Matthew P. Goetz, MD

Matthew P. Goetz, MD, consultant, Division of Medical Oncology, Department of Oncology, Mayo Clinic, discusses the findings from the ELAINE-1 trial (NCT03781063).

In the study, investiagtors evaluated lasofoxifene vs fulvestrant (Faslodex) in patients with locally advanced/metastatic breast cancer and an estrogen receptor 1 (

) mutation. Patients must have progressed on aromatase and CDK 4/6 inhibitors.

According to findings presented at ESMO 2022, 

treatment with lasofoxifene elicited a durable complete response

 (CR) which could be characterized as complete clinical remission.

The results of the trial demonstrated that lasofoxifene led to a median progression-free survival of a little over 6 months compared with fulvestrant, which had a median progression-free survival of 4 months. This corresponded to a hazard ratio of 0.699 and this result was not statistically significant but a clear signal that lasofoxifene may have some benefit.

Some of the secondary end points that were looked at also provided evidence for that signal, including overall response rates where lasofoxifene led to a response rate of greater than 13% vs fulvestrant at a little less than 3%. Similarly, clinical benefit rate was also prolonged. Again, both the response rate and clinical benefit rate did not meet statistical significance, but these are favorable signals are something that should be evaluated in larger studies.

The most interesting finding from the ELAINE-1 clinical trial was the fact that when we looked at a pharmacodynamic signal in these 

 mutations in the mutant allele fraction, what we found was that lasofoxifene was effectively targeting these mutant allele fractions with a dramatic decrease of all the variants with a greater decrease with lasofoxifene than with fulvestrant.

 alteration, which we know is a very difficult alteration to treat. Clinically, this mutant in was a stratification factor in ELAINE-1. What we found was that in patients treated with lasofoxifene, there was a dramatic decrease in the 

 alteration at the 8-week mark. In contrast with fulvestrant, there was an increase which give us good evidence of what I would say is an on-target effect of lasofoxifene. It provides further evidence that this drug should be studied further in combination with other targeted therapies.

Videos

Matthew P. Goetz, MD, consultant, Division of Medical Oncology, Department of Oncology, Mayo Clinic, discusses the findings from the ELAINE-1 trial.

Durable CR With Lasofoxifene in ESR1+, ER+/HER2- Metastatic Breast Cancer

Matthew P. Goetz, MD, consultant, Division of Medical Oncology, Department of Oncology, Mayo Clinic, discusses how genomic assays can help identify patients with estrogen receptor (ER)positive breast cancer who will benefit from the addition of chemotherapy to endocrine therapy.

There are a number of considerations when selecting a genomic assay for these patients, says Goetz. For the past 10 to 15 years, the focus has been on identifying patients with ER-positive disease who could do well with endocrine therapy alone versus those who need the addition of chemotherapy to treatment. A number of genomic assays are now in development to help identify those patients that can be de-escalated from chemotherapy.

Over the last few years, a number of different clinical trials have helped in identifying which genomic assays are most useful in this setting, and recent data have confirmed the utility of these assays in patient selection. Data suggest that the most useful assay is the Oncotype DX test, which assigns patients a recurrence score.

Matthew P. Goetz, MD, discusses how genomic assays can help identify patients with ER&ndash;positive breast cancer who will benefit from the addition of chemotherapy to endocrine therapy.

Matthew P. Goetz, MD | Authors

Articles

Durable CR With Lasofoxifene in ESR1+, ER+/HER2- Metastatic Breast Cancer

Genomic Assays Impact Treatment Decisions in Patients With ER+ Breast Cancer