The Lynx Group

Value Frameworks Unreliable in Assessing Novel Hematologic Therapies

February 2017, Vol 8, No 1

San Diego, CA—The American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO) developed frameworks to determine the relative value of novel therapeutic agents. These value frameworks, however, may need to be modified to assess treatments for hematologic malignancies, suggested Matthew C. Cheung, MD, SM, FRCPC, Clinical Hematologist, Odette Cancer Centre, Toronto, Ontario, Canada, at the 2016 American Society of Hematology meeting.

When applied to treatments for blood cancers, the scoring varied dramatically between frameworks.

“Current value frameworks are challenging to apply to therapies for hematologic malignancies,” said Dr Cheung. “When studies could be scored, the correlations between ASCO and ESMO results were poor, suggesting that these frameworks may not reliably identify the value of therapies in hematology. Consideration for the unique outcomes and toxicities in this population is warranted.”

The creation of reliable value frameworks is especially important in hematology, because of the disproportionate costs that are borne by patients with hematologic malignancies, Dr Cheung said.

“ASCO and ESMO value frameworks were developed to determine the relative value associated with new solid tumor therapies, but it is unclear if these frameworks can be applied in the assessment of treatments for blood cancer,” he said.

Disagreements in Scoring

Dr Cheung and colleagues identified all therapies for hematologic malignancies that were approved by the FDA, European Medicines Agency, or Health Canada from 2006 to 2015, and conducted a systematic review of randomized controlled clinical trials for these therapies. The studies were scored by 2 independent reviewers using the ASCO Value Framework version 1 (score range, –20 to 130), the ASCO Value Framework version 2 (lower range undefined to 180), and the ESMO Magnitude of Clinical Benefit Scale (range, 1-5).

The researchers identified and scored 23 randomized controlled clinical trials of hematologic malignancies. Of these, 7 reported primary outcomes unique to hematologic malignancies, including time to disease progression in multiple myeloma, cytogenetic response in chronic myeloid leukemia, and symptomatic response in multicentric Castleman’s disease. Overall survival and progression-free survival were the main outcome measures.

The median ASCO Value Framework version 1 score for the clinical trials was 24. The median ASCO Value Framework version 2 score was 26.7. The median ESMO Magnitude of Clinical Benefit Scale score was 2.

Using the 2-reviewer system to score clinical trials yielded disagreements for each framework.

“The disagreements between the 2 scorers occurred because the 2 individuals had different interpretations on how to apply the ASCO or ESMO frameworks or how to score toxicities,” Dr Cheung explained. “For example, ASCO version 2 requires specific calculation of the number of grade 1 to 2 and grade 3 to 4 toxicities, but doesn’t give guidance on how to score a study that might not present toxicities broken down in this manner.”

“As another example, the ESMO system would downgrade a score if there is an irreversible or severe long-lasting toxicity, but this is quite subjective,” said Dr Cheung.

Poor Correlation Between Scoring Systems

The researchers also measured the concurrent validity between the ASCO and ESMO scores with Spearman’s rank-order correlation. The correlation coefficient between the ASCO Value Framework version 1 and the ESMO Magnitude of Clinical Benefit Scale scores was 0.10 (95% confidence interval [CI], –0.37 to 0.53), suggesting that the correlation was not significantly different from chance. The correlation coefficient between the ASCO Value Framework version 2 and the ESMO scale was –0.21 (95% CI, –0.59 to 0.24). The correlation coefficient between the 2 ASCO Value Framework versions was 0.30 (95% CI, –0.15 to 0.65).

Given these discrepancies, both scoring systems could be improved, Dr Cheung observed.

“Whether it’s for scoring solid tumor or hematologic malignancies, there are quite a few clarifications that are still warranted in defining ways in which quality of life and toxicity could impact the score,” he said.

“As the ASCO and ESMO frameworks continue to evolve, a partnership with hematologic societies and their patients would be fruitful,” concluded Dr Cheung.

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