Dataset Information

Efficacy and safety of CT-P6 versus reference trastuzumab in HER2-positive early breast cancer: updated results of a randomised phase 3 trial.

ABSTRACT: PURPOSE:Neoadjuvant CT-P6, a trastuzumab biosimilar, demonstrated equivalent efficacy to reference trastuzumab in a phase 3 trial of HER2-positive early-stage breast cancer (EBC) (NCT02162667). We report post hoc analyses evaluating pathological complete response (pCR) and breast pCR alongside additional efficacy and safety measures. METHODS:Following neoadjuvant treatment and surgery, patients received adjuvant CT-P6 or trastuzumab (6 mg/kg) every 3 weeks for???1 year. RESULTS:In total, 271 and 278 patients received CT-P6 and trastuzumab, respectively. pCR and breast pCR rates were comparable between treatment groups regardless of age, region, or clinical stage. Overall, 47.6% (CT-P6) and 52.2% (trastuzumab) of patients experienced study drug-related treatment-emergent adverse events (TEAEs), including 17 patients reporting heart failure (CT-P6: 10; trastuzumab: 7). Two CT-P6 and three trastuzumab patients discontinued adjuvant treatment due to TEAEs. CONCLUSION:Adjuvant CT-P6 demonstrated comparable efficacy and safety to trastuzumab at 1 year in patients with HER2-positive EBC, supporting CT-P6 and trastuzumab comparability.

SUBMITTER: Esteva FJ

PROVIDER: S-EPMC6768896 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Efficacy and safety of CT-P6 versus reference trastuzumab in HER2-positive early breast cancer: updated results of a randomised phase 3 trial.

Esteva F J FJ Baranau Y V YV Baryash V V Manikhas A A Moiseyenko V V Dzagnidze G G Zhavrid E E Boliukh D D Stroyakovskiy D D Pikiel J J Eniu A E AE Li R K RK Rusyn A V AV Tiangco B B Lee S J SJ Lee S Young SY Yu S Y SY Stebbing J J

Cancer chemotherapy and pharmacology 20190819 4

<h4>Purpose</h4>Neoadjuvant CT-P6, a trastuzumab biosimilar, demonstrated equivalent efficacy to reference trastuzumab in a phase 3 trial of HER2-positive early-stage breast cancer (EBC) (NCT02162667). We report post hoc analyses evaluating pathological complete response (pCR) and breast pCR alongside additional efficacy and safety measures.<h4>Methods</h4>Following neoadjuvant treatment and surgery, patients received adjuvant CT-P6 or trastuzumab (6 mg/kg) every 3 weeks for ≤ 1 year.<h4>Results ...[more]

PMID: 31428820

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Project description:BackgroundThe trastuzumab biosimilar CT-P6 has demonstrated equivalent efficacy and comparable safety to reference trastuzumab (RTZ) in clinical trials of human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (EBC). Here, we present the first real-world comparison of CT-P6 versus RTZ with dual HER2-targeted therapy for the neoadjuvant and palliative first-line treatment with HER2-positive EBC and metastatic breast cancer (MBC) patients in two tertiary hospitals in Korea.MethodsWe retrospectively investigated medical records in the Severance Breast Cancer Registry in Korea. We identified patients with HER2-positive EBC (n=254) who had received neoadjuvant chemotherapy with RTZ or CT-P6, plus pertuzumab, carboplatin and docetaxel (TCHP) and untreated stage IV MBC (n=103) who had received palliative first-line treatment with RTZ or CT-P6, plus pertuzumab and docetaxel (THP) between May 2014 and December 2019. The primary endpoints were pathologic complete response (pCR) in the EBC and progression-free survival (PFS) in the MBC cohort. Overall survival (OS), overall response rate (ORR), disease control rate (DCR), and cardiac safety were secondary endpoints.ResultsA similar percentage of EBC patients achieved a pCR with CT-P6 versus RTZ (74.4% [93/125]) vs 69.8% [90/129], p=0.411). For patients with MBC, median follow-up duration was 23.0 and 41.0 months for CT-P6 and RTZ groups, respectively; median PFS did not differ significantly between two groups (13.0 vs 18.0 months, 95% confidence intervals (CIs) 0.0-26.6 vs 11.3-24.7, p=0.976). The ORR, DCR, and cardiac safety profiles did not also show significant difference efficacy outcomes between two groups.ConclusionsThese real-world data suggest that biosimilar trastuzumab CT-P6 has similar effectiveness and cardiac safety to RTZ in HER2-positive EBC and MBC patients, when administered as part of dual HER2-targeted therapy with pertuzumab plus chemotherapy in the neoadjuvant or palliative setting.

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.

Project description:BACKGROUND:This randomised, double-blind study compared PF-05280014 (a trastuzumab biosimilar) with reference trastuzumab (Herceptin®) sourced from the European Union (trastuzumab-EU), when each was given with paclitaxel as first-line treatment for HER2-positive metastatic breast cancer. METHODS:Between 4 April 2014 and 22 January 2016, 707 participants were randomised 1:1 to receive intravenous PF-05280014 plus paclitaxel (PF-05280014 group; n = 352) or trastuzumab-EU plus paclitaxel (trastuzumab-EU group; n = 355). PF-05280014 or trastuzumab-EU was administered weekly (first dose 4 mg/kg, subsequent doses 2 mg/kg), with the option to change to a 3-weekly regimen (6 mg/kg) from Week 33. Treatment with PF-05280014 or trastuzumab-EU could continue until disease progression. Paclitaxel (starting dose 80 mg/m2) was administered on Days 1, 8 and 15 of 28-day cycles for at least six cycles or until maximal benefit of response. The primary endpoint was objective response rate (ORR), evaluating responses achieved by Week 25 and confirmed by Week 33, based on blinded central radiology review. RESULTS:The risk ratio for ORR was 0.940 (95% CI: 0.842-1.049). The 95% CI fell within the pre-specified equivalence margin of 0.80-1.25. ORR was 62.5% (95% CI: 57.2-67.6%) in the PF-05280014 group and 66.5% (95% CI: 61.3-71.4%) in the trastuzumab-EU group. As of data cut-off on 11 January 2017 (using data up to 378 days post-randomisation), there were no notable differences between groups in progression-free survival (median: 12.16 months in the PF-05280014 group vs. 12.06 months in the trastuzumab-EU group; 1-year rate: 54% vs. 51%) or overall survival (median: not reached in either group; 1-year rate: 89.31% vs. 87.36%). Safety outcomes and immunogenicity were similar between the treatment groups. CONCLUSION:When given as first-line treatment for HER2-positive metastatic breast cancer, PF-05280014 plus paclitaxel demonstrated equivalence to trastuzumab-EU plus paclitaxel in terms of ORR. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov, NCT01989676.

Project description:PURPOSE:PF-05280014 is a biosimilar to trastuzumab (Herceptin®). Following demonstration of pharmacokinetic (PK) similarity in healthy volunteers, a comparative clinical study in patients with HER2-positive metastatic breast cancer (mBC) compared the efficacy, safety and immunogenicity of PF-05280014 and trastuzumab sourced from the EU (trastuzumab-EU), both with paclitaxel. METHODS:Population PK of PF-05280014 and trastuzumab-EU was evaluated. RESULTS:Overall, 702 patients were treated: PF-05280014 (n?=?349) and trastuzumab-EU (n?=?353). Peak-and-trough serum drug concentration samples were collected (selected doses) following repeated intravenous administration of PF-05280014 or trastuzumab-EU. Population PK analysis was performed with drug concentration-time data to cycle 17 for each compound, using nonlinear mixed effect modeling. Potential baseline covariates (circulating HER2 concentrations, body weight, Japanese race, Eastern Cooperative Oncology Group status, number of metastatic sites and antidrug antibody status) were evaluated. Concentration-time data of PF-05280014 and trastuzumab-EU were adequately described by a two-compartment model with first-order elimination, with inter-individual variability (IIV) on clearance (CL), volumes of distribution in central compartment (V1) and peripheral compartments, and intercompartment clearance. Similar estimated PK parameters and IIV were obtained for both treatments. For PF-05280014 and trastuzumab-EU, baseline body weight was an influential covariate on CL and V1; the magnitude was comparable between treatments. PK was consistent between the limited number of Japanese and non-Japanese patients for both compounds. CONCLUSIONS:PF-05280014 and trastuzumab-EU had similar PK parameters and influential PK covariates in patients with HER2-positive mBC. These results provided further evidence in patients for PK similarity between PF-05280014 and trastuzumab-EU. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov, NCT01989676.

Project description:BackgroundTrastuzumab improves survival in the adjuvant treatment of HER-positive breast cancer, although combined therapy with anthracycline-based regimens has been associated with cardiac toxicity. We wanted to evaluate the efficacy and safety of a new nonanthracycline regimen with trastuzumab.MethodsWe randomly assigned 3222 women with HER2-positive early-stage breast cancer to receive doxorubicin and cyclophosphamide followed by docetaxel every 3 weeks (AC-T), the same regimen plus 52 weeks of trastuzumab (AC-T plus trastuzumab), or docetaxel and carboplatin plus 52 weeks of trastuzumab (TCH). The primary study end point was disease-free survival. Secondary end points were overall survival and safety.ResultsAt a median follow-up of 65 months, 656 events triggered this protocol-specified analysis. The estimated disease-free survival rates at 5 years were 75% among patients receiving AC-T, 84% among those receiving AC-T plus trastuzumab, and 81% among those receiving TCH. Estimated rates of overall survival were 87%, 92%, and 91%, respectively. No significant differences in efficacy (disease-free or overall survival) were found between the two trastuzumab regimens, whereas both were superior to AC-T. The rates of congestive heart failure and cardiac dysfunction were significantly higher in the group receiving AC-T plus trastuzumab than in the TCH group (P<0.001). Eight cases of acute leukemia were reported: seven in the groups receiving the anthracycline-based regimens and one in the TCH group subsequent to receiving an anthracycline outside the study.ConclusionsThe addition of 1 year of adjuvant trastuzumab significantly improved disease-free and overall survival among women with HER2-positive breast cancer. The risk-benefit ratio favored the nonanthracycline TCH regimen over AC-T plus trastuzumab, given its similar efficacy, fewer acute toxic effects, and lower risks of cardiotoxicity and leukemia. (Funded by Sanofi-Aventis and Genentech; BCIRG-006 ClinicalTrials.gov number, NCT00021255.).

Dataset Information

Efficacy and safety of CT-P6 versus reference trastuzumab in HER2-positive early breast cancer: updated results of a randomised phase 3 trial.

Publications

Efficacy and safety of CT-P6 versus reference trastuzumab in HER2-positive early breast cancer: updated results of a randomised phase 3 trial.

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