Mellar P Davis MD FCCP FAAHPM
Director of Palliative Services
Geisinger Medical Center

Communication and collusion
Early palliative care embedded into palliative
oncology
Outcomes to palliative oncology
Costs and incremental cost effectiveness- whatis the price we are willing to pay

Existential crisis with diagnosis
Focus on anti-cancer therapy
Relative peace of mind on therapy withstabilization of the cancer
Existential crisis with relapse which can berecycled with multiple lines of therapy
Final existential crisis when transition off anticancer therapy

“Unconscious dynamic between patient andclinician which provokes unreflective behavior,
strong emotions and leads to a negative impact
to care”“ Secret agreement”“ Deceitful purpose”“Complicit intent”
Stiefel F 2016

Palliation which is largely centered on tumor
and tumor response and survival rather thanquality of life and patient goals
Minimalize limitations to anti-tumor therapy
and toxicity
Maintain anti-tumor therapies despite its failure
as a means to maintain hope
Individuals are taken off “ active treatment”
when transitioned

Concealment of prognosis- bidirectional
Hope sustained by future developments incancer therapy
The use of non-specific terms- “treatment”
Promises of therapy “when you get better”
despite poor performance related to cancer andits treatment
Failure to address advanced directives andpersonal goals
Application of therapies beyond the known
published benefits

“Watchful waiting” is given little attention“ There is no other choice” but to continue on
therapy
Hope transformed from a verb ( what do you
want to accomplish with the remaining part ofyour life) to a noun ( hope is the nexttreatment)Collusion is fostered by medical activism- doing rather
than being
Patients know that if they take a passive approach todecision-making, the oncologist is likely electaggressive treatment
Accumulated information debt over time
Patients may be relieved with the opportunity toforget what the end result is and / or plan a future
which is incongruent with the course of cancer due toa lack of understanding

de Haes H 2003

The A 2001

722 patients in the CANCor survey withadvanced lung cancer
Only 1/3 recognized that therapy was unlikely tocure their cancerIf they had knew the incurability of their cancer,
they were more likely to avoid aggressive
therapy at the end of life and enter a hospiceprogram earlier
Weeks J 2012
Mack J 2015

Physician may fail to communicate goals oftherapy adequately
Patients may be unable to comprehend the fatal
nature of their cancer

Loss of autonomy- decisions are made without
full disclosure
Missed opportunities at the end of life
Aggressive care at the end of life-repeatedhospitalizations and deaths, ICU admissions anddeaths, repeated emergency department
admissions, no hospice or late hospice referral
Complicated bereavement

Communication training
Early palliative care
Consistent use of symptom and quality of life
tools
Advanced directive discussions
Reshaping discussions away from cancer
centered goals to patient-centered goals
Mindfulness training

Acute care model- crisis intervention in hospitallate in the course of cancer
Oncologist acts as the palliative specialist
where palliative care is missing-rural setting“Congress model” where the oncologist utilizes
multiple specialists by way of consultations-pain
specialist, psychologist, chaplain, social worker
Specialist palliative care integrated into cancer
care as a standard for advanced cancer
Bruera E 2012

Prognosis- “surprise” question“Pathocentric”- at diagnosis of incurability“Oncocentric”- based on the needs and skill setof the oncologist
Sentinel events- pathologic fracture, pleural
effusion, brain metastases“Patient-centered”- based on symptom burden,
performance score, psychosocial factors

Landmark Temel study (NEJM 2010)
demonstrated improved quality of life , lessdepression ( without antidepressants), reduced
aggressive care at the end of life, and an
improved 3 month survival for patients withadvanced lung cancer
Referral was based on diagnosis of incurability
and not symptoms , sentinel events or transitionof careReferral was managed by an interdisciplinary
teamProvide continuity- patient seen regularly
Cooperation and collaboration between
palliative specialist and oncologist
Availability
Embedded outpatient clinics
Delivered on the top of “usual care”
Competent multidisciplinary care and not single
interventions ( education, telephone support ,supportive group therapy)Expert symptom management
Enhanced autonomy through exploring patientunderstanding of the goals of therapy,
prognosis, preferred decision-making andadvanced care planning
Supportive through enhancement of a sense of
self through coping strategies, dignity andmeaning based therapy, spiritual support, family
counselling and education and coordinating
community support

Limited budget within the cancer center
Funding toward drug development and anticancer therapies
Limited number of trained palliative specialists
Many cancer centers value palliative care but
the willingness to fund developments isexpressed in < 20% of centers
Davis M 2015

100 oncology studies
71- clear descriptions of advanced cancer
Primary sites were mostly pancreas and lungcancer
Prolonged survival was clearly the mostimportant outcome
Primary outcome was disease specific survival in
53 / 100 and progression free survival in 45 /100, overall survival 98 / 100

Symptom outcome as the primary outcome- 2 /100
Safety and study specific outcomes- 3 / 100
Patient related outcomes (PROs) weresecondary or tertiary outcomes - 36 / 100
Appropriate PROs instruments - 21 / 100
Term palliative care occurred i- 3 / 100 and notdefined“Best supportive care” frequently used andpoorly describedImpact of adverse events and effects onoutcomes were adequately explained - 22 / 100
Adverse effects were poorly described as“tolerable” from the investigators point of viewor minimized - 53 / 100
Quality of life measures- 31 / 100
Any PRO described - 40 / 100
Harms / benefit and risks discussion - 50 / 100

Response shift
Attrition influences QOL outcomes
Disproportionate optimism
Statistical but not clinically relevant changes
QOL tools with determined meaningful clinically
relevant changes used in a subgroup
Differences in meaningful change withimproved versus diminished QOL
Missing data

Imatinib 2001- beginning of targeted therapy
Tyrosine kinase inhibitors
Hedgehog pathway inhibitors
Antibody targets
Antibody- chemotherapy conjugated agents
Anti-angiogenesis
Histone deacetylase inhibitors
Check point inhibitors

FDA Approval is based on efficacy standards- survival
and toxicity
Costs are based on what the market will bear and noteither incremental value over older approved agents orrecouping costs of drug development
List price is increased each year as much as
10%.Imatinib was 30,000 USD/year 2001 and is 138,000 USD / year 2012
Single producers continue despite the drug being offpatent

Sarpatwari A 2017

Targeted agents are initially used late in thecourse of cancer but cost effectiveness may bebetter with longer durations of disease control
and earlier use
Oncologists are largely unaware of theincremental cost effectiveness ratios per quality
adjusted life year saved (ICER per QALYS) whichleads to choices that significantly increase
family financial toxicity through co-pays (andsociety’s financial toxicity due to distribution ofcosts to all insured) without improving
outcomesVariations across geographic regions
Usual acceptable ICER ranges between 50100,000 USD per QALYSDoes not play a role in approval process in theUS but does in Canada ( Pan-Oncology DrugReview)
Europe registers drugs centrally, reimbursement
may be determined by individual countries
based on clinical and pharmacoeconomicfactors
Hoch J 2013

Gemcitabine vs, gemcitabine plus cisplatin
QALYS is 0.56 for gemcitabine and 0.75 for thecombination
ICER is 33,650 vs. 44,880 USD
Sensitivity analysis : if the ICER ceiling is <60,000 USD then gemcitabine alone is preferredand if 60,000 to 100,000 USD the drug
combination is preferred
Includes progression free survival, survival, preand post chemotherapy health care
Roth J 2012

Irinotecan- ICER QALYS < 50,000 USD
Paclitaxel-ICER QALYS 86,800 USD
Paclitaxel plus ramucirumab- ICER QALYS
1,056,125 USD
Lam J 2016

Total direct health care costs are ½ withpalliation without surgery
QALYS is 0.2 for palliation and 0.48 forresection
ICER is 106,100 EUROS vs. 118,400 EUROS
Ljungman D 2013

Defines mutations which are potential targets
Analysis can be single genes- EGFR, ALK
rearrangements ( FISH, IHC staining, PCA, sequencing)
Sequenome analysis-Next Generation Sequencing,Foundation One Sequencing Platform for multiple
potential targets
Changing face of oncology toward genomic
classifications away from disease site classifications
with exceptions ( not all driver mutations are drivers infound in other cancer sites)
Atherly A 2012

Cost of the test
Cost of the drug targeting the mutation
Frequency of the mutation found in the cancer
population
Effectiveness in disease control and survival
Toxicity and the cost of managing toxicity

A mutation frequency > 5% minimizes the cost factorof the assay
Drug costs then are determined on the ICER per QALYS
Mutation frequency < 5%: ICER per QALYS is acceptable
if the cost of the assay is reduced or the population
which has the mutation is enriched.
Sequenome studies are cost effective if an actionable
mutation is found in > 40% of the population“Negative” appeal to sequenome assays since thisminimizing patient exposures to ineffective therapy.
Exceptions can be PDL-1 assays for which lack ofexpression does not exclude responses altogether
Atherly A 2012

Cost savings to institutions particularly withbundling and value based care
Early palliative ( outpatient ) care
Appointment durations-45-90 minutes
Number of follow-ups – 4-5
Midlevel to Physician FTE- 2 to 1 or 1 to 2
Provider to patient ratio- 1 to 230
Variable telephone follow-up – routine or asneededCost ( direct) per patient enrolled -535 USD
Gaertner J 2015

Extension of life now with lung, colon, prostate,breast, ovarian among other primary sites
New and accumulative toxicities over longer intervals
In the last 12 months of life the average monthly cost is14, 900 Canadian dollars
Unpaid family care-giving costs accounted for 77% of
total palliative costs
The goal to stay at home means someone needs tostay with the patient
Out of pocket expenses threaten the education,
economic stability and well being of the next
generation
Chai H 2014

Communication education
Integration of palliative care early in advanced
cancer as a standard of care and quality
measureService structure and financial support tofacilitate integration
Incorporation of ICER per QALYS into theapproval process and incorporating PROs
Concerted effort to study and minimize family
financial toxicity

Collusion can profoundly damage patients,
impair autonomy and increase the cost of care
Integrated palliative care has both patient andmedical health care benefits
Sequenome assays are more cost effective thanobtaining single gene / mutation assays
depending on populations
Drug value should move from market to ICER
based on QALYSFamily financial toxicity is a rapidly growing
problem