Breast Cancer Clinical Pathway Committee Development Meeting

Agenda Start Time Topic 8:0 am 8:0 am Welcome, Introductions, and Objectives for the Session 8:0 am 8: am Value-based Care in Breast Cancer Treatment 8: am 8: am Welcome, Introductions, and Objectives for the Panelists 8: am 9:00 am Background and Experience of Panelists 9:00 am 9: am Current State of Breast Cancer 9: am 9: am Review of Current Treatments for Metastatic Breast Cancer 9: am 0:0 am Break 0:0 am 0: am Q&A Session 0: am 0:0 am Considerations During Pathway Development 0:0 am :0 am Pathway Development for First-line Metastatic Breast Cancer :0 am :0 am Pathway Development for Second-line Metastatic Breast Cancer :0 am :0 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 Volume-based Value-based 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 = 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 Adapted from: American Hospital Association. http://www.hpoe.org/second-curve.shtml. Accessed August, 07.

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. 0. https://paltc.org/macra. Accessed August, 07.

Oncology Care Model (OCM) Improve health outcomes and produce higher quality and lower cost of oncology care through improvements in patient-centered comprehensive care Comprehensive coordinated cancer care Enhanced payments Quality improvement driven by data /7 access to care Patient navigation Improve care coordination Care management payment Episode based Performance based Application of meaningful and timely data https://innovation.cms.gov/files/slides/ocm-overview-slides.pdf

OCM Payment Model Medicare Fee-for- Service Payments Episodebased Payment Performancebased Payment Total Payment $60 per month per beneficiary for the 6-month period beginning with chemotherapy initiation Intended to finance care transformation requirements 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 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: am 8: am Welcome, Introductions, and Objectives for the Panelists 8: am 9:00 am Background and Experience of Panelists 9:00 am 9: am Current State of Breast Cancer 9: am 9: am Review of Current Treatments for Metastatic Breast Cancer 9: am 0:0 am Break 0:0 am 0: am Q&A Session 0: am 0:0 am Considerations During Pathway Development 0:0 am :0 am Pathway Development for First-line Metastatic Breast Cancer :0 am :0 am Pathway Development for Second-line Metastatic Breast Cancer :0 am :0 pm Wrapup: Breast Cancer Treatment Pathway and Q&A

Simulation The purpose of this exercise is to simulate a national payersponsored 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 (- physicians), medium practice (6-0 physicians), large practice (>0 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?, 6-0, -, 6-0, 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 % of women will be diagnosed with invasive breast cancer Only % of women with breast cancer have a family history of the disease and only %-0% are linked to known familial inherited gene mutations BRCA mutations are frequently associated with triple-negative breast cancers Breast cancer classifications: Subtype HR status HER status Prognosis Luminal A HR+ HER- Good Luminal B HR+ HER+ or HER- Intermediate/Poor HER type HR- HER+ or HER- Poor Basal-like/Triple-negative HR- HER- Poor HR = hormone receptor (estrogen-receptor and/or progesterone receptor). http://www.breastcancer.org/symptoms/understand_bc/statistics Accessed Sept., 07. http://www.breastcancer.org/symptoms/types/molecular-subtypes Accessed Sept., 07.

Breast Cancer: Incidence by Subtype 0% % % 7% HR+/HER- HR-/HER- HR+/HER+ HR-/HER+ Kohler BA, et al. J Natl Cancer Inst. 0;07(6):djv08. N = 78,

Treatment of Stage IV Breast Cancer HR+/HER+ Systemic disease or de novo stage IV Bone disease present Add bonemodifying agent Bone disease not present Molecular profiling HR+/HER- HR-/HER+ HR-/HER- NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines ). Breast Cancer NCCN Evidence Blocks.07. https://www.nccn.org/professionals/physician_gls/pdf/breast_blocks.pdf Accessed Sept., 07.

Breast Cancer: Survival by Subtype Gong Y, et al. Sci Rep. 07;7:. doi: 0.08/srep.

Part : Focus on Triple-negative Breast Cancer (TNBC)

NCCN Guidelines: Adjuvant Therapy for HER- Disease Preferred Regimens Dose Dense AC (doxorubicin/cyclophosphamide) followed by weekly paclitaxel Dose Dense AC (doxorubicin/cyclophosphamide) followed by paclitaxel every weeks TC (docetaxel and cyclophosphamide) Other Regimens Dose Dense AC (doxorubicin/cyclophosphamide) AC (doxorubicin/cyclophosphamide) CMF (cyclophosphamide/methotrexate/fluorouracil) AC followed by docetaxel every 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.07.

GeparSixto Trial: Addition of Carboplatin to Neoadjuvant Therapy for Early TNBC Stage II-III triplenegative breast cancer Previously untreated Non-metastatic N=9 Randomize : carboplatin AUC min/ml weekly + paclitaxel 80 mg/m once per week non-pegylated liposomal doxorubicin 0 mg/m once per week bevacizumab mg/kg IV every weeks paclitaxel 80 mg/m once per week non-pegylated liposomal doxorubicin 0 mg/m once per week bevacizumab mg/kg IV every weeks Von Minckwitz G, et al, Lancet Oncol. 0;(7):77-76.

GeparSixto Trial: Secondary Analysis of BRCA Germline Mutation Cohort Plus Carboplatin (n=6) Noncarboplatin (n=) pcr 7% % BRCA / mutation cohort BRCA / mutation (n=0) 8% 7% pcr 66% 67% No BRCA / mutation cohort pcr % 6% Hahnen E, et al, JAMA Oncol. 07 Jul. doi: 0.00/jamaoncol.07.007. [Epub ahead of print]

NCCN Guidelines: Treatment of mtnbc ER-, PR- and HER- (mtnbc) Chemotherapy NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines ). Breast Cancer NCCN Evidence Blocks.07.

Recently-approved Breast Cancer Therapies Therapy Approval Date Kisqali (ribociclib) /07 Ibrance (palbociclib) /0 Kadcyla (ado-trastuzumab emtansine) /0 Afinitor (everolimus) 7/0 Perjeta (pertuzumab injection) 6/0 (None approved for TNBC) http://www.fda.gov

NCCN Guidelines: Recurrent or Metastatic Breast Cancer for HER- 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.07.

NCCN Evidence Blocks Value Measures Visual representation of value based on 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 - for each category with being the least favorable and the most favorable, determined by NCCN panel members based on their knowledge and clinical experience http://www.nccn.org/evidenceblocks. Accessed August, 07.

NCCN Evidence Blocks (Categories & Definitions) Efficacy of Regimen/Agent Highly effective: Cure likely and often provides long-term survival advantage Very effective: Cure unlikely but sometimes provides long-term survival advantage Moderately effective: Modest impact on survival, but often provides control of disease Minimally effective: No, or unknown impact on survival, but sometimes provides control of disease Palliative: Provides symptomatic benefit only Safety of Regimen/Agent Usually no meaningful toxicity: Uncommon or minimal toxicities; no interference with activities of daily living (ADLs) Occasionally toxic: Rare significant toxicities or low-grade toxicities only; little interference with ADLs Mildly toxic: Mild toxicity that interferes with ADLs E = Efficacy of Regimen/Agent S = Safety of Regimen/Agent Q = Quality of Evidence C = Consistency of Evidence A = Affordability of Regimen/Agent Moderately toxic: Significant toxicities often occur but life threatening/fatal toxicity is uncommon; interference with ADLs is frequent Highly toxic: Significant toxicities or life threatening/fatal toxicity occurs often; interference with ADLs is usual and severe Quality of Evidence High quality: Multiple well-designed randomized trials and/or meta-analyses Good quality: One or more well-designed randomized trials Average quality: Low quality randomized trial(s) or well-designed nonrandomized trial(s) Low quality: Case reports or extensive clinical experience Poor quality: Little or no evidence Consistency of Evidence Highly consistent: Multiple trials with similar outcomes Mainly consistent: Multiple trials with some variability in outcome May be consistent: Few trials or only trials with few patients, whether randomized or not, with some variability in outcome Inconsistent: Meaningful differences in direction of outcome between quality trials 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) Very inexpensive Inexpensive Moderately expensive Expensive Very expensive Example Evidence Block E = S = Q = C = A =. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines ). Breast Cancer NCCN Evidence Blocks.07.

NCCN Guidelines: Recurrent or Metastatic Breast Cancer for HER- Disease Preferred Single Agents Doxorubicin Pegylated Liposomal Doxorubicin Paclitaxel Capecitabine Gemcitabine Vinorelbine Eribulin 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 HER- Disease Cyclophosphamide Carboplatin Docetaxel Other Single Agents Cisplatin Epirubicin Ixabepilone A = Affordability of Regimen/Agent; C = Consistency of Evidence; E = Efficacy of Regimen/Agent; Q = Quality of Evidence, S = Safety of Regimen/Agent. Albumin-bound paclitaxel

NCCN Guidelines: Recurrent or Metastatic Breast Cancer for HER- Disease CAF/FAC (cyclophosphamide/ doxorubicin/ fluorouracil) Docetaxel/ Capecitabine FEC (fluorouracil/ epirubicin/ cyclophosphamide) Combinations AC (doxorubicin/ cyclophosphamide) GT (gemcitabine/ paclitaxel) EC (epirubicin/ cyclophosphamide) Gemcitabine/ Carboplatin A = Affordability of Regimen/Agent; C = Consistency of Evidence; E = Efficacy of Regimen/Agent; Q = Quality of Evidence, S = Safety of Regimen/Agent. CMF (cyclophosphamide/ methotrexate/ fluorouracil) Paclitaxel/ Bevacizumab

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 0% 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.

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?