Defining Value in Breast Cancer

Published Online: Sunday, July 17, 2016
A conference workshop sponsored by The Institute for Value-Based Medicine on value in the context of breast cancer.
Speaker:
Kimberly L. Blackwell, MD
Professor of Medicine
Assistant Professor of Radiation Oncology
Duke University Medical Center
Durham, NC

Moderator:
Andrew Pecora, MD
Chief Innovations Officer
Professor and Vice President of Cancer Services
John Theurer Cancer Center at Hackensack
University Medical Center
Regional Cancer Care Associates, LLC
Professor of Medicine and Oncology at Georgetown University
Hackensack, NJ

 


At a national meeting, the second-in-command at the Office of Management and Budget stood up and said, “We are spending too much money on breast cancer.” When pressed for details—what kind of breast cancer, which stages, which types of treatment—the answer was essentially, “Oh, we don’t know. We have no idea. We just know we can’t spend as much as we’re spending.”
 
This lack of clarity was echoed by Kimberly L. Blackwell, MD, who opened the workshop by lamenting the paucity of current data on which to base assessments of value in breast cancer treatment. “It’s almost appalling that we can sequence the human genome but we don’t know exactly how much we’re paying for breast cancer each year in the United States,” Dr Blackwell said. “We need more data, we need more data, we need more data. If we’re going to make an argument that value is important in breast cancer, we’ve got to start with getting the data.”
 
Based on the most recent data available—collected before the introduction of several targeted agents—per-patient costs appear to be more reasonable for stage I versus metastatic breast cancer (MBC).1,2 Whether the introduction of new and more expensive treatments correlates with improved outcomes remains unclear as those data are equally outdated. A study comparing the not-so-recent time periods of 1994 to 1996 and 2004 to 2006 showed concurrent increases in per-patient costs and 5-year survival rates for patients with stage II and III disease.3 “Spending seems to correlate a little bit with outcome, but this is the only data I could find,” Dr Blackwell noted.
 

Small Guideline Change, Wide-Ranging Impact
Next, Dr Blackwell examined the unknown ramifications of SOFT (Suppression of Ovarian Function Trial) and a recent change in the American Society of Clinical Oncology (ASCO) guidelines. SOFT did not meet its primary end point, but the data suggested that ovarian function suppression might benefit young women and those who had received prior chemotherapy.4 Then the new ASCO guidelines came out, stating that premenopausal ER-positive (ER+) stage I or II patients at higher risk of recurrence may be offered ovarian suppression in addition to endocrine therapy.5
 
“I’m a practicing oncologist and this is what I read,” she said. “I don’t really know what higher risk is since they don’t define it, but anyone I deem higher-risk should get ovarian suppression. So if I’m going to shut down a woman’s ovaries, and I’m going to put her on an aromatase inhibitor, then I have to worry about her bones. So this is where the snowball gets a little bigger as we’re going down the hill here. So now you’ve got to bring the patient in once a month for a shot [of a luteinizing hormone-releasing hormone agonist] and twice a year for a shot [of denosumab] because this is what the data would suggest. So we’ve gone from ‘Here’s your pill, I’ll see you at 3, 6, and 9 months’ to now you’ve got to come in to the office once a month.”
 
“So, I thought I would be clever and show some real-life data about how cost-effective preventing breast cancer recurrence and bony fractures is and why we should do it. And here are the articles I found,” Dr Blackwell said, pointing to a blank screen. “They’re right here. There are none.” She estimated that the additional cost for drugs would be close to $200,000 at her own institution, but did not hazard a guess as to the potential economic benefits. “So, I’m hoping what I showed you with this example is how a change in practice guidelines that we take at face value has a tremendous impact on the cost of care. “
 

Value in Early Stage vs Metastatic Breast Cancer
Dr Blackwell also cited the implications of the CLEOPATRA (Clinical Evaluation of Pertuzumab and Trastuzumab) trial, which demonstrated an unprecedented 15.8-month improvement in overall survival when pertuzumab—a humanized monoclonal antibody against HER2—was added to trastuzumab and docetaxel in MBC.6 This is a truly impressive survival advantage, but as a cost-analysis, published in the Journal of Clinical Oncology, demonstrated, it is also very expensive. At an annual estimated incidence of 17,450 eligible patients with metastatic HER2 breast cancer, the authors estimated the incremental cost of adding pentuzumab to be $3.71 billion.7 Although some concerns have been raised with the analysis, it emphasizes a key point: as therapy for MBC becomes more effective, it also becomes very expensive. Treatment of early-stage breast cancer (ESBC) provides greater value. For example, an analysis of the incremental costs of trastuzumab based on 2 National Cancer Institute–sponsored trials demonstrated a cost per quality-adjusted life-year of $26,417, which is well below accepted thresholds of cost-effectiveness.8
 
So while we are spending a lot of money in the early stage setting, it’s cost-efficient treatment because it’s preventing higher expenses associated with recurrence. The key takeaway, according to Dr Blackwell, is that the goal should be to prevent recurrences.
 

The Value of Genomic Predictors
Genomic predictors provide a way to determine a priori the patients most likely to benefit from a given therapy. Dr Blackwell believes that they definitely provide value. Oncotype DX assesses the likelihood of recurrence and benefit of chemotherapy for patients with early-stage, ER+ breast cancer. It has rigorously validated results and is included in the National Comprehensive Cancer Center Network and the ASCO treatment guidelines.9
 
The Breast Cancer Index is a validated biomarker test to predict the likelihood of benefit from extended endocrine therapy for patients with ER+ ESBC. “We now have an assay that is so simple. If you get a high score, then there’s a 16.5% absolute reduction in the chance of breast cancer coming back if you continue endocrine therapy past the standard 5 years. If it’s low, there’s basically no benefit,” said Dr Blackwell, citing a 2010 study published in Lancet Oncology.10 “Assays like this are going to help us refine the value of what we do in an extended way.”
 

Conclusion
Dr Blackwell summed up her presentation with the following observation: “One of the things that we’re all struggling with in day-to-day practice is that we want to follow the guidelines, but the reality is, we don’t know who to follow the guidelines in. The impact on our practice and, more importantly, our patient’s life, as well as the cost, has not been considered in helping us make decisions on how to follow the guidelines.”
 
She emphasized that even the most expensive therapies can be highly cost-effective and provide value to all parties in the early stage setting, while “value” in the incurable or metastatic setting is not clear.
 
 
Discussion and Consensus
In the ensuing discussion, several additional points were raised and the group came to an agreement on the following:
  • Defining value in breast cancer care is complicated by the fact that costs are neither adequately documented nor transparent, nor entirely predictable because of the following:
    • There is a lack of up-to-date pharmacoeconomic data.
    • Cost shifting between departments obscures true costs of care.
    • Suggestive study results and minor guideline changes may have wide-ranging and unforeseen impact on clinical practice and costs.
    • There was discussion regarding the feasibility of routine or mandatory incorporation of value assessments into drug development.
  • Value assessments and recommendations must be subgroup-specific:
    • Costs and other considerations for ESBC and MBC clearly differ.
    • Greater value has been demonstrated for ESBC treatments, which can reduce recurrences and future costs, than for MBC treatments.
  • There is absolute evidence that precision medicine can drive value and should be supported and uniformly paid for:
    • An example was cited from New Jersey, where based on a study demonstrating that use of Oncotype DX for stage I and II patients provided a net benefit to the payer, 2 major insurers modified their polices to require administration of the test before patients receive chemotherapy.
  • A firm stance on what NOT to do may be the most realistic approach to promoting value:
    • Rather than debating whether it’s worth it to extend median life expectancy by X months, it may be more useful to focus on situations where there is no grey area, where there is clear distinction between appropriate and inappropriate use of diagnostics or supportive treatment.
  •  Site of care has a major impact on costs:
    • There is considerable variance between areas of the country, academic centers, 340(b) hospitals, and community practices.
    • The group discussed the impact of the recently announced CMS formula changing Medicare Part B payments to a flat fee. Noting that few community oncologists would take the risk of stocking a $4000 product for a margin of $16.50, they predicted a shift to more hospital-administered therapy, which would drive up the cost of care due to their higher cost basis.
 
References
1. Farina KL. The economics of cancer care in the United States. Evidence-Based Oncology. 2012;18(spec 1):SP38-SP39    
2. Warren JL, Yabroff KR, Meekins A, Topor M, Lamont EB, Brown ML. Evaluation of trends in the cost of initial cancer treatment. J Natl Cancer Inst. 2008;18;100(12):888-897. doi: 10.1093/jnci/djn175.
3. Feinstein AJ, Long J, Soulos PR, et al. Older women with localized breast cancer: costs and survival rates increased across two time periods. Health Aff (Millwood). 2015;34(4):592-600. doi: 10.1377/hlthaff.2014.1119
4. Francis PA, Regan MM, Fleming GF, et al; SOFT Investigators; International Breast Cancer Study Group. Adjuvant ovarian suppression in premenopausal breast cancer. N Engl J Med. 2015;372(5):436-446. doi: 10.1056/NEJMoa1412379.
5. Breast cancer. American Society of Clinical Oncology website. http://www.asco.org/practice-guidelines/quality-guidelines/guidelines/breast-cancer. Accessed 2016.
6. Swain SM, Kim SB, Cortés J, et al. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2013;14(6):461-471. doi: 10.1016/S1470-2045(13)70130-X.
7. Durkee BY, Qian Y, Pollom EL, et al. Cost-effectiveness of pertuzumab in human epidermal growth factor receptor 2-positive metastatic breast cancer. J Clin Oncol. 2016;34(9):902-909. doi: 10.1200/JCO.2015.62.9105.
8. Garrison LP Jr, Lubeck D, Lalla D, Paton V, Dueck A, Perez EA. Cost-effectiveness analysis of trastuzumab in the adjuvant setting for treatment of HER2-positive breast cancer. Cancer. 2007;110(3):489-498.
9. Oncotype DX test. Breastcancer.org website. http://www.breastcancer.org/symptoms/testing/types/oncotype_dx. Accessed 2016.
10. Albain KS, Barlow WE, Shak S, et al; Breast Cancer Intergroup of North America. Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer on chemotherapy: a retrospective analysis of a randomised trial. Lancet Oncol. 2010;11(1):55-65. doi: 10.1016/S1470-2045(09)70314-6. 
 
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