Eli Lilly and Company recently announced that the US Food and Drug Administration (FDA) has granted full approval to Inluriyo (imlunestrant), an oral Estrogen Receptor (ER) antagonist, in combination with Verzenio (abemaciclib), a CDK4/6 inhibitor, for the treatment of adults ER+, Human Epidermal Growth Factor (HEGF) receptor 2-negative (HER2–), ESR1-mutated locally advanced or metastatic breast cancer, as detected by an FDA-authorised test, with disease progression following at least 1 line of endocrine therapy. The approval is based on the proven clinical benefit of switching to Inluriyo in combination with Verzenio at clinical progression as observed in the phase 3 EMBER-3 trial.

Jacob Van Naarden, Executive Vice President and President, Lilly Oncology, said, "In less than a year since its approval, Inluriyo is the leading treatment option for people with ER+, HER2–, ESR1m metastatic breast cancer, now reaching over half of all patients starting an oral SERD. Today's full approval extends what Inluriyo in combination with Verzenio can do for patients, with a regimen that has confirmed benefit, is aligned to the clinically proven treatment paradigm of changing therapy at clinical progression, and doesn't introduce burdensome monitoring requirements for patients or physicians. In fact, all available evidence suggests that switching endocrine therapy and CDK4/6 inhibitor at clinical progression improves patient outcomes more than switching therapy earlier. Utilising this evidence-based practice spares early exposure to additional side effects, reduces patient anxiety from unnecessary testing, and mitigates avoidable costs to the healthcare system."

This full FDA approval is based on the results of the phase 3 EMBER-3 trial in patients with metastatic breast cancer whose tumors harbor an ESR1 mutation (n=159). Patients received Inluriyo (n=92) or Inluriyo in combination with Verzenio (n=67) after an Aromatase Inhibitor (AI), with or without a CDK4/6 inhibitor, in either the adjuvant or metastatic setting. Among patients with ESR1-mutated MBC, Inluriyo in combination with Verzenio doubled median Progression-Free Survival (PFS) versus Inluriyo alone, with a median PFS of 11.1 months versus 5.5 months (HR=0.53 [95 percent CI, 0.35-0.80]).

Komal Jhaveri, MD, FACP, FASCO, Associate Attending Breast Medicine and Early Drug Development Services, Section Head—Endocrine Therapy Research Program, Memorial Sloan Kettering Cancer Center, and principal investigator for the EMBER-3 and EMBER-4 trials, said, "We have an urgent need for effective and safe treatment options for patients with disease progression on adjuvant or first-line therapy. Combining therapies that work on two distinct drivers of tumor growth—the estrogen receptor and CDK4/6—is an important strategy to help address treatment resistance. In EMBER-3, switching both the endocrine therapy and CDK 4/6 inhibitor, for the majority of patients, to imlunestrant plus abemaciclib at disease progression achieved a median Progression-Free Survival of 11.1 months and a safety profile consistent with that of each medicine individually, establishing a meaningful new treatment option."

The Inluriyo label contains a warning and precaution for embryo-fetal toxicity.  

The Verzenio label contains warnings and precautions for severe diarrhea, neutropenia, Interstitial Lung Disease (ILD)/pneumonitis, hepatotoxicity, venous thromboembolism, embryo-fetal toxicity, and increased serum creatinine without affecting renal function.

In EMBER-3, the majority of Adverse Events (AEs) with Inluriyo in combination with Verzenio were Grade 1-2. The most common (≥10 percent) adverse reactions, including laboratory abnormalities, were decreased neutrophils, diarrhea, decreased hemoglobin, decreased lymphocytes, nausea, decreased platelets, fatigue, increased triglycerides, infections, increased AST, increased creatinine, increased ALT, vomiting, musculoskeletal pain, abdominal pain, decreased appetite, increased cholesterol, rash, cough, headache, and decreased weight. Permanent discontinuation of Inluriyo alone due to adverse reactions in the combination arm occurred in 1 percent of patients, and permanent discontinuation of Verzenio alone in the combination arm occurred in 3.4 percent of patients.

This marks the second FDA approval for Inluriyo in less than a year, following its September 2025 approval as monotherapy for the treatment of adults with ER+, HER2–, ESR1-mutated metastatic breast cancer whose disease progressed after at least one line of Endocrine Therapy (ET).

Inluriyo is also being studied in the phase 3 EMBER-4 trial (NCT05514054) in the adjuvant setting for people with ER+, HER2– early-stage breast cancer at increased risk of recurrence following Standard of Care (SoC) endocrine therapy, including CDK4/6 inhibitors. EMBER-4 is the largest adjuvant oral SERD clinical trial, with more than 8,000 patients enrolled worldwide across 650+ sites in 30+ countries. Initial results are anticipated in 2027.

Inluriyo in combination with Verzenio is now available in the US.