Newest trial fulvestrant

Bidard and colleagues conducted the multicenter, open-label PADA-1 trial to assess the clinical benefit of switching therapy — from a first-line aromatase inhibitor-palbociclib regimen to a fulvestrant-palbociclib combination — upon detection of a rising ESR1 mutation via circulating tumor DNA.

The study included patients with hormone receptor-positive, HER2-negative metastatic breast cancer who had received no prior therapy for metastatic breast cancer in the absence of aromatase inhibitor-resistance.

Patients assigned to continue initial therapy could cross over to fulvestrant-palbociclib following tumor progression. After a median Researchers randomly assigned 84 patients to the standard group and 88 patients to the experimental group. Researchers reported significantly longer median PFS among patients who switched to fulvestrant-palbociclib than those who remained on the aromatase inhibitor-palbociclib regimen Seventy patients randomly assigned to continue the aromatase inhibitor-palbociclib regimen developed disease progression, and 47 crossed over to fulvestrant-palbociclib.

After median follow-up Researchers reported median second PFS in the crossover cohort of 3. This finding supports prior studies that suggested limited benefit of fulvestrant as second-line therapy, Bidard said.

Additional studies are needed to yield insights about the clinical features of ESR1 -mutated tumors, as well as to better predict which patients may develop these mutations, researchers wrote. Researchers acknowledged two limitations to their study: The digital droplet polymerase chain reaction assay used to detect ESR1 mutations is not certified for clinical use in the United States, and the investigators who calculated PFS were not blinded to the treatment group patients were assigned to in the randomization stage.

This is a tremendously exciting study, as it is the first in breast cancer to show that switching therapy based on genomic findings prior to clinical progression improves outcomes for patients with metastatic breast cancer. However, patients who switched to fulvestrant based on standard clinical progression had only a PFS of 3. The implication is that early detection of resistant disease — and switching therapy based on this finding — actually makes a difference, and this had never been shown before.

There are other ongoing trials investigating this finding, which hopefully will lend support to this approach. Most patients had lobular Patients received a median of 5 range, prior regimens for locally advanced or metastatic disease and all received prior endocrine therapy.

Twenty-seven Patients had other No patient had mixed ductal and lobular disease. Patients received a median of 3. Diarrhea was the most common all-grade treatment-emergent adverse event, appearing in There was no incidence of grade 4 diarrhea in either group but Abstract GS Patients who progress on this standard therapy may then be treated with the HER2-targeted tyrosine kinase inhibitor TKI lapatinib in combination with the chemotherapeutic capecitabine or with alternative HER2-targeted therapies, such as trastuzumab emtansine.

This may facilitate the development of treatment resistance, Dr. Xu noted. In addition, trastuzumab emtansine T-DM1 , which is the preferred regimen for second-line therapy after trastuzumab in many international guidelines, is not approved for metastatic disease in many countries. A prior phase II clinical trial found that pyrotinib plus capecitabine led to clinical responses in previously treated patients with HER2-positive metastatic breast cancer.

He noted that the results of the PHOEBE clinical trial led to the approval of pyrotinib in combination with capecitabine as second-line standard-of-care treatment for HER2-positive metastatic breast cancer in China. GS Primary results of the cTRAK TN trial: A clinical trial utilising ctDNA mutation tracking to detect minimal residual disease and trigger intervention in patients with moderate and high risk early stage triple negative breast cancer.