Considering Elacestrant in ESR1+ Breast Cancer After CDK4/6 Inhibition
Paolo Tarantino, MD, PhD, discusses elacestrant as a treatment option for patients with ESR1-mutated metastatic breast cancer in the second line.
Paolo Tarantino, MD, PhD, medical oncologist and clinical fellow at Dana-Farber Cancer Institute, discusses elacestrant (Orserdu) as a well-tolerated treatment option for patients with hormone receptor (HR)-positive, HER2-negative metastatic breast cancer who have ESR1 mutations and have benefited from prior CDK4/6 inhibitors.
In terms of treatment options for CDK4/6 inhibitors, each has distinct adverse events (AEs). Tarantino suggests that elacestrant is one of the most well-tolerated options, particularly for patients with ESR1 mutations who have previously benefited from treatment with aromatase inhibitors and CDK4/6 inhibitors for 1 to 2 years.
ESR1 mutations are dynamic and more prevalent in metastatic settings than in the primary tumor, making retesting essential, ideally using circulating tumor DNA (ctDNA), according to Tarantino. For patients with ESR1 mutations and HR-positive disease, elacestrant is recommended due to its efficacy and good tolerance.
TRANSCRIPTION:
0:10 | In the second-line, after progression on CDK4/6 inhibitors, most of the treatment options that we have available have peculiar [AEs], and so we have hypoglycemia with alpelisib [Piqray], we have diarrhea with capivasertib [Truqap], and rash and mucositis and other [AEs] with everolimus. Each treatment has AEs—probably among these, although we have no head-to-head comparisons, elacestrant seems to be the best tolerated one.
0:39 | I think it's important to remember this treatment option and [utilize] it in the right patient population, remembering that for those patients who are found to have ESR1 mutations and have derived benefit from prior CDK4/6 inhibitors in 1 year, 1 year and a half, [or] even longer, at 2 years, I think it's a great option to consider elacestrant. Another important thing to remember is that ESR1 mutations are dynamic alterations, so [they] are very different from PIK3CA mutations, AKT and other mutations, even HER2. Most of the other mutations are found both in the primary tumor and the metastatic tissue and are mostly constant with slight changes in time.
1:22 | But ESR1 mutations are highly dynamic. Less than 1% of the primary tumors are ESR1 mutant, but this percentage becomes 30% to 40% in the metastatic setting after prior treatment with aromatase inhibitors and CDK4/6 inhibitors. Remember to retest to look for ESR1 mutation, ideally with ctDNA, which is the easiest, non-invasive, and most convenient test. If there is a ESR1 mutation in the patient who has HR-positive disease [and] has benefited from prior CDK4/6 inhibitors, consider elacestrant, which has demonstrated compelling efficacy and is also very well tolerated.
Post–PD-1 Data in Melanoma Offers Insight into IO Approaches
February 13th 2025During a Case-Based Roundtable® event, Thach-Giao Truong, MD, discussed goals and barriers to treatment when using combination immunotherapy for metastatic melanoma in the second article of a 2-part series.
Read More
