TheU&lityofOpioidsforBreakthroughCancerPain

JohnZeppetellaMD(Res),FRCGP,FRCPMedicalDirector,StClareHospice

john.zeppetella@stclarehospice.org.uk

JosepPorta–SalesMD,PhD

InsFtutCatalàd’Oncologiajporta@iconcologia.net

J.Zeppetella

•  GrünenthalLtd•  KyowaKirin•  Takeda•  TevaUK•  Wyeth

Disclosures

J.Porta-Sales

•  Ferrer•  KyowaKirin•  GrünenthalLtd•  Takeda

•  “Breakthroughpainisatransientexacerba4onofpainthatoccurseitherspontaneouslyorinrela4ontoaspecificpredictableorunpredictabletriggerdespiterela4velystableandadequatelycontrolledbackgroundpain.”

Definition

Davies et al. 2009

Background pain

Breakthrough pain

Background analgesia (ATC)

Diagnostic Algorithm

Davies et al. 2009

Subtypes

Breakthrough Pain

Spontaneous Pain Incident Pain

Volitional Non-Volitional

Breakthrough Pain Prevalence

Deandrea et al. 2014

Overall prevalence 59%

•  EuropeanSurveyof1000oncologypaFents•  44%incidentpain,41.5%spontaneouspain,14.5%combinaFon.

•  Themediannumberofepisodeswasthreeaday.

•  ThemedianFmetopeakintensitywas10minutes,

•  ThemedianduraFonofuntreatedepisodeswas60minutes

•  893paFentsstatedthatpainstoppedthemdoingsomething,

•  980paFentswerereceivinganopioidtotreattheirpain

BTcP Characteristics

Davies et al. 2009

Time to Peak Intensity

Davies et al. 2013

BTcP Duration

Davies et al. 2013

BTcP Intra-patient Variability

Pérez Cajaraville et al. 2016

Pain intensity Pain duration

Pain relief

Interference with Aspects of Daily Living

Davies et al. 2013

Breakthrough Pain Impact

Healthcare Costs

Activities

Working

Walking

Rx satisfaction

Quality of Life

Sleep

Relationships

Depression

Anxiety

Zeppetella, 2011

•  Common

•  Heterogeneous•  Relatedtobackgroundpain•  Fastonset•  ShortduraFon•  Burdensome

Management Challenges

1.  PaFentswithpainshouldbeassessedforthepresenceofbreakthroughpain

2.  PaFentswithbreakthroughpainshouldhavethispainspecificallyassessed

3.  Themanagementofbreakthroughpainshouldbeindividualized

4.  ConsideraFonshouldbegiventotreatmentoftheunderlyingcauseofthepain

5.  ConsideraFonshouldbegiventoavoidance/treatmentoftheprecipita&ngfactorsofthepain

APM Recommendations

Davies et al. 2009

Decision Making Pain Aetiology

Analgesia

Condition

Co-morbidities

Patient Preference

Clinical Situation

…

6.  ConsideraFonshouldbegiventomodificaFonofthebackgroundanalgesicregimen“aroundtheclockmedica&on”

APM Recommendations

Davies et al. 2009

Background Analgesic Regimen

Op&misingbackgroundanalgesia(increase≈33%)

AresFllATCanalgesicsuseful?

IsfrequentlyusedtherescuemedicaFonwithoutside-effects?

Overdoseandside-effectrisk Hwang et al. 2003/ Mercadante et al. 2004

Pharmacologicaltreatment

Co-analgesics

OpioidsSOOs

RouteofadministraFon

Portenoy et al. 1997 /William & MacLeod. 2008 /Davies et al. 2009/

Zeppetella et al. 2009

PainIntensity

Time

Management Strategies

Multimodal

Approach

Soares & Chan. 2007.

7.   Opioidsarethe“rescuemedicaFon”ofchoiceinthemanagementofbreakthroughpainepisodes

APM Recommendations

Davies et al. 2009

•  “Breakthroughpain(e.g.incidentpain)canbeeffec4velymanagedwithoral,immediate-releaseopioidsorwithbuccalorintranasalfentanylprepara1ons.”

EAPC Guidance

Caraceni et al 2012

• “Insomecasesthebuccalorintranasalfentanylprepara1onsarepreferabletoimmediate-releaseoralopioidsbecauseofmore-rapidonsetofac4onandshorterdura4onofeffect.”

Breakthrough Pain in Cancer Patients

Davies et al. 2013

64%ofallBTcP<60min

64%incidentBTcP<60min

61%spontaneousBTcP<60min

Symptomatic management

Transmucosal Opioids

Mixed Treatment Comparisons

Jansen et al., 2008; Vissers et al. 2010

Mixed Treatment Comparisons

Zeppetella et al., 2014

•  “Addi4onally,thedatapermitaweakrecommenda4onthatimmediate-releaseformula1onsofopioidswithshorthalf-livesshouldbeusedtotreatpreemp1velypredictableepisodesofbreakthroughpaininthe20–30minprecedingtheprovokingmanoeuvre.”

EAPC guidance

Caraceni et al 2012

8.  Thedoseofopioid“rescuemedicaFon”shouldbedeterminedbyindividual&tra&on

APM Recommendations

Davies et al. 2009

STARTINGOPIOIDDOSE

PAINCONTROLLED/NOADVERSEEFFECTS

PAINCONTROLLED/

ADVERSEEFFECTS

PAINNOTCONTROLLED/NOADVERSEEFFECTS

PAINNOTCONTROLLED/

ADVERSEEFFECTS

CONTINUECURRENTDOSE

DECREASEOPIOIDDOSE

INCREASEOPIOIDDOSE

CHANGETREATMENT

9.   Non-pharmacologicalmethodsmaybeusefulinthemanagementofbreakthroughpainepisodes

10.   Non-opioidanalgesicsmaybeusefulinthemanagementofbreakthroughpainepisodes

11.   Interven&onaltechniquesmaybeusefulinthemanagementofbreakthroughpain

12.  PaFentswithbreakthroughpainshouldhavethispainspecificallyre-assessed

APM Recommendations

Davies et al. 2009

Re-assessment after initiation

•  “Toassureanefficaciousandsafe4tra4on,aclosefollowup(every48–72h)

ofpa4entsstar4nganystrongopioids,includingtransmucosalfentanyl

prepara4ons,mustbecarriedoutun4lappropriate4tra4onisreached.”(1)  analgesia(painrelief)–iniFaleffect(≤15’)*andcompleterelieve

(2)  acFviFesofdailyliving(psychosocialfuncFoning)

(3)  adverseeffects–sedaFon,NV…

(4)  aberrantdrugtaking(addicFonrelatedoutcomes).

•  “Op1miza1onofbackgroundanalgesiashouldbeconsideredifthepa4ents

experience≥3BTcPepisodesfor>2consecu1vedays.”

Porta-Sales et al. 2016 / *Boceta et al. 2016

•  OfferoralNR-morphinefirstline

•  TMfentanylwhenothershort-acFngopioidsareunsuitable.

•  DuetonumerousformulaFons,prescribebybrandtoreducethisriskandrestrictlocalformularies.

•  Anindividual’scircumstancesshouldbeconsideredcarefullytobeforeprescribingaTMproduct

Drugs to Review for Optimised Prescribing

Bulletin 132 | April 2016

•  PaFentsreceivingTMfentanylwhoaresuitableforNRmorphine(andhaven’thaditfirstline)couldbeconsideredforaswitch.

•  PaFentsreceivingthemostcostlyTMfentanylproductscouldbeconsideredforaswitchtoalesscostlyIRfentanylproduct.

•  IdenFfypaFentsregularlyusingmorethan2-4dosesofTMfentanylforbreakthroughpain/24hoursforreview.

•  TMfentanylproductsarelicensedonlyforthemanagementofbreakthroughpaininadultpa&entsusingopioidtherapyforchroniccancerpain.

Drugs to Review for Optimised Prescribing

Bulletin 132 | April 2016

•  Breakthroughpainisacommonheterogeneousproblem

•  Aimtoreducetheintensityandfrequencyofepisodes

•  Oralopioidshavenotbeenformallytested

•  ThestrongestevidenceisforuFlityoftransmucosalfentanyl

•  Buccal,sublingualandnasalpreparaFonsareavailable•  NosimplerelaFonshipbetweentheeffecFvedoseoftransmucosalopioidandATCorrescueopioidmedicaFon

•  ClosefollowuppaFentsonopioids

Summary