Dr Sardesai on Lasofoxifene Plus Abemaciclib in ESR1-Mutant, ER+/HER2– Breast Cancer

"This clinical trial offers an opportunity for patients to receive a targeted therapy like lasofoxifene along with abemaciclib, which is a very unique CDK4/6 inhibitor that has shown a clinical response beyond progression on frontline CDK4/6 therapy."

Sagar D. Sardesai, MBBS, breast medical oncologist, Division of Medical Oncology, The Ohio State University (OSU); member, Cancer Control Program, Ohio State University Comprehensive Cancer Center–James, discusses the phase 3 ELAINEIII trial (NCT05696626) evaluating lasofoxifene in combination with abemaciclib (Verzenio) for patients with ESR1-mutant, estrogen receptor (ER)–positive, HER2-negative locally advanced or metastatic breast cancer.

To enroll in this open-label, multicenter, global randomized study, patients must have received frontline therapy with an aromatase inhibitor and a CDK4/6 inhibitor other than abemaciclib and have tumors harboring an activating ESR1 mutation, a key eligibility criterion, Sardesai details. The study aims to compare the progression-free survival (PFS) outcomes of 2 treatment regimens: the oral next-generation selective estrogen receptor modulator and antagonist lasofoxifene combined with abemaciclib, vs fulvestrant (Faslodex) in combination with abemaciclib, he says.

Elacestrant (Orserdu) is currently the only FDA-approved endocrine therapy available for patients with ER-positive, HER2-negative metastatic breast cancer and ESR1 mutations, Sardesai states. Although elacestrant demonstrates meaningful clinical benefit in terms of survival and response rates for some patients, no approved combination regimens exist for this population, he notes. ELAINEIII represents a unique opportunity to assess targeted combination therapy with lasofoxifene, an oral agent with a novel mechanism of action, alongside abemaciclib, a CDK4/6 inhibitor that has demonstrated clinical activity beyond progression on frontline CDK4/6 inhibitor therapy, Sardesai explains.

Abemaciclib has distinct characteristics compared with other CDK4/6 inhibitors, as it has shown efficacy in patients whose disease progressed following prior CDK4/6-based therapy, Sardesai continues. By pairing abemaciclib with lasofoxifene, the trial explores a potentially more effective strategy for managing resistance driven by ESR1 mutations. This combination may offer patients prolonged disease control and clinical benefit compared with the current standard of fulvestrant and abemaciclib, Sardesai adds.

Positive outcomes from this study could provide an alternative therapeutic option and further define the role of lasofoxifene in combination with abemaciclib for this patient population, Sardesai concludes.