Loading
The trial that made trastuzumab standard: adding the HER2 antibody to chemotherapy slowed progression and prolonged life in women whose breast cancers overexpressed HER2, at the cost of heart weakening when it was paired with anthracyclines.
This phase 3 trial randomised 469 women with previously untreated HER2-overexpressing metastatic breast cancer to chemotherapy (an anthracycline plus cyclophosphamide, or paclitaxel for those who had received adjuvant anthracycline) with or without trastuzumab. Adding trastuzumab lengthened the time to progression and raised the response rate, and it improved overall survival despite two thirds of the chemotherapy-alone group receiving trastuzumab after progression. Cardiac dysfunction was markedly more frequent when trastuzumab was combined with the anthracycline, which is why the two are not given together today.
This was the first proof that a monoclonal antibody against a growth receptor could extend life in a common solid tumour, and it created HER2-positive breast cancer as a disease treated differently from the rest. Its cardiac finding shaped every later HER2 regimen, which pair trastuzumab with taxanes rather than anthracyclines.
ToGA made gastric cancer the second disease treated by HER2 status and introduced gastric-specific HER2 scoring. It is the base on which trastuzumab deruxtecan and pembrolizumab combinations in HER2-positive gastric cancer have built.
This study confirmed HER2 as a prognostic marker and a therapeutic target, showed that immunohistochemistry could identify the patients, and extended the target to ovarian cancer. It set up the clinical development of trastuzumab and the HER2 testing that every breast cancer now receives.
Every HER2 test, every trastuzumab prescription and the whole HER2-positive breast cancer category trace back to this observation. It is the model for how a genomic marker of bad prognosis became a drug target and then the basis for one of the largest survival gains in solid tumour oncology.
Shares Dennis J. Slamon, Trastuzumab, HER2, HER2-positive breast cancer.
Shares ToGA (Bang 2010): trastuzumab with chemotherapy for HER2-positive advanced gastric cancer, Trastuzumab, Roche / Genentech, HER2.
Shares Trastuzumab, Roche / Genentech, Paclitaxel / nab-paclitaxel, HER2-positive breast cancer.
Shares ToGA (Bang 2010): trastuzumab with chemotherapy for HER2-positive advanced gastric cancer, Trastuzumab, HER2.
Shares Trastuzumab, HER2, HER2-positive breast cancer.
Shares Slamon 1989: HER2/neu in human breast and ovarian cancer, HER2, HER2-positive breast cancer.
Shares Trastuzumab, Roche / Genentech, HER2, HER2-positive breast cancer.
Shares Trastuzumab, HER2, HER2-positive breast cancer.