Dataset Information

Economic evaluation of adjuvant trastuzumab emtansine in patients with HER2-positive early breast cancer and residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment in Canada.

ABSTRACT:

Background

In the katherine trial, adjuvant trastuzumab emtansine [T-DM1, Kadcyla (Genentech, South San Francisco, CA, U.S.A.)], compared with trastuzumab, significantly reduced the risk of recurrence or death by 50% (unstratified hazard ratio: 0.50; 95% confidence interval: 0.39 to 0.64; p < 0.0001) in patients with her2-positive early breast cancer (ebc) and residual invasive disease after neoadjuvant systemic treatment. A cost-utility evaluation, with probabilistic analyses, was conducted to examine the incremental cost per quality-adjusted life-year (qaly) gained associated with T-DM1 relative to trastuzumab, given the higher per-cycle cost of T-DM1.

Methods

A Markov model comprising a number of health states was used to examine clinical and economic outcomes over a lifetime horizon from the Canadian public payer perspective. Patients entered the model in the invasive disease-free survival (idfs) state, where they received either T-DM1 or trastuzumab. Transition probabilities between the health states were derived from the katherine trial, Canadian life tables, and published literature from other relevant clinical trials (emilia, cleopatra, and M77001). Resource use, costs, and utilities were derived from katherine, other clinical trials, published literature, provincial fee schedules, and clinical expert opinion. Sensitivity analyses were conducted for key assumptions and model parameters.

Results

Compared with trastuzumab, adjuvant T-DM1 was associated with a cost savings of $8,300 per patient and a 2.16 incremental qaly gain; thus T-DM1 dominated trastuzumab. Scenario analyses yielded similar results, with T-DM1 dominating trastuzumab or producing highly favourable incremental cost-utility ratios of less than $10,000 per qaly.

Conclusions

Adjuvant T-DM1 monotherapy is a cost-effective strategy compared with trastuzumab alone in the treatment of patients with her2-positive ebc and residual invasive disease after neoadjuvant systemic treatment.

SUBMITTER: Younis T

PROVIDER: S-EPMC7755445 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Publications

Economic evaluation of adjuvant trastuzumab emtansine in patients with HER2-positive early breast cancer and residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment in Canada.

Younis T T Lee A A Coombes M E ME Bouganim N N Becker D D Revil C C Jhuti G S GS

Current oncology (Toronto, Ont.) 20201201 6

<h4>Background</h4>In the katherine trial, adjuvant trastuzumab emtansine [T-DM1, Kadcyla (Genentech, South San Francisco, CA, U.S.A.)], compared with trastuzumab, significantly reduced the risk of recurrence or death by 50% (unstratified hazard ratio: 0.50; 95% confidence interval: 0.39 to 0.64; <i>p</i> < 0.0001) in patients with her2-positive early breast cancer (ebc) and residual invasive disease after neoadjuvant systemic treatment. A cost-utility evaluation, with probabilistic analyses, wa ...[more]

PMID: 33380873

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Project description:Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate incorporating the human epidermal growth factor receptor 2 (HER2)-targeted antitumor properties of trastuzumab with the cytotoxic activity of the microtubule-inhibitory agent DM1. The antibody and the cytotoxic agent are conjugated by means of a stable linker.We randomly assigned patients with HER2-positive advanced breast cancer, who had previously been treated with trastuzumab and a taxane, to T-DM1 or lapatinib plus capecitabine. The primary end points were progression-free survival (as assessed by independent review), overall survival, and safety. Secondary end points included progression-free survival (investigator-assessed), the objective response rate, and the time to symptom progression. Two interim analyses of overall survival were conducted.Among 991 randomly assigned patients, median progression-free survival as assessed by independent review was 9.6 months with T-DM1 versus 6.4 months with lapatinib plus capecitabine (hazard ratio for progression or death from any cause, 0.65; 95% confidence interval [CI], 0.55 to 0.77; P<0.001), and median overall survival at the second interim analysis crossed the stopping boundary for efficacy (30.9 months vs. 25.1 months; hazard ratio for death from any cause, 0.68; 95% CI, 0.55 to 0.85; P<0.001). The objective response rate was higher with T-DM1 (43.6%, vs. 30.8% with lapatinib plus capecitabine; P<0.001); results for all additional secondary end points favored T-DM1. Rates of grade 3 or 4 adverse events were higher with lapatinib plus capecitabine than with T-DM1 (57% vs. 41%). The incidences of thrombocytopenia and increased serum aminotransferase levels were higher with T-DM1, whereas the incidences of diarrhea, nausea, vomiting, and palmar-plantar erythrodysesthesia were higher with lapatinib plus capecitabine.T-DM1 significantly prolonged progression-free and overall survival with less toxicity than lapatinib plus capecitabine in patients with HER2-positive advanced breast cancer previously treated with trastuzumab and a taxane. (Funded by F. Hoffmann-La Roche/Genentech; EMILIA ClinicalTrials.gov number, NCT00829166.).

Project description:BackgroundThe phase III EMILIA and TH3RESA trials demonstrated clinical benefits of trastuzumab emtansine (T-DM1) therapy in patients with previously treated HER2-positive metastatic breast cancer (MBC). Data from these and other trials showed that T-DM1-associated survival benefits were observed across biomarker subgroups tested in these trials. Prespecified, exploratory analyses of the phase III MARIANNE study examined the effects of HER2-related biomarkers on PFS in patients administered T-DM1 in the first-line MBC setting.MethodsIn MARIANNE, patients with previously untreated HER2-positive MBC were randomized (1:1:1) to trastuzumab plus taxane, T-DM1 plus placebo, or T-DM1 plus pertuzumab. Biomarker subgroups included HER2 and HER3 mRNA expression levels (≤median vs. >median), HER2 staining intensity (IHC 3+ vs. 2+ vs. 0/1+), PIK3CA status (mutated vs. non-mutated), PTEN H-score (≤median vs. >median), and PTEN protein expression level (0 vs. 1+ vs. 2+ vs. 3+ vs. 4+). PFS was analyzed descriptively for each subgroup using Kaplan-Meier methodology. Additional exploratory post-hoc analyses evaluated the effects of HER2 heterogeneity. Multivariate analyses were also performed.ResultsMedian PFS was numerically longer for patients with HER2 mRNA levels >median versus ≤median across treatment arms. In general, there were no predictive biomarkers of benefit for either T-DM1 treatment arm; most hazard ratios were close to 1 with wide confidence intervals that included the value 1. Focal HER2 expression (IHC 3+ or IHC 2+) was present in 3.8% of patients and was associated with numerically shorter PFS in the T-DM1-containing treatment arms versus trastuzumab plus taxane. Compared with non-mutated PIK3CA, mutated PIK3CA was associated with numerically shorter median PFS across treatment groups. Post-hoc multivariate analysis showed HER2 mRNA expression and mutated PIK3CA were prognostic for PFS (P ≤ 0.001 for both biomarkers).ConclusionsIn MARIANNE, biomarkers related to the HER2 pathway did not have predictive value for PFS when comparing T-DM1 (with or without pertuzumab) with trastuzumab plus taxane. However, HER2 mRNA level and PIK3CA mutation status showed prognostic value. Evaluation of other potential biomarkers, including immune markers, is ongoing.Trial registrationRegistration number: NCT01120184 . Date of registration: April 28, 2010 (registered prospectively).

Project description:PurposeThis article reviews the mechanism of action of trastuzumab emtansine (T-DM1), existing clinical data relating to its use for human growth factor receptor 2 (HER2)-positive breast cancer, potential pathways of resistance, and ongoing studies evaluating this novel agent.BackgroundThe development of HER2-targeted therapies has dramatically improved clinical outcomes for patients with any stage of HER2-positive breast cancer. Although the positive effect of these treatments cannot be overstated, treatment resistance develops in the vast majority of those diagnosed with stage IV HER2-positive breast cancer. Moreover, HER2-directed therapies are most effective when combined with cytotoxic chemotherapy. The need for chemotherapy leads to significant adverse effects and a clear decrease in quality of life for those dealing with a chronic incurable disease. T-DM1 is a recently developed, novel antibody-drug conjugate in which highly potent maytanisinoid chemotherapy is stably linked to the HER2-targeted monoclonal antibody, trastuzumab.ResultsPreclinical and phase 1-3 clinical data support the significant antitumor activity of T-DM1. Importantly, several randomized studies also now demonstrate its clear superiority in terms of tolerability compared with standard chemotherapy-containing regimens. Its role in the treatment of trastuzumab-resistant metastatic breast cancer has now been established on the basis of the results of two phase 3 randomized studies, EMILIA (An Open-label Study of Trastuzumab Emtansine (T-DM1) vs Capecitabine + Lapatinib in Patients With HER2-positive Locally Advanced or Metastatic Breast Cancer) and TH3RESA (A Study of Trastuzumab Emtansine in Comparison With Treatment of Physician's Choice in Patients With HER2-positive Breast Cancer Who Have Received at Least Two Prior Regimens of HER2-directed Therapy). The most common toxicities seen with T-DM1 are thrombocytopenia and an elevation in liver transaminases. Significant cardiac toxicity has not been demonstrated. Both in vitro cell line-based studies as well as exploratory analyses of archived tumor samples from the clinical trials are seeking to understand potential mechanisms of resistance to T-DM1. Ongoing studies are also evaluating the use of T-DM1 in the first-line metastatic, neoadjuvant, and adjuvant settings, as well as in combination with other targeted therapies.ConclusionT-DM1 represents the first successfully developed antibody drug conjugate for the treatment of HER2-positive advanced breast cancer.

Project description:Background: The DESTINY-Breast03 clinical trial demonstrated that trastuzumab deruxtecan (T-DXd) outperformed trastuzumab emtansine (T-DM1) in progression-free survival (PFS) in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC). Considering the excessive cost of antibody-drug conjugates, the clinical value of T-DXd must be assessed by both its efficacy and cost. We compared the cost-effectiveness of T-DXd and T-DM1 for patients with HER2-positive mBC pretreated with anti-HER2 antibodies and a taxane from the perspectives of the United States (US) and China. Methods: A comprehensive Markov model based on the DESTINY-Breast03 phase III randomized clinical trial was used to compared the cost and effectiveness of T-DXd and T-DM1 for HER2-positive mBC. Data on direct medical cost and utilities were collected from published literatures. The recorded data included the costs, quality-adjusted life-year (QALY), incremental cost-effectiveness ratio (ICER) and incremental net-health benefit (INHB). Sensitivity analysis was conducted to measure the potential uncertainty due to parameter variability. Additional subgroup cost-effectiveness analysis was performed. Results: Treatment of HER2-positive mBC with T-DXd gained 0.73 QALYs compared with T-DM1 strategy. The incremental cost was $59,942 in the US, with an ICER of $ 82,112/QALY and an INHB of 0.33 QALYs, respectively. In China, the incremental cost of T-DXd versus T-DM1 was $222,680, with an ICER of $305,041/QALY and a negative INHB of -5.18 QALYs. At willingness-to-pay (WTP) threshold of $150,000/QALY in the US and $37,653/QALY in China, the probability of T-DXd as the dominant option was 77.5 and 0.1%, respectively. The unit price of T-DXd greatly influenced the results according to one-way sensitivity analysis. To meet the 50% or 90% chance of being cost-effective, the estimated cost of T-DXd would need to be less than $17.24/mg and $12.06/mg in China, respectively. Conclusion: T-DXd is more cost-effective than T-DM1 for patients with HER2-positive mBC in the US, but not in China at current drug prices.

Dataset Information

Economic evaluation of adjuvant trastuzumab emtansine in patients with HER2-positive early breast cancer and residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment in Canada.

Background

Methods

Results

Conclusions

Publications

Economic evaluation of adjuvant trastuzumab emtansine in patients with HER2-positive early breast cancer and residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment in Canada.

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