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 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 (ESR1) 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.

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0:08 | 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.

0:40 | 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.

1:15 | The most interesting finding from the ELAINE-1 clinical trial was the fact that when we looked at a pharmacodynamic signal in these ESR1 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.

1:55 | We were most interested in the Y537S 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 Y537S 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.