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?