Comparative effectiveness of trastuzumab emtansine versus lapatinib plus chemotherapy for HER2+ metastatic breast cancer

Ramagopalan, Sreeram; Pisoni, Riccardo; Zenin, Aleksandr; Rathore, Lokendra Singh; Ray, Joshua; Sammon, Cormac

doi:10.2217/cer-2020-0201

Cited by 7 publications

(4 citation statements)

References 10 publications

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“…On the other hand, the use of T-DM1 became more than twice as frequent as previously observed, highlighting the strategy shift from lapatinib to T-DM1. This is in agreement with the EMILIA trial [ 16 ] results as well as with an RWE study using data from Flatiron Health database that showed a longer OS for patients treated with T-DM1 versus Lapatinib as second-line therapy [ 24 , 25 ]. Nonetheless, trastuzumab alone or in combination with other targeted therapies or chemotherapies remains the preferred choice as third-line in Canada.…”

Section: Discussionsupporting

confidence: 88%

Third-line treatment patterns in HER2-positive metastatic breast cancer: a retrospective analysis of real-world data in Canada

Gambaro,

Groleau,

McNamara

et al. 2023

J. pharm. pharm. sci.

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There is an increasing demand for real-world data pertaining to the usage of cancer treatments, especially in settings where no standard treatment is specifically recommended. This study presents the first real-world analysis of third-line treatment patterns in HER2-positive metastatic breast cancer (mBC) patients in Canada. The purpose was to assess evolution of clinical practice and identify unmet needs in post-second-line therapy. Retrospective data from medical records of 66 patients who received third-line treatment before 31st October 2018, and data from 56 patients who received third-line treatment after this date, extracted from the Personalize My Treatment (PMT) cancer patient registry, were analyzed. In the first cohort, the study revealed heterogeneity in the third-line setting, with trastuzumab, lapatinib, and T-DM1 being the main treatment options. Even though data were collected before the wide availability of tucatinib, neratinib and trastuzumab deruxtecan in Canada, the PMT cohort revealed the emergence of new therapeutic combinations and a shift from lapatinib usage to T-DM1 choice was observed. These findings underscore the evolving nature of third-line treatment strategies in Canada, a facet that is intrinsically tied to the availability of new drugs. The absence of a consensus on post-second-line treatment highlights the pressing need for more efficient therapeutic alternatives beyond the currently available options. This study not only offers valuable insights into the present landscape of third-line treatment in Canada but validates the significance and effectiveness of the PMT registry as a tool for generating pan-Canadian real-world evidence in oncology and its capacity to provide information on evolution of therapeutic practices.

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Section: Discussionsupporting

confidence: 88%

Third-line treatment patterns in HER2-positive metastatic breast cancer: a retrospective analysis of real-world data in Canada

Gambaro,

Groleau,

McNamara

et al. 2023

J. pharm. pharm. sci.

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“… 23 , 25 , 27 , 28 Although the Flatiron/FMI database does not represent a traditional clinical trial comparator, it has previously demonstrated concordance with clinical trial data and has been used as the data source for oncology research across different therapies and indications, including atezolizumab for NSCLC, trastuzumab and lapatinib for human epidermal growth factor receptor 2–positive metastatic breast cancer, and durvalumab and chemotherapy for metastatic urothelial carcinoma. 32 - 34 The dates selected for the Flatiron/FMI patient data (January 2011 to December 2019) were after approval of larotrectinib by the United States and the European Union, but before widespread acceptance of larotrectinib as a SoC for TRK fusion-positive cancers. Exclusion of patients previously treated with TRK inhibitors ensured that the MAIC comparison would restrict the comparison to larotrectinib versus non–TRK-inhibitor SoC.…”

Section: Discussionmentioning

confidence: 99%

Survival Outcomes of Patients With Tropomyosin Receptor Kinase Fusion-Positive Cancer Receiving Larotrectinib Versus Standard of Care: A Matching-Adjusted Indirect Comparison Using Real-World Data

Bokemeyer

Paracha

Lassen

et al. 2023

JCO Precision Oncology

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PURPOSE Larotrectinib, a highly specific tropomyosin receptor kinase (TRK) inhibitor, previously demonstrated high response rates in single-arm trials of patients with TRK fusion-positive cancer, but there are limited data on comparative effectiveness against standard-of-care (SoC) regimens used in routine health care practice, before widespread adoption of TRK inhibitors as SoC for TRK fusion-positive cancers. Matching-adjusted indirect comparison, a validated methodology that balances population characteristics to facilitate cross-trial comparisons, was used to compare the overall survival (OS) of larotrectinib versus non–TRK-inhibitor SoC. MATERIALS AND METHODS Individual patient data from three larotrectinib trials (ClinicalTrials.gov identifiers: NCT02122913 , NCT02637687 , and NCT02576431 ) were compared with published aggregate real-world data from patients with locally advanced/metastatic TRK fusion-positive cancer identified in the Flatiron Health/Foundation Medicine database. OS was defined as the time from advanced/metastatic disease diagnosis to death. After matching population characteristics, the analyses included (1) a log-rank test of equality to test whether the two groups were similar before larotrectinib initiation; and (2) estimation of treatment effect of larotrectinib versus non–TRK-inhibitor SoC. These analyses are limited to prognostic variables available in real-world data. RESULTS Eighty-five larotrectinib patients and 28 non-TRK-inhibitor SoC patients were included in the analyses. After matching, log-rank testing showed no difference in baseline characteristics between the two groups ( P = .31). After matching, larotrectinib was associated with a 78% lower risk of death, compared with non–TRK-inhibitor SoC (adjusted hazard ratio, 0.22 [95% CI, 0.09 to 0.52]; P = .001); median OS was 39.7 months (95% CI: 16.4, NE [not estimable]) for larotrectinib and 10.2 months (95% CI: 7.2, 14.1) for SoC. CONCLUSION Matching-adjusted indirect comparison analyses suggest longer OS with larotrectinib, compared with non–TRK-inhibitor SoC, in adult patients with TRK fusion-positive cancer.

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“…T-DM1 is a combination of trastuzumab and a chemotherapeutic drug, metanephrine, that retains the activity of trastuzumab monoclonal antibody while delivering potent anti-tumor activity to HER-2 overexpressing tumor cells.According to EMILIA, T-DM1 improved PFS and OS over capecitabine combined with lapatinib in patients with HER-2-positive advanced or MBC treated with trastuzumab and paclitaxel, while Ramagopalan SV et al conducted a real-world study based on the US FH database, and the results further supported T-DM1 therapy as a treatment option for patients with HER-2-positive advanced or MBC [30] . The significant efficacy and good safety of T-DM1 in the treatment of HER-2-positive advanced breast cancer was confirmed by Yan Bingxue et al [31] after performing Meta-analysis.…”

Section: T-dm1mentioning

confidence: 99%

Progress of targeted therapy for HER-2 positive breast cancer

2023

AJMHS

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Breast cancer is now the most common cancer worldwide, and human Epidermal GrowthFactor Receptor-2 (HER-2) positive breast cancer is more malignant, prone to recurrence and metastasis, and has a poor prognosis.However, the advent of trastuzumab monoclonal antibody, a targeted drug, has since improved the prognosis of patients, and a series of anti-HER-2 targeted drugs have since emerged, including pertuzumab monoclonal antibody, inetol monoclonal antibody, tyrosine kinase inhibitors (Neratinib, Lapatinib, Pyrrolitinib, Tucatinib), antibody drug conjugates SYD985), etc.This paper reviews the progress of targeted therapy for HER-2-positive breast cancer by different mechanisms of action as follows.

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Comparative effectiveness of trastuzumab emtansine versus lapatinib plus chemotherapy for HER2+ metastatic breast cancer

Cited by 7 publications

References 10 publications

Third-line treatment patterns in HER2-positive metastatic breast cancer: a retrospective analysis of real-world data in Canada

Third-line treatment patterns in HER2-positive metastatic breast cancer: a retrospective analysis of real-world data in Canada

Survival Outcomes of Patients With Tropomyosin Receptor Kinase Fusion-Positive Cancer Receiving Larotrectinib Versus Standard of Care: A Matching-Adjusted Indirect Comparison Using Real-World Data

Progress of targeted therapy for HER-2 positive breast cancer

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