Sermonix’s SERM proves itself in extended follow-up trial in combination with CDK4/6 inhibitor in ELAINE 2 trial

ELAINE 2 trial Result

We have heard a lot about SERDs, but we also have a selective estrogen receptor modulator (SERM) that can effectively target ESR1 mutants. The only SERM for the treatment of ESR1-mutated ER+/HER2- metastatic breast cancer in the second-line setting is lasofoxifene. Lasofoxifene is being investigated as a potent, bioavailable selective estrogen receptor modulator with a differentiated safety profile that could prove useful in treating postmenopausal women and premenopausal women on ovarian suppression with locally advanced or metastatic ER+ breast cancer. According to the data presented at the ASCO 2023, as of April 2023, 6 of the 29 enrolled patients were continuing the treatment, 17 had disease progression, and 1 had discontinued due to AEs.

Most frequently detected ESR1 mutations at baseline (%)









Polyclonal ESR1 mutations


In terms of safety results, the lasofoxifene/abemaciclib combination was well tolerated with primarily grade 1/2 treatment-emergent adverse events (TRAEs) (most commonly diarrhea, nausea, fatigue, and vomiting). Apart from that, the grade 3 and above reported TRAEs consist of anemia (10.3%), hypokalemia (10.3%), fall (6.9%), and others. The other promising outcome that was revealed during the study was that no deaths occurred during the treatment. 

In terms of efficacy results, lasofoxifene/abemaciclib was associated with a clinically meaningful median PFS (progression free survival) of 13 months, followed by a CBR (clinical benefit rate) of 65.5%, and an ORR of 55.6%. The median overall survival was not estimable at the time of the study. Apart from that, the PFS rate for 6, 12, and 18 months was 76.1%, 56.1%, and 38.8%, respectively. Lasofoxifene/Abemaciclib combination defies endocrine resistance-associated alterations, sustaining robust therapeutic activity.

KOL insights

“Sermonix is pleased that the combination of lasofoxifene and abemaciclib, which demonstrated compelling anti-tumor activity in ELAINE-2, continued to be well-tolerated when observed through a longer patient follow-up.” –Expert Opinion.


ESR1 mutations rarely exist in primary tumors (~ 1%) but are relatively common (10–50%) in metastatic, endocrine therapy-resistant cancers and are associated with a shorter progression-free survival. However, with the exposure of patients with breast cancer to aromatase inhibitors (AIs) in adjuvant and metastatic cancer, the ESR1 mutation increases at a significant rate, leading to resistance to AIs. Based on the above findings, the extended ELAINE 2 follow-up study confirmed the favorable tolerability and clinically significant effectiveness of the lasofoxifene/abemaciclib combination in women with mESR1, ER+/HER2- metastatic breast cancer who experienced disease progression on endocrine therapy and CDK4/6 inhibitors. Encouragingly, reductions in mESR1 ctDNA indicated successful engagement of lasofoxifene's target. Moving ahead, a confirmatory Phase III study (ELAINE 3; NCT05696626) will compare lasofoxifene/abemaciclib with fulvestrant/abemaciclib. Lastly, the promising ELAINE 2 findings validate the potential of the lasofoxifene and abemaciclib combination as a game-changing therapeutic approach, filling an urgent treatment gap for mESR1 breast cancer and revolutionizing clinical practice