Inluriyo (imlunestrant)

Oral SERDs are reshaping the management of ESR1-mutant disease, with agents such as elacestrant and imlunestrant emerging as standard second-line options. However, primary resistance to SERD monotherapy remains substantial, highlighting the need for combination strategies. Future directions include ctDNA-guided approaches and expansion into earlier treatment settings.

The use of drug therapies such as imlunestrant that specifically target ESR1 mutations in advanced breast cancer cases reflects the incorporation of genetic biomarkers into routine clinical decision making...The further development of HRD and the viral onco-genes have widened the options available for a biomarker-based therapy. This chapter will provide an in-depth explanation of an Introduction to Cancer Biomarkers and new research developments.

Imlunestrant monotherapy had a similar safety profile between patients aged <65 and ≥65 years, while imlunestrant + abemaciclib had a similar safety profile to other abemaciclib+ET combinations in both age groups. Imlunestrant and imlunestrant + abemaciclib provide effective, convenient oral therapy with a favorable and manageable safety profile for patients with ER+, HER2- ABC with recurrence/progression on/after ET.

P1/2, N=880, Recruiting, Eli Lilly and Company | N=178 --> 880

GHS/QoL and function were maintained across treatment arms, despite a higher incidence of diarrhea in the imlunestrant-abemaciclib group. These PRO findings complement the efficacy and safety results from EMBER-3 and further support the favorable risk-benefit profile of imlunestrant, either as oral monotherapy or in combination with abemaciclib, in patients with advanced breast cancer.

In this ITC analysis of patient-level data from three phase III trials, although not powered for formal hypothesis testing, the all-oral targeted combination therapy imlunestrant + abemaciclib showed a consistent numerical reduction in the risk of disease progression or death compared with fulvestrant + abemaciclib in patients with ER-positive/HER2-negative ABC previously treated with endocrine therapy ± CDK4/6i.

Key 2025 findings (50 clinical trials) include: (1) confirmation of overall survival benefit with adjuvant CDK4/6 inhibitors in HR+/HER2- early breast cancer (monarchE: HR = 0.842, p = 0.0273); (2) establishment of trastuzumab deruxtecan (T-DXd) as a new standard in high-risk HER2+ early disease (DESTINY-Breast05: IDFS HR = 0.47) and first-line metastatic settings (DESTINY-Breast09: PFS HR = 0.58); (3) validation of TROP2-directed ADCs as first-line therapy for metastatic triple-negative breast cancer (ASCENT-03: PFS HR = 0.62; BEGONIA: ORR 79%); (4) paradigm shift to proactive, liquid biopsy-guided therapy switching (SERENA-6: PFS HR = 0.44); (5) updated efficacy and safety of the oral SERD imlunestrant from the EMBER-3 trial, supporting its role in ESR1-mutated advanced breast cancer and in combination with abemaciclib; (6) confirmation of long-term survival benefit for neoadjuvant carboplatin in early TNBC and new positive adjuvant data; (7) pivotal advances in HER2+ metastatic disease sequencing with tucatinib and T-DXd; (8) evidence supporting optimized adjuvant endocrine therapy in HER2+/HR+ early disease; and (9) emergence of novel agents with improved therapeutic indices, including PROTAC degraders, oral SERDs, and mutant-selective PI3K inhibitors. Unifying themes include biomarker-driven personalization, strategic treatment sequencing, management of unique toxicities, and emphasis on patient-reported outcomes. Future challenges include optimizing treatment integration, managing financial toxicity, and ensuring equitable global access.

P2, N=189, Not yet recruiting, Fudan University

P3, N=8000, Active, not recruiting, Eli Lilly and Company | Recruiting --> Active, not recruiting

P1, N=193, Active, not recruiting, Eli Lilly and Company | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026

P2, N=600, Not yet recruiting, Eli Lilly and Company | Trial completion date: Jan 2029 --> Dec 2029