer patients suffering from cachexia are not treated with HPN

Share of Gastric cancer patients with comorbidities

17

Only 2 years of observation. Third follow-up year n

Share of Gastric cancer patients with Decubitus vs. no Decubitus (in year 1)

22%

78%

without HPN

Dekubitus

No Dekubitus

12%

88%

with HPN

The share of patients with decubitus is higher in year 2 compared to year 1, especially for patients with HPN

That indicates a physical decline in patients with HPN Patients without HPN suffer less from decubitus in year 2

18

Year 1 Year 2 Year 3 Year 4 Year 5 Year 6Patients with PN 124 38 11

376.7days

295.7days

Mean period until death per patient without HPN in days

472.4days

718.8days

209.3days

237.7days

+ 81 d + 29 d + 41 d + 84 d + 118 d HPN - No HPNMean period until death per patient withHPN in days

500.7days

760.1days

292.9days

355.5days

The longest mean period until death per patient without HPN is observable in Ovarian cancer patients (~2 years)

The biggest difference in the period until death between HPN and no HPN can be seen in Gastric patients (+118 days)

The period between start HPN and death amounts is around 3 months, which is too late according to the definition of refractory cachexia

Overview of average duration until death per patient in each cancer indication

H&N CRC Ovarian Pancreas Gastric

No HPN 300 1,675 228 1,197 447

HPN 43 290 53 209 153

19

Data suggests that patients receiving HPN survive on average 70 days longer than patients not receiving HPN (caveat: descriptive readout only)

Study Results Survival (1)

Head & Neck CRC Ovarian GastricPancreatic

The longest average period until HPN initiation per patient is observable in Ovarian cancer patients ~ 2 yrs

The shortest average period until HPN initiation per patient is observable in Gastric cancer patients ~ 6 mos

Head & Neck CRC Ovarian GastricPancreaticAverage duration until PN initiation per patient in days

266.6days

394.5days

625.8days

200.1days

195.7days

Average period until PN initiation per patient in each cancer indication


No HPN 300 1,675 228 1,197 447

HPN 43 290 53 209 153 20

H&N CRC Ovarian GastricPancreatic

The time from initiation of cancer treatment to initiation of HPN varied widely by cancer indication, with on average of 1 year (337 days) delay


Diagramm1

H&N

CRC

Ovarial-CA

Pankreas

Magen

266.6

394.5

625.8

200.1

195.7

Job 1 - Means

time to PE, Time to death, time from PE until to death, by PE-Type ( days)Fischoel

gruppetypeVariableMinimumMittelwertMedianMaximumStd.abweichungH&NCRCOvarial-CAPankreasMagengesamt

halskopfFischoeldauerbispedauerbistotdauerpebistot0.009.002.00235.37349.33113.96143.00321.0063.00887.00953.00410.00277.36272.20127.21H&NDauer bis PE/pat in TagenMW235.4371.9541.4186.6207.7308.6

Olivenoeldauerbispedauerbistotdauerpebistot5.0063.000.00319.31422.88103.56254.00410.5071.001041.001138.00468.00314.37314.45127.74

kolonFischoeldauerbispedauerbistotdauerpebistot1.004.001.00371.94482.27110.33288.50391.5062.501507.001727.00933.00311.17344.47152.20CRC


magenFischoeldauerbispedauerbistotdauerpebistot1.0018.001.00207.74389.59181.8581.00278.0089.001851.001852.001062.00307.76381.73234.02Magen


ovarioFischoeldauerbispedauerbistotdauerpebistot3.0059.003.00541.44691.21149.77396.00614.0090.001608.001762.00628.00458.19435.60167.83Ovarial-CA


pankreasFischoeldauerbispedauerbistotdauerpebistot1.0013.000.00186.56273.3086.73119.00225.0046.001322.001322.00595.00199.71218.35105.86Pankreas


time to PE, Time to death, time from PE until to death, total ( days)Total

gruppetypeVariableMinimumMittelwertMedianMaximumStd.abweichungH&NCRCOvarial-CAPankreasMagengesamt

halskopfTotaldauerbispedauerbistotdauerpebistot0.009.000.00266.60376.70110.09170.00387.0067.001041.001138.00468.00290.87287.18125.98Dauer bis PE total /pat in TagenMW266.6394.5625.8200.1195.7336.54

kolonTotaldauerbispedauerbistotdauerpebistot1.004.001.00394.51500.71106.20295.50398.0055.501507.001727.00933.00330.51357.23149.21

magenTotaldauerbispedauerbistotdauerpebistot0.0011.000.00195.70355.48159.7887.00259.0082.001851.001852.001062.00272.15335.34208.02

ovarioTotaldauerbispedauerbistotdauerpebistot3.0059.003.00625.81760.09134.28485.00707.0069.001608.001762.00628.00451.94428.11152.16

pankreasTotaldauerbispedauerbistotdauerpebistot1.0013.000.00200.11292.8892.77127.00219.0049.001322.001322.00801.00220.14248.10123.52

Page: &Z of Pages:&F

Job 1 - Means

The period between start of HPN and death amounts around 3 months, which is too late according to the definition of refractory cachexia

The data indicates that the patients initiated HPN, receive it too late

Average duration until HPN initiation per patient in days

Average period until HPN initiation and until death per patient in each cancer indication


No HPN 300 1,675 228 1,197 447

HPN 43 290 53 209 153

21

2016 2017 2018 2019 2020H&N PancreaticCRC Ovarian Gastric

Average period until death per patient with HPN in days

The average period until initiation of HPN is approximately 337 days, which is similar to the average period from HPN initiation until death (380 days)


Diagramm1

376.7266.6

500.7394.5

760.1625.8

292.9200.1

355.5195.7

Sheet1

376.7500.7760.1292.9355.5

266.6394.5625.8200.1195.7

0 500 1000 1500 2000

Tage von 1st-Therapie bis erste PE (Gesamt)

0

200

400

600

800

1000

Tage

von

ers

ter P

E (G

esam

t) bi

s zu

m V

erst

erbe

n

Effekt der PE auf MortalittKohort: Magen

R-Quadrat= 0.0019

Correlation analysis Overall Survival of Gastric cancer patients, n=153

Effect on cancer survival Gastric

0 500 1000 1500 2000

Tage von 1st-Therapie bis erste PE (Gesamt)

0

500

1000

1500

2000

Tage

bis

zum

Ver

ster

ben

Pat ohne PE

95% CI=(211.71-263.67)SD=279.51Mean=237.69Pat ohne PE:

Effekt auf berleben/MortalittKohort: Magen

R-Quadrat= 0.6159

Days from 1st line cancer Tx to first HPN initiationD

ays

from

1st

HPN

unt

il de

ath

Effect on cancer survival - Gastric

Days from 1st line cancer Tx to first HPN initiation

Day

s un

til d

eath

Patients without PN - - -

R2=0.0019R2=0.6159

Patients without PN

22

Average period until death: 339 days95% CI: 262-417 days

The average survival of Gastric cancer patients after first HPN treatment initiation is approximately 118 days


Patients without PNMean=237.69SD=279,5195% CI=(211.71-263,67)

The largest share of HPN costs of total drug treatment costs is observable in the gastric cancer patient groups

Ovarian cancer has the lowest share of HPN costs

The largest share of cancer drug costs can be seen in Head & Neck and CRC cancer patient groups

23

9282 9694 9304

50273948

1823 945588

1937

2527

H&N CRC Ovarian Pancreatic GastricH&N CRC Ovarian Pancreatic Gastric

16% 9%6%

28%39%

Share of cancer

drug costs

Share of HPN drug

costs

Share of HPN drug costs of total drug costs per patient in (Q0-Q4)

The cost share between cancer & HPN therapies varies between 6% to 39%; in non-GI cancers the cost share of nutrition is lower than of cancer drugs

Study Results Costs

Clinical nutrition use in oncology is currently very low, and patterns of use do not allow to achieve the best possible patient outcomes

Across five cancer types the share of patients who received HPN is on average 16%, with the highest share observed in gastric cancer patients (25%) and the lowest share (12%) amongst patents with Head & Neck cancer

Up to 40% of patients, who were not artificially fed displayed cachexia, which suggests a significant care deficiency in cancer management. Patients who did not receive HPN also showed higher rate of infections and other co-morbidities including decubitus

The study data suggested that patients who did not receive HPN survived on average 70 days less, compared to those who did receive HPN and lived longer, - which highlights the potential benefit of HPN on overall survival

Across five tumor types the share of costs between cancer treatment and home parenteral nutrition varies significantly; with the lowest proportion of costs spent on HPN in comparison with conventional cancer therapy was observed in patients with CRC, ovarian and Head & Neck cancers

24

Summary

Early screening to identify patients at risk of malnutrition, as well as best practices for targeted intervention, including supplemental parenteral nutrition, will be key to improve patients outcomes.

The benefits of appropriate clinical nutrition treatment including overall survival, treatment tolerance and quality of life have to be taken into consideration in patients at risk and/or suffering from malnutrition.

Further research and a clear understanding of the current practices to address benefits of clinical nutrition in oncology is warranted.

Best practices needed to be delineated for early MN diagnosis and clinical nutrition treatment further research is essential

25

Conclusion

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Too little, too late Real World Insights on Current ... · Real World Insights on Current Practice . of Home Parenteral Nutrition in Germany. ESMO 2018, Munich. Prof. Dr. med. Ingolf