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The American Journal of Managed Care December 2017
Chronic Disease Outcomes From Primary Care Population Health Program Implementation
Jeffrey M. Ashburner, PhD, MPH; Daniel M. Horn, MD; Sandra M. O’Keefe, MPH; Adrian H. Zai, MD, PhD; Yuchiao Chang, PhD; Neil W. Wagle, MD, MBA; and Steven J. Atlas, MD, MPH
Expanding the "Safe Harbor" in High-Deductible Health Plans: Better Coverage and Lower Healthcare Costs
A. Mark Fendrick, MD, and Rashna Soonavala
Impact of Consumer-Directed Health Plans on Low-Value Healthcare
Rachel O. Reid, MD, MS; Brendan Rabideau, BA; and Neeraj Sood, PhD
Insurance Switching and Mismatch Between the Costs and Benefits of New Technologies
David Cutler, PhD; Michael Ciarametaro, MBA; Genia Long, MPP; Noam Kirson, PhD; and Robert Dubois, MD, PhD
ED-Based Care Coordination Reduces Costs for Frequent ED Users
Michelle P. Lin, MD, MPH; Bonnie B. Blanchfield, ScD, CPA; Rose M. Kakoza, MD, MPH; Vineeta Vaidya, MS; Christin Price, MD; Joshua S. Goldner, MD; Michelle Higgins, PA-C; Elisabeth Lessenich, MD, MPH; Karl Laskowski, MD, MBA; & Jeremiah D. Schuur, MD, MHS
Evaluation of the Quality Blue Primary Care Program on Health Outcomes
Qian Shi, PhD, MPH; Thomas J. Yan, MS; Peter Lee, BS; Paul Murphree, MD, MHA; Xiaojing Yuan, MPH; Hui Shao, PhD, MHA; William H. Bestermann, MD; Selina Loupe, BS; Dawn Cantrell, BA; David Carmouche, MD; John Strapp, BA; and Lizheng Shi, PhD, MSPharm
Investigating the Impact of Intervention Refusal on Hospital Readmission
Alexis Coulourides Kogan, PhD; Eileen Koons, MSW, ACSW; and Susan Enguidanos, PhD
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Real-World Economic Value of a 21-Gene Assay in Early-Stage Breast Cancer
Stanley E. Waintraub, MD; Donna McNamara, MD; Deena Mary Atieh Graham, MD; Andrew L. Pecora, MD; John Min, BS; Tommy Wu, BA; Hyun Gi Noh, MSC; Jacqueline Connors, RN, OCN; Ruth Pe Benito, MPH, BS; Kelly Choi, MD; Eric Schultz, BS; & Stuart L. Goldberg, MD
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Real-World Economic Value of a 21-Gene Assay in Early-Stage Breast Cancer

Stanley E. Waintraub, MD; Donna McNamara, MD; Deena Mary Atieh Graham, MD; Andrew L. Pecora, MD; John Min, BS; Tommy Wu, BA; Hyun Gi Noh, MSC; Jacqueline Connors, RN, OCN; Ruth Pe Benito, MPH, BS; Kelly Choi, MD; Eric Schultz, BS; & Stuart L. Goldberg, MD
Universal gene expression profiling of patients with stage II breast cancer resulted in outpatient savings of $11,000 (inclusive of testing costs) within 6 months of initiation of medical therapy.
ABSTRACT

Objectives: Value-based payment reforms shift cost-containment responsibilities to the physician. Although gene expression profiling (GEP) utilizing a 21-gene panel among patients with early-stage, axillary lymph node–negative, hormone receptor–positive, HER2/neu oncogene–negative breast cancer is able to identify a cohort that may achieve excellent outcomes without adjuvant chemotherapy, high up-front costs (list price, $4175) could dissuade usage. 

Study Design: Retrospective review of consecutive patients with breast cancer treated at a single cancer center. 

Methods: Chart review of 227 patients 70 years or younger with outpatient costs (ie, drug average sales price, reagent costs, physician charges) during first 6 months of treatment. 

Results: Of these patients, 68% underwent GEP, with 52%, 43%, and 5% having low, intermediate, and high recurrence risk scores, respectively. Adjuvant chemotherapy was utilized less in genomically profiled cohorts (19% vs 29%; P = .08) and was consistent with recommendations of the recurrence scores. The mean 6-month outpatient costs were $24,955 with adjuvant chemotherapy and $2654 with hormonal therapy. Patients with stage II cancer undergoing GEP received adjuvant chemotherapy at a lower frequency (28.6% vs 86.7%), but patients with stage I cancer who underwent testing were slightly more likely to receive chemotherapy (15.8% vs 14%) because the test identified patients with higher-risk tumors. Universal GEP testing of patients with stage II cancer would have resulted in net savings of $11,494 per patient inclusive of test cost; stage I testing would have increased costs by $4505. Similar trends for grade 2/3 tumors (–$2394) and grade 1 tumors (+$6047) were noted. 

Conclusions: Universal GEP testing of women 70 years or younger with stage II or grade 2/3 lymph node–negative breast cancers would result in lower outpatient costs, inclusive of the diagnostic test, within the first 6-month episode of care. 

Am J Manag Care. 2017;23(12):e416-e420
Takeaway Points

Value-based payment reforms shift cost-containment responsibilities to the physician. Although gene expression profiling utilizing a 21-gene panel among patients with early-stage, axillary lymph node–negative, hormone receptor–positive, HER2/neu oncogene–negative breast cancer is able to identify a cohort that may achieve excellent outcomes without adjuvant chemotherapy, the high up-front cost of profiling could dissuade usage. We retrospectively reviewed consecutive cases of early-stage breast cancer at a community hospital to determine the early economic impact of genomic profiling.
  • Universal testing with the 21-gene breast cancer assay of all patients with stage II or grade 2 breast cancer results in outpatient cost savings within the initial 6 months following treatment initiation (inclusive of test costs) by shifting care away from chemotherapy to oral hormonal treatments. 
  • Testing of patients with stage I or grade 1 breast cancer adds up-front costs but may identify a few patients with unexpected higher-risk tumors, resulting in more intensive therapy and potentially improved late outcomes.
Gene expression profiling (GEP) utilizing a 21-gene panel (Oncotype Dx; Genomic Health, Redwood City, California) in women with early-stage, axillary lymph node–negative, hormone receptor (HR)-positive, HER2/neu oncogene–negative breast cancer is able to identify a cohort in which excellent outcomes can be achieved through the use of hormonal therapy without adjuvant chemotherapy.1-6 The assay evaluates 16 cancer-related genes and 5 reference genes to derive a recurrence score (RS) that estimates the 10-year risk of distant breast cancer recurrence. A recent analysis from the Surveillance, Epidemiology, and End Results (SEER) database on more than 21,000 patients with early-stage breast cancer and low RS, with only 7% receiving adjuvant chemotherapy, found a 5-year breast cancer–specific survival (BCSS) of 99.6%, with continuous RS correlating with BCSS with and without adjustments for age, tumor grade, tumor size, and treatments.5 Future analyses of the TAILORx study, the RxPONDER Trial (SWOG S1007), and the SEER database will hopefully clarify the role of GEP in patients with intermediate and high RS. 

Although GEP in early-stage breast cancer has clinical utility, the cost of the Oncotype Dx assay is not trivial, at a list price of $4175 per study. Cost-effectiveness and budget impact studies, largely based on modeling exercises rather than real-world data, have found that Oncotype Dx testing is likely to improve outcomes, reduce the proportion of patients treated with chemotherapy, and be cost effective with acceptable quality-adjusted life-year (QALY) gains from a payer’s perspective.7-12 For example, among US patients enrolled in a commercial insurance plan, Markov modeling projected a savings of $1160 and a 2- to 3-month QALY gain with GEP testing.13 A recent Pennsylvania Cancer Registry review noted reduced adjuvant chemotherapy use and 1-year health expenditure savings of $15,333 among patients younger than 55 years, but increased use of chemotherapy and higher 1-year costs for patients aged 75 to 84 years.14 As medical payment reform gradually shifts reimbursement from traditional fee-for-service to value-based models, the oncologist will be increasingly required to consider the costs of diagnostic testing. We therefore sought to review the use of GEP at a single center with a focus on outpatient costs incurred during the first 6 months of care. 

METHODS 

Patient Population 

A retrospective chart review was performed at John Theurer Cancer Center (Hackensack, New Jersey) among previously untreated women with invasive breast cancer (stage I or II, axillary lymph node–negative [micrometastasis permitted], HR-positive [estrogen receptor or progesterone receptor], HER2/neu oncogene–negative) who underwent initial evaluations between July 1, 2010, and January 31, 2014. Women older than 70 years were excluded because preliminary analysis from this cancer center demonstrated that age was a significant factor in the decision to receive chemotherapy (23% of patients ≤70 years received chemotherapy vs 6% of patients >70 years; P <.001) or to perform Oncotype Dx genomic profiling (67% of patients ≤70 years underwent the profiling vs 38% of patients >70 years; P = .001). Women younger than 40 years were included in this analysis. Chemotherapy usage rates were higher in this age cohort (18% of patients aged 40-70 years received chemotherapy vs 43% of patients <40 years; P <.05) despite similar testing rates (Oncotype Dx genomic profiling performed in 64% of patients aged 40-70 years and 59% of patients <40 years; P = .71).

Patients were identified using the Cota Inc platform, which extracts and organizes clinical and cost data from electronic health records. All data were de-identified for secondary research analysis. 

Cost Analysis

The analysis started at the time of the initial medical treatment oncology intervention (initiation of chemotherapy or hormonal treatment) and ended 6 months later. Costs of the medications were calculated at the average sales price. J-codes were used to determine administration costs. Office visit evaluation/management codes were reviewed to determine physician fees. Laboratory testing costs were calculated based on practice reagent costs. All costs related to the initial diagnostic evaluation, surgery, and radiation oncology evaluations and treatment were excluded. All costs related to hospitalizations were also excluded. 

Statistical Analysis

Data presentations are descriptive using proportions for categorical variables and means for continuous variables. Chi-squared testing was used to analyze associations. Multivariable analyses entered variables with a P <.1 into the regression models. A 2-sided P <.05 level was considered significant. 

RESULTS

Study Population and Utilization of Oncotype Dx Genomic Profiling

During the study timeframe, 227 patients with early-stage breast cancer met the inclusion criteria, having stage I or II, axillary lymph node–negative (micrometastasis permitted), HR-positive, HER2/neu oncogene–negative breast cancer. Of these, 155 (68%) underwent the Oncotype Dx 21-gene assay. By univariate analysis, grade 2/3 histology (P = .008), the absence of lymph node micrometastasis (P = .07), and treatment by a particular oncologist (P = .009) were each associated with an increased likelihood of undergoing genomic testing. By multivariate analysis, absence of micrometastasis and treatment by a particular oncologist remained significant predictors (both P <.05). Subgroup multivariate analysis of only patients with stage I cancer revealed histologic grade 2/3 and treatment by a particular oncologist to be associated with increased rates of genomic testing, whereas in patients with stage II cancer, absence of micrometastasis, lobular histology, presence of lymphovascular invasion, and treatment by a different particular oncologist were associated with increased testing rates (all P <.05). 

Relationship Between Results of Oncotype Dx Testing and Utilization of Chemotherapy

Among the 155 women with breast cancer who underwent the Oncotype Dx test, 81 (52%) had a low RS, 66 (43%) had intermediate, and 8 (5%) had high. Using the TAILORx scoring system, which is more conservative because it lowers the cutoff for intermediate RS from less than 18 to less than 11, 35 (23%), 99 (64%), and 21 (14%) had a low, intermediate, and high RS, respectively. 

In the entire population of 227 patients, 50 (22%) received adjuvant chemotherapy and 177 (78%) underwent hormonal therapy only. Patients with lower Oncotype Dx RS (traditional or TAILORx, both P <.0001) were less likely to receive adjuvant chemotherapy. For patients with low, intermediate, and high RS, the use of chemotherapy was 4%, 28%, and 100%, respectively (6%, 7%, and 100% with TAILORx). Among the 155 women who underwent Oncotype Dx testing, 29 (19%) received adjuvant chemotherapy. By contrast, of the 72 women who did not undergo GEP, 21 (29%) received chemotherapy (P = .08) (Table 1). Among women with stage I cancer who underwent Oncotype Dx testing, 19 of 120 (16%) received chemotherapy, whereas 8 of 57 (14%) women with stage I cancer who did not undergo testing received chemotherapy (P = .83). Among women with stage II cancer who underwent Oncotype Dx testing, 10 of 35 (29%) received chemotherapy, whereas 13 of 15 (87%) women with stage II cancer without GEP received chemotherapy (P <.001). Univariate analysis and multivariate analysis (all P <.05) revealed primary tumor size less than 2 cm, absence of lymph node micrometastasis, histologic grade 1, absence of lymphovascular invasion, lower Ki-67, and treatment by a different oncologist to be associated with a decreased usage of adjuvant chemotherapy. 

Cost Analysis

Among the 50 patients who received adjuvant chemotherapy, the mean total outpatient cost of care per patient during the first 6 months of treatment was $24,955, compared with $2654 for the 177 patients who received hormonal therapy only (Table 2). The main drivers of costs among patients receiving chemotherapy were hematopoietic growth factors (which were more than double the cost of the chemotherapeutic agents) and supportive care medications (which were on par with the cost of the antineoplastic agents). 

Outpatient costs varied by both cancer stage and performance of GEP. The average outpatient cost for 6 months of therapy for patients with stage I cancer was $20,989 if adjuvant chemotherapy was utilized and $2657 if hormonal therapy was administered. Patients with stage I cancer undergoing GEP received adjuvant chemotherapy at a slightly higher rate (16% of Oncotype Dx–tested patients received chemotherapy vs 14% of patients not genomically profiled). Because more patients with stage I cancer who underwent GEP received chemotherapy, the 6-month outpatient costs increased as a result of testing ($5560 plus $4175 Oncotype cost vs $5230 without testing). If universal GEP testing were applied to patients with stage I cancer, a projected overall net cost increase of $4505 per patient would occur. 

By contrast, universal testing of patients with stage II cancer would result in a net cost savings of $11,494 per profiled patient (including the $4175 test cost). The average outpatient cost of 6 months of therapy for patients with stage II cancer was $29,612 if adjuvant chemotherapy was utilized and $2640 if hormonal therapy was administered. Patients with stage II cancer undergoing GEP received adjuvant chemotherapy at a lower rate (29% of Oncotype Dx–tested patients received chemotherapy vs 87% of patients not genomically profiled). This larger shift away from chemotherapy usage associated with Oncotype Dx profiling led to the observed cost savings (expected average cost if no testing was performed was $26,016 per patient vs $14,522 if universal genomic profiling was performed, inclusive of $4175 Oncotype Dx cost).

Hospitalizations

There were 54 hospitalizations during the 8 months following initiation of treatment in this cohort (who were followed longer since treatment in month 6 may impact outcomes during the next months). Among the 50 women receiving chemotherapy, 27 (54%) were hospitalized a total of 31 times. Among the 177 women receiving hormonal therapy, 16 (9%) were hospitalized a total of 23 times (P <.0001 by patients). The majority of the hospitalizations in the hormonal therapy group were unrelated to treatment, whereas the majority of the hospitalizations in the adjuvant chemotherapy group could be attributed to treatment. 

DISCUSSION

 
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