A multigene prognostic assay for selection of adjuvant chemotherapy in patients with T3, stage II colon cancer: impact on quality-adjusted life expectancy and costs.

OBJECTIVES: Uncertainty exists regarding appropriate and affordable use of adjuvant chemotherapy in stage II colon cancer (T3, proficient DNA mismatch repair). This study aimed to estimate the effectiveness and costs from a US societal perspective of a multigene recurrence score (RS) assay for patients recently diagnosed with stage II colon cancer (T3, proficient DNA mismatch repair) eligible for adjuvant chemotherapy. METHODS: RS was compared with guideline-recommended clinicopathological factors (tumor stage, lymph nodes examined, tumor grade, and lymphovascular invasion) by using a state-transition (Markov) lifetime model. Data were obtained from published literature, a randomized controlled trial (QUick And Simple And Reliable) of adjuvant chemotherapy, and rates of chemotherapy use from the National Cooperative Cancer Network Colon/Rectum Cancer Outcomes study. Life-years, quality-adjusted life expectancy, and lifetime costs were examined. RESULTS: The RS is projected to reduce adjuvant chemotherapy use by 17% compared with current treatment patterns and to increase quality-adjusted life expectancy by an average of 0.035 years. Direct medical costs are expected to decrease by an average of $2971 per patient. The assay was cost saving for all subgroups of patients stratified by clinicopathologic factors. The most influential variables affecting treatment decisions were projected years of life remaining, recurrence score, and patients' disutilities associated with adjuvant chemotherapy. CONCLUSIONS: Use of the multigene RS to assess recurrence risk after surgery in stage II colon cancer (T3, proficient DNA mismatch repair) may reduce the use of adjuvant chemotherapy without decreasing quality-adjusted life expectancy and be cost saving from a societal perspective. These findings need to be validated in additional cohorts, including studies of clinical practice as assay use diffuses into nonacademic settings.

Laboratory-developed test--SynFRAME: an approach for assessing laboratory-developed tests synthesized from prior appraisal frameworks.

Since the late 1990 s, there has been an unprecedented growth in the development of new molecular and proteomic assays for clinical decision making. Despite the thousands of tests available, a standardized, well-defined, and coherent evaluation framework for these molecular assays is still lacking. We aim to summarize the publicly available appraisal criteria and to develop a succinct and accessible set of criteria that can provide a roadmap for the appraisal of gene-based laboratory developed tests (LDTs). We conducted a systematic literature review of the available molecular diagnostic framework in PubMed MD and CINAHL and identified 91 articles on existing appraisal criteria. We provided a summary of the historical appraisal system and developed an analysis of these appraisal systems, LDT-SynFRAME, which details the major criteria for evaluating molecular diagnostics in the clinical setting. Our goal with the LDT-SynFRAME system is to promote a well-informed dialog among all the stakeholders responsible for the development, approval, reimbursement, and use of new molecular classifiers.

Cost-effectiveness of rituximab as maintenance therapy in patients with follicular non-Hodgkin lymphoma after responding to first-line rituximab plus chemotherapy.

A recent phase III trial demonstrated that maintenance rituximab® therapy after response to first-line treatment with rituximab plus chemotherapy (R-chemo) increases progression-free survival (PFS) for follicular non-Hodgkin lymphoma (f-NHL). A cost-effectiveness analysis of R-maintenance versus observation was conducted from a US payer perspective to estimate PFS and overall survival (OS) over a representative patient's lifetime. Primary outcomes were cost per life-year gained (LYG) and cost per quality-adjusted life-year (QALY) gained. Compared with observation, R-maintenance increased mean PFS by 1.50 years, OS by 1.21 years and QALYs gained by 1.11 years. The incremental cost of maintenance therapy was $38,545. The costs per LYG and QALY gained were $31,934 and $34,842, respectively. Within the limitations of modeling long-term outcomes, R-maintenance therapy in patients who received R-chemo for previously untreated f-NHL compared with observation alone after R-chemo for first-line treatment for f-NHL is cost-effective from the US payer perspective.

US insurance program's experience with a multigene assay for early-stage breast cancer.

OBJECTIVE: National guidelines recommend a 21-gene recurrence score (RS) to aid in adjuvant treatment decision in patients with estrogen receptor (ER)-positive, lymph node (LN)-negative early-stage breast cancer (ESBC). This study was performed to assess the economic implication of the assay in community practices from the perspective of a US payer. METHODS: The study analyzed 952 women with ESBC enrolled with Humana (Louisville, KY) who were tested with the 21-gene RS between June 2006 and June 2010. The proportions of women classified by the assay according to RS risk category, use, costs of chemotherapy regimens and supportive care, and costs of adverse events were obtained from Humana. We adopted a validated Markov model to compute the cost implications of RS for a representative patient. The probability of risk of recurrence, the chemotherapy benefit, and the decision impact of RS were derived from published studies. RESULTS: A total of 255 patients within the tested population received adjuvant chemotherapy. Adjuvant chemotherapy was administered to 10% of women at low risk, 36% of women at intermediate risk, and 72% of women at high risk of recurrence. On the basis of a meta-analysis in the reduction of chemotherapy after RS, the model estimated an average test saving of $1160 per patient. The immediate direct savings for chemotherapy drugs, supportive care, and management of adverse events were $1885, $2578, and $472, respectively. Prevention of recurrence through appropriate treatment of patients at high risk resulted in additional savings of $199. CONCLUSION: The adoption of the 21-gene RS led to targeted management of women with ER-positive, LN-negative ESBC and consequently directed savings to the payer.

US Insurance Program's Experience With a Multigene Assay for Early-Stage Breast Cancer.

PURPOSE: National guidelines recommend a 21-gene recurrence score (RS) to aid in adjuvant treatment decision in patients with estrogen receptor (ER) -positive, lymph node (LN) -negative early-stage breast cancer (ESBC). This study was performed to assess the economic implication of the assay in community practices from the perspective of a US payer. METHODS: The study analyzed 952 women with ESBC enrolled with Humana (Louisville, KY) who were tested with the 21-gene RS between June 2006 and June 2010. The proportion of women classified by the assay according to RS risk category, use, and costs of chemotherapy regimens and supportive care, and costs of adverse events were obtained from Humana. We adopted a validated Markov model to compute the cost implications of RS for a representative patient. The probability of risk of recurrence, the chemotherapy benefit, and the decision impact of RS were derived from published studies. RESULTS: Two hundred fifty-five patients within the tested population received adjuvant chemotherapy. Adjuvant chemotherapy was administered to 10% of women at low risk, 36% of women at intermediate risk, and 72% of women at high risk of recurrence. On the basis of a meta-analysis in the reduction of chemotherapy after RS, the model estimated an average test saving of $1,160 per patient. The immediate direct savings for chemotherapy drugs, supportive care, and management of adverse events were $1,885, $2,578, and $472, respectively. Prevention of recurrence through appropriate treatment of patients at high risk resulted in additional savings of $199. CONCLUSION: The adoption of the 21-gene RS led to targeted management of women with ER-positive, LN-negative ESBC and consequently directed savings to the payer.