ASCO Plenary Studies: Assessing the ‘Value’ of New Treatments

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Deborah Schrag, MD, MPH

Deborah Schrag, MD, MPH

At the 2016 ASCO Annual Meeting, studies presented at the Plenary Session gave attendees new treatment strategies to employ back home. But in the emerging push to contain the cost of new cancer treatments, do the four interventions fit within the new “value framework” for oncology? Deborah Schrag, MD, MPH, Chief of the Division of Population Sciences at the Dana-Farber Cancer Institute and Professor of Medicine at Harvard Medical School, Boston, discussed the trials from the perspective of value.1 “The Plenary Session abstracts demonstrate the most significant progress in our field, but many more abstracts are presented at this meeting that reveal small additional benefits at enormous costs,” she said.

In 2015, the average cost for 1 month’s treatment with a [U.S. Food and Drug Administration]–approved infused chemotherapy agent “broke the $12,000 watershed,” Dr. Schrag reported. “And promising drugs and combinations presented at this meeting have pushed far beyond that ceiling, to the $30,000 per month mark.”

Cancer becomes a “financial catastrophe” if the cost of its treatment exceeds the median household income, currently $44,000 in the United States, she declared. “If resources were infinite, we could adopt every innovation, no matter how small the benefit, but because they are constrained, difficult decisions must be made.”

Although oncologists have not yet been asked to allocate treatments for individual patients, society is facing difficult choices. Being entrusted with both their patients’ and the public’s welfare, oncologists play a role in promoting public dialogue on this issue, Dr. Schrag added.

Value Frameworks Launched

ASCO and at least four other oncology organizations have committed to tackling this issue head-on by developing independent value frameworks to help define value. Although each one asks a slightly different question, all of these systems are meant to help determine whether a cancer treatment is “worth it” to a health-care system, given competing priorities on constrained resources.

The ABACUS program at Memorial Sloan Kettering seeks to determine the “just and fair price” for the launch of a new cancer drug. It considers efficacy, costs, toxicity, novelty of the treatment’s mechanism of action, cost of development, and burden of disease.

These oncology value frameworks are not yet a perfect solution, but they represent a provocative beginning to help us start thinking more systematically about how to incorporate value in the setting of ever-increasing cost of cancer treatment.
— Deborah Schrag, MD, MPH

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The Institute for Clinical and Economic Review (ICER) attempts to evaluate the societal value of a treatment. It combines post hoc cost-effectiveness modeling with expert deliberative panels involving patients and physicians. The National Comprehensive Cancer Network® (NCCN) includes an explicit assessment of physicians’ perception of the value of a treatment.

The European Society for Medical Oncology (ESMO) and ASCO have frameworks that seek to determine the clinical “value” or “benefit” in relation to cost. ESMO uses a “magnitude of clinical benefit scale,” a complex algorithm for estimating benefit, and it aims to inform deliberations about technology adoption and system-wide coverage policies. The ASCO value framework uses a scoring algorithm that considers clinical benefit, toxicity, durability of response, palliation benefit, quality of life, and accomplishment of treatment-free intervals, assigning total points to constitute a net health benefit.

Plenary Session Interventions

From the highest value to the lowest, Dr. Schrag calculated how the findings reported at the Plenary Session fit into the “value framework” according to these various models.

The ANBL0532 trial from the Children’s Oncology Group found that for children with high-risk neuroblastoma, tandem autologous stem cell transplant improved event-free survival at 3 years: 61.4% vs 48.4% with a single autologous stem cell transplant (P = .0081), without additional toxicity.2 [For a more complete discussion of the ANBL0532 trial, see the June 25, 2016, issue of The ASCO Post.]

“For adding tandem autologous stem cell transplant for curative intent in the treatment of toddlers with neuroblastoma, the ASCO score is very high (76 on a scale of 0–130), the ESMO grade is “A,” and the ICER per quality-adjusted life-year (QALY) is less than $50,000,” the threshold generally accepted as cost-effective, noted Dr. Schrag.

“The value of tandem transplant is likely to be exceedingly high from the perspective of individual parents, and the health system value is also likely to be very high,” Dr. Schrag concluded. “All high-income countries will, and should, adopt this. Middle-income countries will seek to adopt it, although access to care and obtaining specialty care may be challenging.”

The phase III CASTOR trial of patients with relapsed/refractory multiple myeloma found that the addition of daratumumab (Darzalex) to bortezomib (Velcade)/dexamethasone significantly improved multiple outcomes in patients with one or more prior lines of therapy.3 Risk of disease progression was reduced by 61% (P < .0001). [For a more complete discussion of the CASTOR trial, see the June 10, 2016, issue of The ASCO Post.]

“Daratumumab produced a major progression-free survival benefit, which will almost certainly translate into an overall survival benefit,” said Dr. Schrag. “However, this will come at a very high cost, more than $10,000 a month. This will result in financial strain for individuals who lack adequate health insurance coverage; therefore, from a health system value perspective, this has a moderate-to-high rating.”

“High-income countries will adopt this or seek to negotiate steep discounts, whereas many middle-income countries will find this promising intervention to be cost-prohibitive,” she predicted.

The combination of short-course radiotherapy and temozolomide followed by maintenance with temozolomide significantly improved survival compared with short-course radiotherapy alone in newly diagnosed elderly patients with glioblastoma, according to the findings of a global cooperative group trial.4 [For a more complete discussion of this trial, see the June 10, 2016, issue of The ASCO Post.] The combination extended overall survival to 9.3 months, compared with 7.5 months with radiotherapy alone, representing a significant 33% improvement (P < .0001); it also prolonged median progression-free survival by 50% (P < .0001).

“Temozolomide is generic and available, and physicians have used it for quite some time. From a health system value perspective, temozolomide plus short-course radiotherapy is viewed as moderate. Its value is low in the absence of a specific mutation,” explained Dr. Schrag. “Most high-income countries will continue to cover it and adopt this strategy if they haven’t already, but adoption will vary greatly in middle-income countries, and some will find it cost-prohibitive.”

Emergence of Value Frameworks

  • Specialty societies are developing value frameworks that will help determine the true value of a given treatment in the context of the health-care system.
  • The current models were applied to the four studies presented at the
    2016 ASCO Plenary Session.
  • Dr. Schrag determined that the least value could be applied to extended letrozole therapy in postmenopausal early breast cancer patients and the highest value, to tandem transplant in high-risk neuroblastoma.
  • Moderate-to-high value was awarded to daratumumab in relapsed/refractory multiple myeloma, whereas moderate value was assigned to temozolomide plus short-course radiotherapy in elderly patients with glioblastoma.

The MA.17R trial evaluated an additional 5 years of letrozole in women with postmenopausal hormone receptor–positive early breast cancer who had tolerated 5 years of aromatase inhibitor therapy after tamoxifen.5 Extended use of letrozole improved disease-free survival by 34% and reduced the risk of contralateral breast cancer by 58% (P = .01). [For a more complete discussion of the MA.17R trial, see the June 10, 2016, issue of The ASCO Post.]

“The first point for this study is that women facing this decision are informed: They have already been on 5 years of an aromatase inhibitor, and so they can make good decisions that are consistent with their experience,” Dr. Schrag commented.

“Thus, the individual value of this strategy will be highly variable, and this will be a preference-driven decision based on risk and treatment tolerance,” she maintained. “There is an excess risk of osteoporosis and fracture and excess cost related to treating that complication; therefore, from a health system value perspective, this intervention was rated low in each of the value frameworks.”

‘A Provocative Beginning’

“These oncology value frameworks are not yet a perfect solution, but they represent a provocative beginning to help us start thinking more systematically about how to incorporate value in the setting of ever-increasing cost of cancer treatment,” Dr. Schrag concluded. The frameworks are not yet practical for clinical decision-making, but software tools in development may help, she added.

“That said, we cannot ignore value deliberations, even though they are often noxious,” closed Dr. Schrag. “Unaffordability of cancer treatment has adverse consequences on patients, physicians, and society as a whole…. It is critical to develop better policies to align care value with our core values.” ■

Disclosure: Dr. Schrag is a consultant for New Century Health.


1. Schrag D: 2016 ASCO Annual Meeting. Plenary Lecture. Presented June 5, 2016.

2. Park JR, Kreissman SG, London WB, et al: 2016 ASCO Annual Meeting. Abstract LBA3. Presented June 5, 2016.

3. Palumbo A, Chanan-Khan AAA, Weisel K, et al: 2016 ASCO Annual Meeting. Abstract LBA4. Presented June 5, 2016.

4. Perry JR, Laperriere N, O’Callaghan CJ, et al: 2016 ASCO Annual Meeting. Abstract LBA2. Presented June 5, 2016.

5. Goss PE, Ingle JN, Pritchard KI, et al: 2016 ASCO Annual Meeting. Abstract LBA1. Presented June 5, 2016.