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Whether HER2-positive non-breast cancers are candidates for treatment with Ado-trastuzumab emtansine?

ABSTRACT: The National Comprehensive Cancer Network (NCCN) has recommended Ado-trastuzumab emtansine (T-DM1) as a preferred agent for patients with human epidermal growth factor receptor-2 (HER2)-positive metastatic breast cancer and prior trastuzumab therapy. Overexpression of HER2 was reported in other cancer types such as bladder, gastric and urogenital carcinosarcomas similar to what is discovered in breast cancer. Some preclinical studies demonstrated the potential anti-tumor effects of T-DM1 in HER2-positive non-breast cancers. There is a paucity of data over the clinical evaluation of T-DM1 in human studies of non-breast cancer patients. We review some preclinical and ongoing clinical studies that assessed the efficacy of T-DM1 administration in the treatment of non-breast HER2 positive malignancies. Performing large and well-designed trials in this area is matter of interest and highly recommended.

SUBMITTER: Moghaddas A

PROVIDER: S-EPMC5084478 | biostudies-other | 2016 Oct-Dec

REPOSITORIES: biostudies-other

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Whether HER2-positive non-breast cancers are candidates for treatment with Ado-trastuzumab emtansine?

Moghaddas Azadeh A Borhani Ali A

Journal of research in pharmacy practice 20161001 4

The National Comprehensive Cancer Network (NCCN) has recommended Ado-trastuzumab emtansine (T-DM1) as a preferred agent for patients with human epidermal growth factor receptor-2 (HER2)-positive metastatic breast cancer and prior trastuzumab therapy. Overexpression of HER2 was reported in other cancer types such as bladder, gastric and urogenital carcinosarcomas similar to what is discovered in breast cancer. Some preclinical studies demonstrated the potential anti-tumor effects of T-DM1 in HER2 ...[more]

PMID: 27843957

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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.).

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.).

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Whether HER2-positive non-breast cancers are candidates for treatment with Ado-trastuzumab emtansine?

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Whether HER2-positive non-breast cancers are candidates for treatment with Ado-trastuzumab emtansine?

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