Applying Genomics to Daily Clinical Practice Current Status and Major Challenges Michael Seiden M.D. Ph.D.

Current Status and Major Challenges The utilization of precision medicine and genomics has not been optimized in the clinical practice Likely >90% of patients with cancer are treated outside of NCI designated cancer center (i.e. community practice) Principle obstacles to address by panelists Fragmentation Knowledge gap Efficient decision support Costs and risks

The US Oncology Network and Vantage Oncology National Reach >350 sites of care in 19 states >1,000 physicians >800K patients treated annually Innovative Clinical Care ~63K patients enrolled in clinical trials Participated in development of nearly 60 FDA-approved cancer therapies Leading Value-Based Care 13 practices accepted to the Oncology Care Model 85% of providers using ClearValue PlusSM 20 disease states in Value Pathways Vantage Oncology The US Oncology Network

The US Oncology Network >45 400 Practices on single EHR Sites of care in 29 states Independent practices >1,300 >250K Option to use McKesson’s co-owned molecular lab Affiliated physicians New cancer patients treated annually 60 Research Sites with 2500 patients enrolled in trials

Network Precision Medicine with NSCLC Pilot Gene Mutations Detected KRAS All mutations in codons 12, 13, and 16 EGFR All common mutations in exons 18-21: p.G719C/S/A, p.T790M, p.L858R, p.L861Q, exon 19 deletions, exon 20 insertions BRAF p.G466V, p.G469A, p.L597V, p.V600E NRAS All mutations in codon 61 PIK3CA (PI3K) p.E542K, p.E545K/Q, p.H1047R MAP2K1 (MEK1) P.Q56P, p.K57N, p.D67N AKT1 p.E17K PTEN p.R233X HER2 Exon 20 insertions Purpose: To test the ability of The US Oncology Network to develop and implement standards for genomic testing Recommendation: Physicians in The Network order the med fusion NSCLC panel for every new Stage 3 and 4 non- squamous NSCLC patient *ALK and ROS1 are tested reflexively

Communicating the Advantages to Practices Improved patient care Greater clinical trial accrual Local marketing opportunities Decreased data entry Payer relationships

Current NSCLC Pilot Status Average of 400 new metastatic NSCLC patients a month across The Network 88 samples tested in April – July, 5.5% of cases

Lessons Learned Test ordering process varies – must customize for each practice Patient financial responsibility is the key concern of the practice Only 50% of time tests ordered by medical oncologist Communication with local pathology departments can be critical Don’t underestimate IT related challenges

Fragmentation

Eligible Population Statistics From April – July, 494 physicians in The US Oncology Network saw at least one new, Stage III / IV NSCLC patient Total of 1,335 patients were seen across The Network from April - July Mean average was 2.7 patients per physician; median was 2 patients # of Physicians

Physician Fragmentation

Lab Fragmentation Lab companies go directly to consumer (community physicians) Avoid electronic connectivity as it slows the sales process Deliver results by PDF which make it difficult to search ordering patterns

Efficient Decision Support and Knowledge Gap

Challenges of Knowledge Gap & Decision Support Average community oncologist sees all blood based and solid tumors. Typically round at two hospitals and have 7-8 hours of office time with 20-25 patients (range 10-40). Recent estimate is 10 minutes to complete EHR documentation. Average 8-10 minutes per patient for review of outside data, history, physical exam, review of recommendations. No simple way to connect to clinical trials in efficient manner. Average age of oncologist in The US Oncology Network is 54. Completed medical oncology training in 1993.

Cost and Risk

Cost Risk High deductible cost plans potentially add burden to patients Risk transfers to clinicians who now need to consider total cost of care

Oncology Care Model A CMMI Pilot Experiment 800 physicians and 35,000 patients to participate in The Network this year Responsible for total costs including labs, medications, imaging, hospitalization, and emergency departments One-sided risk for two years, then two-sided risk If practice profits decrease this will directly impact physician income –a strong motivation to follow well vetted value pathways to maximize predictability Essentially all major commercial payers watching closely and in most cases designing similar alternative payer models

In Conclusion: Challenges for the Panelists What strategies should be developed to achieve a logical, feasible, affordable path forward? Ideally a strategy should: Provide patients with a precision medicine strategy with maximal chance of providing useful information Provide providers with an efficient way to utilize this type of testing and act on these results Provide the greater oncology community with the maximal insight of translating the genomic results with clinical recommendations that have maximal validity Provide payers with confidence that this is money well spent