49
Breast Cancer Clinical Pathway
Committee Development
Meeting
Agenda
Start Time Topic
8:10 am – 8:20 am Welcome, Introductions, and Objectives for the Session
8:20 am – 8:35 am Value-based Care in Breast Cancer Treatment
8:35 am – 8:45 am Welcome, Introductions, and Objectives for the Panelists
8:45 am – 9:00 am Background and Experience of Panelists
9:00 am – 9:15 am Current State of Breast Cancer
9:15 am – 9:55 am Review of Current Treatments for Metastatic Breast Cancer
9:55 am – 10:10 am Break
10:10 am – 10:25 am Q&A Session
10:25 am – 10:50 am Considerations During Pathway Development
10:50 am – 11:20 am Pathway Development for First-line Metastatic Breast Cancer
11:20 am – 11:50 am Pathway Development for Second-line Metastatic Breast Cancer
11:50 am – 12:10 pm Wrapup: Breast Cancer Treatment Pathway and Q&A
Objectives
• Observe the development of a clinical pathway for
breast cancer
• Gain an understanding of the steps involved in
developing a clinical pathway
• Understand the variables factored into clinical pathway
development
• Witness the dialogue and discussion involved in
creating a clinical pathway
Simulation
• The exercise you are about to observe is a simulation of a
pathway development process in breast cancer
• Clinical pathways are intended to streamline physician
prescribing patterns to improve patient outcomes while also
reducing the overall cost of care
• The steering committee for pathway generation involves
clinicians with both breadth and depth of knowledge and
experience with the particular cancer type, in this case,
breast cancer
• This program is typically double-blinded, meaning the
sponsor does not know the panel and the panel does not
know the sponsor to ensure candid and honest feedback
and discussion
Mock Pathway
• The mock pathway simulation was developed to increase
transparency of the clinical pathway development process for
interested stakeholders
• To remove any bias from the mock pathways steering
committee clinical decision making, the programs have
historically been double-blinded in which the steering
committee members are blinded to the interested stakeholder
and the stakeholder is blinded to the specifics of the
participants
• This program is being recorded for the purposes of producing a
final report, after which the recording will be destroyed
• It is the intent of this design to generate candid feedback
regarding your opinions and experience
Value-based Care in Breast Cancer Treatment
Switch from Volume-based to Value-based Care: Improving Patient Health Outcomes while Reducing Cost
Adapted from: American Hospital Association. http://www.hpoe.org/second-curve.shtml. Accessed
August 31, 2017.
Volume-based Value-based
• Value = outcomes/cost
• Payment rewards population
value: quality and efficiency
• Quality impacts reimbursement
• Partnerships with shared risk
• Increased patient severity
• IT utilization essential for
population health management
• Scale increases in importance
• Realigned incentives,
encouraged coordination
• Fee-for-service reimbursement
• High quality not rewarded
• No shared financial risk
• Acute inpatient hospital focus
• IT investment incentives not
seen by hospital
• Standalone care systems can
thrive
• Regulatory actions impede
hospital-physician collaboration
Value-based Care Reimbursement
APM = alternative payment model; MIPS = merit-based incentive payment system; QP = quality
payment.
The Society for Post-Acute and Long-Term Care Medicine. 2015. https://paltc.org/macra.
Accessed August 31, 2017.
Oncology Care Model (OCM)
https://innovation.cms.gov/Files/slides/ocm-overview-slides.pdf
Improve health outcomes and produce higher quality and lower cost of oncology care through improvements in patient-centered
comprehensive care
Comprehensive coordinated cancer care
24/7 access to care
Patient navigation
Improve care coordination
Care management
payment
Enhanced payments
Episode based
Performance based
Quality improvement
driven by data
Application of meaningful and timely
data
OCM Payment Model
• Based on the difference between the expected costs and the actual costs of an individual practice
• Practices must report on quality, communication, coordination, experience, and outcomes
• Must exceed minimum quality threshold to be eligible for payment
Medicare
Fee-for-
Service
Payments
Episode-
based
Payment
Performance-
based
Payment
Total
Payment
• $160 per month per
beneficiary for the
6-month period
beginning with
chemotherapy initiation
• Intended to finance care
transformation
requirements
https://innovation.cms.gov/Files/slides/ocm-overview-slides.pdf
Welcome Panelists
Objectives
• Discuss current treatment guidelines for breast cancer
• Characterize how breast cancer pathways are adopted into
clinical practices
• Identify the critical pieces of information that are used to
develop the pathway and any gaps in information
• Determine the likelihood of pathway implementation
• Discuss the impact of cost on pathway
• Achieve consensus on a metastatic breast cancer systemic
treatment pathway
Agenda
Start Time Topic
8:35 am – 8:45 am Welcome, Introductions, and Objectives for the Panelists
8:45 am – 9:00 am Background and Experience of Panelists
9:00 am – 9:15 am Current State of Breast Cancer
9:15 am – 9:55 am Review of Current Treatments for Metastatic Breast Cancer
9:55 am – 10:10 am Break
10:10 am – 10:25 am Q&A Session
10:25 am – 10:50 am Considerations During Pathway Development
10:50 am – 11:20 am Pathway Development for First-line Metastatic Breast Cancer
11:20 am – 11:50 am Pathway Development for Second-line Metastatic Breast Cancer
11:50 am – 12:10 pm Wrapup: Breast Cancer Treatment Pathway and Q&A
Simulation
• The purpose of this exercise is to simulate a national payer-
sponsored pathway development process in breast cancer
• Based on your experience, you have been selected as a
network member to serve on the steering committee to
create the pathway
• The sponsoring payer’s intent is for this to be a cooperative
pathway development process that takes into account
efficacy, toxicity, cost, and quality
• The audience is interested in not only observing the
academic process of pathway development, but also your
insight regarding barriers and incentives for network
provider pathway adoption
Mock Pathway
• The mock pathway simulation was developed to increase
transparency of the clinical pathway development process
for interested stakeholders
• To remove any bias from the mock pathways steering
committee clinical decision making, the programs have
historically been double-blinded, in which the steering
committee members are blinded to the interested
stakeholder and the stakeholder is blinded to the specifics
of the participants
• This program is being recorded for the purposes of
producing a final report, after which the recording will be
destroyed
• It is the intent of this design to generate candid feedback
regarding your opinions and experience
Introductions
To be in accord with this design, please refrain from using personal or practice
identifiers. Identify with first name, practice region, and practice category.
• What size is your practice?
– Solo practice, small practice (2-5 physicians), medium practice (6-10 physicians),
large practice (>10 physicians)
• In what region is your practice located?
– Northeast, Mid-Atlantic, Southeast, Southwest, Mountain, West
• What best describes your practice?
– Privately held group practice, IPA in partnership with a hospital, fully owned by a
hospital, academic practice
• How many years have you been in practice?
– ≤5, 6-10, 11-15, 16-20, ≥21
• How many unique patients with breast cancer do you actively manage in a
typical week?
• Briefly, what has been your experience in developing
clinical pathways in your practice and/or with payers?
Current State of Breast Cancer
Disease Overview
• 12% of women will be diagnosed with invasive breast cancer
• Only 15% of women with breast cancer have a family history of the disease and only 5%-10% are linked to known familial inherited gene mutations
– BRCA1 mutations are frequently associated with triple-negative breast cancers
• Breast cancer classifications:
http://www.breastcancer.org/symptoms/understand_bc/statistics Accessed Sept. 5, 2017.
http://www.breastcancer.org/symptoms/types/molecular-subtypes Accessed Sept. 5, 2017.
Subtype HR status HER2 status Prognosis
Luminal A HR+ HER2- Good
Luminal B HR+ HER2+ or HER2- Intermediate/Poor
HER2 type HR- HER2+ or HER2- Poor
Basal-like/Triple-negative HR- HER2- Poor
HR = hormone receptor (estrogen-receptor and/or progesterone receptor).
Breast Cancer: Incidence by Subtype
73%
12%
10%
5%
HR+/HER2- HR-/HER2- HR+/HER2+ HR-/HER2+
Kohler BA, et al. J Natl Cancer Inst. 2015;107(6):djv048.
N = 178,125
Treatment of Stage IV Breast Cancer
Systemic
disease or
de novo
stage IV
Bone
disease
present
Bone disease not
present
Add
bone-
modifying
agent
HR+/HER2+
HR+/HER2-
HR-/HER2+
HR-/HER2-
Molecular
profiling
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines ®). Breast Cancer NCCN Evidence
Blocks 2.2017.
https://www.nccn.org/professionals/physician_gls/pdf/breast_blocks.pdf Accessed Sept. 5, 2017.
Breast Cancer: Survival by Subtype
Gong Y, et al. Sci Rep. 2017;7:45411. doi: 10.1038/srep45411.
Part 1: Focus on Triple-negative Breast Cancer (TNBC)
NCCN Guidelines: Adjuvant Therapy for HER2- Disease
Preferred Regimens
Dose Dense AC (doxorubicin/cyclophosphamide)
followed by weekly paclitaxel
Dose Dense AC (doxorubicin/cyclophosphamide)
followed by paclitaxel every 2 weeks
TC (docetaxel and cyclophosphamide)
Other Regimens
Dose Dense AC (doxorubicin/cyclophosphamide)
AC (doxorubicin/cyclophosphamide)
CMF (cyclophosphamide/methotrexate/fluorouracil)
AC followed by docetaxel every 3 weeks
AC followed by weekly paclitaxel
EC (epirubicin/cyclophosphamide)
TAC (docetaxel/doxorubicin/cyclophosphamide)
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines ®). Breast Cancer
NCCN Evidence Blocks 2.2017.
GeparSixto Trial: Addition of Carboplatin to Neoadjuvant Therapy for Early TNBC
• Stage II-III triple-
negative breast
cancer
• Previously untreated
• Non-metastatic
carboplatin
AUC 2 min/mL weekly
+
paclitaxel
80 mg/m2 once per week
non-pegylated liposomal doxorubicin
20 mg/m2 once per week
bevacizumab
15 mg/kg IV every 3 weeks
paclitaxel
80 mg/m2 once per week
non-pegylated liposomal doxorubicin
20 mg/m2 once per week
bevacizumab
15 mg/kg IV every 3 weeks
Von Minckwitz G, et al, Lancet Oncol. 2014;15(7):747-756.
N=291
Randomize
1:1
GeparSixto Trial: Secondary Analysis of BRCA Germline Mutation Cohort
Plus Carboplatin
(n=146)
Noncarboplatin
(n=145)
pCR 57% 41%
BRCA 1/2 mutation cohort
BRCA 1/2 mutation (n=50) 18% 17%
pCR 66% 67%
No BRCA 1/2 mutation cohort
pCR 55% 36%
Hahnen E, et al, JAMA Oncol. 2017 Jul 13. doi: 10.1001/jamaoncol.2017.1007.
[Epub ahead of print]
NCCN Guidelines: Treatment of mTNBC
ER-, PR- and HER2-
(mTNBC) Chemotherapy
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines ®). Breast Cancer
NCCN Evidence Blocks 2.2017.
Recently-approved Breast Cancer Therapies
http://www.fda.gov
Therapy Approval Date
Kisqali (ribociclib) 3/2017
Ibrance (palbociclib) 2/2015
Kadcyla (ado-trastuzumab emtansine) 2/2013
Afinitor (everolimus) 7/2012
Perjeta (pertuzumab injection) 6/2012
(None approved for TNBC)
NCCN Guidelines: Recurrent or Metastatic Breast Cancer for HER2- Disease
Preferred Single Agents
Doxorubicin
Pegylated liposomal doxorubicin
Paclitaxel
Capecitabine
Gemcitabine
Vinorelbine
Eribulin
Other Single Agents
Cyclophosphamide
Carboplatin
Docetaxel
Albumin-bound paclitaxel
Cisplatin
Epirubicin
Ixabepilone
Combinations
CAF/FAC (cyclophosphamide/doxorubicin/fluorouracil)
FEC (fluorouracil/epirubicin/cyclophosphamide)
AC (doxorubicin/cyclophosphamide)
EC (epirubicin/cyclophosphamide)
CMF (cyclophosphamide/methotrexate/fluorouracil)
Docetaxel/capecitabine
GT (gemcitabine/paclitaxel)
Gemcitabine/carboplatin
Paclitaxel/bevacizumab
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines ®). Breast Cancer
NCCN Evidence Blocks 2.2017.
NCCN Evidence Blocks Value Measures
http://www.nccn.org/evidenceblocks. Accessed August 31, 2017.
• Visual representation of “value” based on 5 key measures:
– (E) – Efficacy of Regimen/Agent
o Highly effective to palliative
– (S) – Safety of Regimen/Agent
o No meaningful toxicity to highly toxic
– (Q) – Quality of Evidence
o High-quality evidence to poor-quality/no evidence
– (C) – Consistency of Evidence
o Highly consistent (multiple trials) to anecdotal evidence only
– (A) – Affordability of Regimen/Agent (includes drug cost, supportive
care, infusions, toxicity monitoring, management of toxicity)
o Very inexpensive to very expensive
• Score of 1-5 for each category with 1 being the least favorable and 5
the most favorable, determined by NCCN panel members based on
their knowledge and clinical experience
NCCN Evidence Blocks (Categories & Definitions)
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines ®). Breast Cancer NCCN Evidence
Blocks 2.2017.
.
Efficacy of Regimen/Agent
5 Highly effective: Cure likely and often provides long-term
survival advantage
4 Very effective: Cure unlikely but sometimes provides long-term
survival advantage
3 Moderately effective: Modest impact on survival, but often
provides control of disease
2 Minimally effective: No, or unknown impact on survival, but
sometimes provides control of disease
1 Palliative: Provides symptomatic benefit only
Safety of Regimen/Agent
5 Usually no meaningful toxicity: Uncommon or minimal
toxicities; no interference with activities of daily living (ADLs)
4 Occasionally toxic: Rare significant toxicities or low-grade
toxicities only; little interference with ADLs
3 Mildly toxic: Mild toxicity that interferes with ADLs
2
Moderately toxic: Significant toxicities often occur but life
threatening/fatal toxicity is uncommon; interference with ADLs is
frequent
1 Highly toxic: Significant toxicities or life threatening/fatal toxicity
occurs often; interference with ADLs is usual and severe
Quality of Evidence
5 High quality: Multiple well-designed randomized trials and/or meta-analyses
4 Good quality: One or more well-designed randomized trials
3 Average quality: Low quality randomized trial(s) or well-designed non-
randomized trial(s)
2 Low quality: Case reports or extensive clinical experience
1 Poor quality: Little or no evidence
Consistency of Evidence
5 Highly consistent: Multiple trials with similar outcomes
4 Mainly consistent: Multiple trials with some variability in outcome
3 May be consistent: Few trials or only trials with few patients, whether randomized
or not, with some variability in outcome
2 Inconsistent: Meaningful differences in direction of outcome between quality trials
1 Anecdotal evidence only: Evidence in humans based upon anecdotal experience
Affordability of Regimen/Agent (includes drug cost, supportive care, infusions,
toxicity monitoring, management of toxicity)
5 Very inexpensive
4 Inexpensive
3 Moderately expensive
2 Expensive
1 Very expensive
5
4
3
2
1
E = 4
S = 4
Q = 3
C = 4
A = 3
E S Q C A
Example Evidence Block
5
4
3
2
1
E = Efficacy of Regimen/Agent
S = Safety of Regimen/Agent
Q = Quality of Evidence
C = Consistency of Evidence
A = Affordability of Regimen/Agent
E S Q C A
NCCN Guidelines: Recurrent or Metastatic Breast Cancer for HER2- Disease
A = Affordability of Regimen/Agent; C = Consistency of Evidence; E = Efficacy of Regimen/Agent;
Q = Quality of Evidence, S = Safety of Regimen/Agent.
Preferred Single Agents
Doxorubicin
Pegylated Liposomal
Doxorubicin Paclitaxel Capecitabine
Gemcitabine Vinorelbine Eribulin
5
4
3
2
1
E S Q C A
5
4
3
2
1
E S Q C A
5
4
3
2
1
E S Q C A
5
4
3
2
1
E S Q C A
5
4
3
2
1
E S Q C A
5
4
3
2
1
E S Q C A
5
4
3
2
1
E S Q C A
NCCN Guidelines: Recurrent or Metastatic Breast Cancer for HER2- Disease
Cyclophosphamide Carboplatin Docetaxel
Albumin-bound
paclitaxel
Cisplatin Epirubicin Ixabepilone
Other Single Agents
5
4
3
2
1
E S Q C A
5
4
3
2
1
E S Q C A
5
4
3
2
1
E S Q C A
5
4
3
2
1
E S Q C A
5
4
3
2
1
E S Q C A
5
4
3
2
1
E S Q C A
5
4
3
2
1
E S Q C A
A = Affordability of Regimen/Agent; C = Consistency of Evidence; E = Efficacy of Regimen/Agent;
Q = Quality of Evidence, S = Safety of Regimen/Agent.
NCCN Guidelines: Recurrent or Metastatic Breast Cancer for HER2- Disease
Combinations
5
4
3
2
1
E S Q C A
5
4
3
2
1
E S Q C A
5
4
3
2
1
E S Q C A
5
4
3
2
1
E S Q C A
5
4
3
2
1
E S Q C A
5
4
3
2
1
E S Q C A
5
4
3
2
1
E S Q C A
5
4
3
2
1
E S Q C A
5
4
3
2
1
E S Q C A
Docetaxel/
Capecitabine
GT
(gemcitabine/
paclitaxel)
Gemcitabine/
Carboplatin
Paclitaxel/
Bevacizumab
FEC
(fluorouracil/
epirubicin/
cyclophosphamide)
AC
(doxorubicin/
cyclophosphamide)
EC
(epirubicin/
cyclophosphamide)
CAF/FAC
(cyclophosphamide/
doxorubicin/
fluorouracil)
CMF
(cyclophosphamide/
methotrexate/
fluorouracil)
A = Affordability of Regimen/Agent; C = Consistency of Evidence; E = Efficacy of Regimen/Agent;
Q = Quality of Evidence, S = Safety of Regimen/Agent.
Break
Q&A Session
Welcome Back Panelists
Considerations During Pathway Development
Pathway Development
Collaboration between payer and provider:
• Develop pathway based on currently available
treatments
• Discuss what factors are associated with treatment
preferences and inclusion/exclusion (eg, efficacy, safety,
practice economics, patient burden, MOA, disease
characteristics, etc)
• Facilitate participating physician consensus using the
highest level of evidence
• Intent to define minimum regimens to cover 80% of
eligible patients
Pathway Development (Cont’d)
Collaboration between payer and provider:
• Allow room for individualized medicine and physician
discretion for best clinical practice
• Provide an efficient means of measuring and
communicating compliance
• Identify potential issues with pathway
adoption/compliance overall and with specific therapies
• Provide incentive for compliance, creating a win-win-win
scenario for patients, physicians, and the payer
• All pathways validated by external sources such as
ASCO, NCCN, etc
ASCO = American Society of Clinical Oncology.
The Golden Rules
• Choice of treatment should always be guided by
efficacy if clinically relevant
• If efficacy between therapeutic alternatives is equal,
then toxicity might drive choice
• When efficacy and toxicity are similar among regimens,
economics should drive utilization
General Rules of Pathways
• A clinical trial is always compliant and the preferred
therapy when available
• Palliative care and hospice are reasonable at any time
for the appropriate patient
• It is expected and is good clinical medicine for up to
20% of patients to be treated off pathways
• The treatment provided should be consistent with the
intent of the pathway
Pathway Development for Metastatic Triple-negative Breast Cancer
Pathway Creation First-line mTNBC
• What are the most important parameters that you consider
for patients with mTNBC?
– Overall survival
– PFS
– Response rate
– Time to response
– Duration of response
– Depth of response
– Toxicity
– Symptom relief
– Sites of metastases
– Other
mTNBC = metastatic triple-negative breast cancer; PFS = progression-free survival.
Pathway Creation First-line mTNBC (Cont’d)
• What is the role of sequential single-agent versus
combination chemotherapy?
• What is the impact of adjuvant therapy selection on choice
for metastatic treatment?
• What is the impact of adjuvant therapy response on choice
for metastatic treatment?
mTNBC = metastatic triple-negative breast cancer.
NCCN Guidelines: Recurrent or Metastatic Breast Cancer for HER2- Disease
Preferred Single Agents
Doxorubicin
Pegylated liposomal doxorubicin
Paclitaxel
Capecitabine
Gemcitabine
Vinorelbine
Eribulin
Other Single Agents
Cyclophosphamide
Carboplatin
Docetaxel
Albumin-bound paclitaxel
Cisplatin
Epirubicin
Ixabepilone
Combinations
CAF/FAC (cyclophosphamide/doxorubicin/fluorouracil)
FEC (fluorouracil/epirubicin/cyclophosphamide)
AC (doxorubicin/cyclophosphamide)
EC (epirubicin/cyclophosphamide)
CMF (cyclophosphamide/methotrexate/fluorouracil)
Docetaxel/capecitabine
GT (gemcitabine/paclitaxel)
Gemcitabine/carboplatin
Paclitaxel/bevacizumab
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines ®). Breast Cancer
NCCN Evidence Blocks 2.2017.
Pathway Creation Second-line mTNBC
• What is the impact of response to first-line therapy?
• What is the impact of tolerance to first-line therapy?
• What is the impact of sites of metastases?
• What is the impact of performance status?
• What is the role of sequential single-agent vs combination
chemotherapy?
Wrapup: Breast Cancer
Treatment Pathway
Questions?
