Updated data for Lilly's Inluriyo reinforce efficacy results as monotherapy and in combination with Verzenio® in ER+, HER2- advanced breast cancer

As monotherapy, imlunestrant demonstrated an 11.4-month numeric improvement in median OS versus endocrine therapy in patients with ESR1-mutated disease

In all patients, the imlunestrant plus abemaciclib combination achieved a median PFS of 10.9 months, demonstrated a favorable OS trend, and extended time to chemotherapy by more than a year

These data were published simultaneously in Annals of Oncology and will be presented today at the 2025 San Antonio Breast Cancer Symposium

Eli Lilly and Company (NYSE: LLY) today announced updated results from the Phase 3 NCT04975308%25253Fterm%25253DLY3484356%25252520EMBER3%252526rank%25253D1%2526a%253DEMBER-3%252Bstudy%26a%3DEMBER-3%2Bstudy&a=EMBER-3+study" target="_blank" rel="nofollow">EMBER-3 study of Inluriyo (imlunestrant), an oral estrogen receptor antagonist, in patients with estrogen receptor positive (ER+), human epidermal growth factor receptor 2–negative (HER2–) advanced or metastatic breast cancer (MBC), whose disease progressed on a prior aromatase inhibitor (AI), with or without a CDK46 inhibitor. As monotherapy, imlunestrant demonstrated a clinically meaningful 38% reduction in the risk of progression or death (median PFS 5.5 vs 3.8 months; HR=0.62 [95% CI 0.47–0.82]; nominal p=0.0007) and demonstrated an 11.4-month improvement in median OS (34.5 vs 23.1 months; HR=0.60 [95% CI 0.43–0.86]; p=0.0043; boundary for significance not met) versus endocrine therapy, in patients with ESR1-mutated disease. In all patients, imlunestrant plus abemaciclib reduced the risk of progression or death by 41% versus imlunestrant alone, demonstrated a favorable OS trend and numerically delayed time to chemotherapy (TTC) by more than a year.

These results were published in Annals of Oncology and will be shared in a late-breaking oral presentation at the San Antonio Breast Cancer Symposium (SABCS) today, Friday, December 12, at 10:45 AM CT / 11:45 AM ET.

"Following the recent FDA approval of Inluriyo as monotherapy, these updated data demonstrate continued clinically meaningful benefit—both for patients receiving monotherapy and those receiving the combination with abemaciclib—and further reinforce its role in this treatment setting," said Jacob Van Naarden, executive vice president and president, Lilly Oncology. "Given the important role of CDK4/6 inhibitors in treating ER+, HER2– metastatic breast cancer, we're encouraged by the potential of an all-oral combination with imlunestrant and abemaciclib and have submitted these combination data for U.S. regulatory review in ESR1-mutated MBC."

Results for the imlunestrant plus abemaciclib combination were consistent with previous efficacy results and demonstrated durable benefit across efficacy endpoints, regardless of ESR1 mutation status. In all patients, median PFS was nearly doubled versus imlunestrant alone (10.9 vs 5.5 months; HR=0.59 [95% CI 0.47–0.74]; nominal p<0.0001), and a favorable OS trend was observed (HR=0.82 [95% CI 0.59–1.16]), with continued separation of survival curves. Median TTC was numerically extended by more than a year (27.8 vs 15.5 months) versus imlunestrant alone. In patients with ESR1-mutated disease, median PFS was extended to 11.0 months versus 5.6 months with imlunestrant alone (HR=0.55 [95% CI 0.41–0.74]; nominal p<0.001). Notably, most patients (65%) in the combination arm had previously received a CDK4/6 inhibitor.

"With an additional year of follow-up, these results strengthen the case for imlunestrant-based regimens in ER+, HER2– metastatic breast cancer," said Komal Jhaveri, MD, FACP, FASCO, Associate Attending Breast Medicine and Early Drug Development Services, section head of Endocrine Therapy Research Program at Memorial Sloan Kettering Cancer Center, and one of the study's principal investigators. "The median progression-free survival of 11 months is among the longest we've seen in this population, and just as importantly, patients are living longer without needing chemotherapy."

Safety across imlunestrant-based regimens was consistent with previous reports, and no new safety signals were observed with this additional follow-up. Follow-up for OS is ongoing, and additional analyses are planned as data mature.

Imlunestrant is also being investigated in the adjuvant setting in people with ER+, HER2– early breast cancer with an increased risk of recurrence. The Phase 3 EMBER-4 trial completed enrollment of approximately 8,000 patients following two to five years of adjuvant endocrine therapy in the context of the established CDK4/6i standard of care.

About EMBER-3
EMBER-3 is a Phase 3, randomized, open-label study of imlunestrant, investigator's choice of endocrine therapy, and imlunestrant in combination with abemaciclib in patients with ER+, HER2– locally advanced or metastatic breast cancer whose disease has recurred or progressed during or following an aromatase inhibitor (AI) therapy with or without a CDK 4/6 inhibitor. The trial enrolled 874 adult patients, 32% of which enrolled from the adjuvant setting into first-line treatment of MBC and 64% as second-line treatment following progression on initial therapy for MBC. Enrolled trial participants were randomized between imlunestrant, investigator's choice of fulvestrant or exemestane, or plus abemaciclib. Randomization was stratified by prior CDK4/6 inhibitor use, the presence of visceral metastases and geographic region. Patients enrolled as first line (1L) treatment for ABC (32%), following disease recurrence on or within 12 months of completing adjuvant AI, with or without CDK4/6 inhibitor for early breast cancer (EBC), or as second line (2L) treatment for ABC (64%), following progression on AI, with or without CDK4/6 inhibitor as initial therapy for ABC. Primary endpoints were investigator-assessed PFS of imlunestrant versus SOC ET therapy in patients with ESR1 mutations, imlunestrant versus SOC ET in all patients, and Imlunestrant plus abemaciclib versus imlunestrant in all patients. More information on the EMBER-3 study can be found on clinicaltrials.gov.

About Metastatic/Advanced Breast Cancer
Metastatic/advanced breast cancer (ABC) is a cancer that has spread from the breast tissue to other parts of the body. Locally advanced breast cancer means the cancer has grown outside the organ where it started but has not yet spread to other parts of the body.¹ Of all high risk early-stage breast cancer cases diagnosed in the U.S., approximately 30% will become metastatic² and an estimated 6-10% of all new breast cancer cases are initially diagnosed as being metastatic.³ Survival is lower among women with a more advanced stage of disease at diagnosis: five-year relative survival is 99% for localized disease, 86% for regional/locally advanced disease, and 30% for metastatic/advanced disease.⁴ Other factors, such as tumor size, also impact five-year survival estimates.⁴

About Breast Cancer
Breast cancer is the second most commonly diagnosed cancer worldwide (following lung cancer), according to GLOBOCAN. The estimated 2.3 million new cases indicate that close to 1 in every 4 cancers diagnosed in 2022 is breast cancer. With approximately 666,000 deaths in 2022, breast cancer is the fourth-leading cause of cancer death worldwide.⁵ In the U.S., it is estimated that there will be more than 310,000 new cases of breast cancer diagnosed in 2024. Breast cancer is the second leading cause of cancer death in women in the U.S.⁶

About Inluriyo^™ (imlunestrant) 
Inluriyo (imlunestrant) is an oral estrogen receptor antagonist that delivers continuous ER inhibition, including in ESR1-mutant cancers. The estrogen receptor (ER) is the key therapeutic target for patients with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2–) breast cancer. Inluriyo is a U.S. FDA approved oral prescription medicine. Inluriyo is also currently being studied in combination with abemaciclib for advanced breast cancer and as an adjuvant treatment in early breast cancer, including: NCT04975308, NCT05514054 and NCT04188548.

INDICATION FOR INLURIYO (imlunestrant)

INLURIYO is indicated for the treatment of adults with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, estrogen receptor-1 (ESR1)-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy.

IMPORTANT SAFETY INFORMATION FOR INLURIYO 

Warnings and Precautions — Embryo-Fetal Toxicity

Based on findings in animals and its mechanism of action, Inluriyo can cause fetal harm when administered to a pregnant woman. In an animal reproduction study, oral administration of imlunestrant to pregnant rats during the period of organogenesis led to embryo-fetal mortality and structural abnormalities at maternal exposures that were below the human exposure at the recommended dose based on area under the curve (AUC). Avoid the use of imlunestrant in pregnant women. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment with Inluriyo and for 1 week after the last dose.

Serious and Fatal Adverse Reactions 

Serious adverse reactions occurred in 10% of patients who received Inluriyo. Serious adverse reactions in >1% of patients included pleural effusion (1.2%). Fatal adverse reactions occurred in 1.8% of patients who received Inluriyo, including cardiac arrest, acute myocardial infarction, right ventricular failure, hypovolemic shock, and upper gastrointestinal hemorrhage (each 0.3%).

Most Common Adverse Reactions 

The most common adverse reactions (incidence ≥10%), including laboratory abnormalities, in patients who received Inluriyo were: hemoglobin decreased (30%), musculoskeletal pain (30%), calcium decreased (26%), neutrophils decreased (26%), AST increased (25%), fatigue (23%), diarrhea (22%), ALT increased (21%), triglycerides increased (21%), nausea (17%), platelets decreased (16%), constipation (10%), cholesterol increased (10%), and abdominal pain (10%).

Drug Interactions 

Imlunestrant is a CYP3A substrate. Avoid concomitant use of Inluriyo with strong CYP3A inhibitors. If concomitant use cannot be avoided, reduce the dosage of Inluriyo. Avoid concomitant use of Inluriyo with strong CYP3A inducers. If concomitant use cannot be avoided, increase the dosage of Inluriyo.

Imlunestrant inhibits both P-gp and BCRP. Avoid concomitant use unless otherwise recommended in the Prescribing Information for P-gp or BCRP substrates where minimal concentration changes may lead to serious adverse reactions.

Use in Specific Populations — Lactation 

Because of the potential for serious adverse reactions in the breastfed child, advise lactating women to not breastfeed during treatment with Inluriyo and for 1 week after the last dose.

Use in Specific Populations — Hepatic Impairment 

Reduce the dose of Inluriyo for patients with moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment. No dosage adjustment is recommended for patients with mild hepatic impairment (Child-Pugh A).

Inluriyo (imlunestrant) is available as 200 mg tablets.

Please click to access Prescribing Information for Inluriyo. 

IN HCP ISI M APP

About Verzenio (abemaciclib) 
Verzenio (abemaciclib) is approved to treat people with certain HR+, HER2- breast cancers in the adjuvant and advanced or metastatic settings.

Verzenio is an oral tablet taken twice daily and available in strengths of 50 mg, 100 mg, 150 mg, and 200 mg. Discovered and developed by Lilly researchers, Verzenio was first approved in 2017 and is currently authorized for use in more than 90 counties around the world. For full details on indicated uses of Verzenio in HR+, HER2- breast cancer, please see full Prescribing Information, available at www.Verzenio.com.

INDICATIONS FOR VERZENIO

VERZENIO is a kinase inhibitor indicated:

• in combination with endocrine therapy (tamoxifen or an aromatase inhibitor) for the adjuvant treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-positive, early breast cancer at high risk of recurrence.
• in combination with an aromatase inhibitor as initial endocrine-based therapy for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer.
• in combination with fulvestrant for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer with disease progression following endocrine therapy.
• as monotherapy for the treatment of adult patients with HR-positive, HER2-negative advanced or metastatic breast cancer with disease progression following endocrine therapy and prior chemotherapy in the metastatic setting.

IMPORTANT SAFETY INFORMATION FOR VERZENIO (abemaciclib)

Severe diarrhea associated with dehydration and infection occurred in patients treated with Verzenio. Across four clinical trials in 3691 patients, diarrhea occurred in 81 to 90% of patients who received Verzenio. Grade 3 diarrhea occurred in 8 to 20% of patients receiving Verzenio. Most patients experienced diarrhea during the first month of Verzenio treatment. The median time to onset of the first diarrhea event ranged from 6 to 8 days; and the median duration of Grade 2 and Grade 3 diarrhea ranged from 6 to 11 days and 5 to 8 days, respectively. Across trials, 19 to 26% of patients with diarrhea required a Verzenio dose interruption and 13 to 23% required a dose reduction.

Instruct patients to start antidiarrheal therapy, such as loperamide, at the first sign of loose stools, increase oral fluids, and notify their healthcare provider for further instructions and appropriate follow-up. For Grade 3 or 4 diarrhea, or diarrhea that requires hospitalization, discontinue Verzenio until toxicity resolves to ≤Grade 1, and then resume Verzenio at the next lower dose.

Neutropenia, including febrile neutropenia and fatal neutropenic sepsis, occurred in patients treated with Verzenio. Across four clinical trials in 3691 patients, neutropenia occurred in 37 to 46% of patients receiving Verzenio. A Grade ≥3 decrease in neutrophil count (based on laboratory findings) occurred in 19 to 32% of patients receiving Verzenio. Across trials, the median time to first episode of Grade ≥3 neutropenia ranged from 29 to 33 days, and the median duration of Grade ≥3 neutropenia ranged from 11 to 16 days. Febrile neutropenia has been reported in <1% of patients exposed to Verzenio across trials. Two deaths due to neutropenic sepsis were observed in MONARCH 2. Inform patients to promptly report any episodes of fever to their healthcare provider.

Monitor complete blood counts prior to the start of Verzenio therapy, every 2 weeks for the first 2 months, monthly for the next 2 months, and as clinically indicated. Dose interruption, dose reduction, or delay in starting treatment cycles is recommended for patients who develop Grade 3 or 4 neutropenia.

Severe, life-threatening, or fatal interstitial lung disease (ILD) or pneumonitis can occur in patients treated with Verzenio and other CDK4/6 inhibitors. In Verzenio-treated patients in EBC (monarchE), 3% of patients experienced ILD or pneumonitis of any grade: 0.4% were Grade 3 or 4 and there was one fatality (0.1%). In Verzenio-treated patients in MBC (MONARCH 1, MONARCH 2, MONARCH 3), 3.3% of Verzenio-treated patients had ILD or pneumonitis of any grade: 0.6% had Grade 3 or 4, and 0.4% had fatal outcomes. Additional cases of ILD or pneumonitis have been observed in the postmarketing setting, with fatalities reported.

Monitor patients for pulmonary symptoms indicative of ILD or pneumonitis. Symptoms may include hypoxia, cough, dyspnea, or interstitial infiltrates on radiologic exams. Infectious, neoplastic, and other causes for such symptoms should be excluded by means of appropriate investigations. Dose interruption or dose reduction is recommended in patients who develop persistent or recurrent Grade 2 ILD or pneumonitis. Permanently discontinue Verzenio in all patients with Grade 3 or 4 ILD or pneumonitis.

Grade ≥ 3 increases in alanine aminotransferase (ALT) (2 to 6%) and aspartate aminotransferase (AST) (2 to 3%) were reported in patients receiving Verzenio. Across three clinical trials in 3559 patients (monarchE, MONARCH 2, MONARCH 3), the median time to onset of Grade ≥3 ALT increases ranged from 57 to 87 days and the median time to resolution to Grade <3 was 13 to 14 days. The median time to onset of Grade ≥3 AST increases ranged from 71 to 185 days and the median time to resolution to Grade <3 ranged from 11 to 15 days.

Monitor liver function tests (LFTs) prior to the start of Verzenio therapy, every 2 weeks for the first 2 months, monthly for the next 2 months, and as clinically indicated. Dose interruption, dose reduction, dose discontinuation, or delay in starting treatment cycles is recommended for patients who develop persistent or recurrent Grade 2, or any Grade 3 or 4 hepatic transaminase elevation.

Venous thromboembolic events (VTE) were reported in 2 to 5% of patients across three clinical trials in 3559 patients treated with Verzenio (monarchE, MONARCH 2, MONARCH 3). VTE included deep vein thrombosis, pulmonary embolism, pelvic venous thrombosis, cerebral venous sinus thrombosis, subclavian and axillary vein thrombosis, and inferior vena cava thrombosis. In clinical trials, deaths due to VTE have been reported in patients treated with Verzenio.

Verzenio has not been studied in patients with early breast cancer who had a history of VTE. Monitor patients for signs and symptoms of venous thrombosis and pulmonary embolism and treat as medically appropriate. Dose interruption is recommended for EBC patients with any grade VTE and for MBC patients with a Grade 3 or 4 VTE.

Verzenio can cause fetal harm when administered to a pregnant woman, based on findings from animal studies and the mechanism of action. In animal reproduction studies, administration of abemaciclib to pregnant rats during the period of organogenesis caused teratogenicity and decreased fetal weight at maternal exposures that were similar to the human clinical exposure based on area under the curve (AUC) at the maximum recommended human dose. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with Verzenio and for 3 weeks after the last dose. Based on findings in animals, Verzenio may impair fertility in males of reproductive potential. There are no data on the presence of Verzenio in human milk or its effects on the breastfed child or on milk production. Advise lactating women not to breastfeed during Verzenio treatment and for at least 3 weeks after the last dose because of the potential for serious adverse reactions in breastfed infants.

The most common adverse reactions (all grades, ≥10%) observed in monarchE for Verzenio plus tamoxifen or an aromatase inhibitor vs tamoxifen or an aromatase inhibitor, with a difference between arms of ≥2%, were diarrhea (84% vs 9%), infections (51% vs 39%), neutropenia (46% vs 6%), fatigue (41% vs 18%), leukopenia (38% vs 7%), nausea (30% vs 9%), anemia (24% vs 4%), headache (20% vs 15%), vomiting (18% vs 4.6%), stomatitis (14% vs 5%), lymphopenia (14% vs 3%), thrombocytopenia (13% vs 2%), decreased appetite (12% vs 2.4%), ALT increased (12% vs 6%), AST increased (12% vs 5%), dizziness (11% vs 7%), rash (11% vs 4.5%), and alopecia (11% vs 2.7 %).

The most frequently reported ≥5% Grade 3 or 4 adverse reaction that occurred in the Verzenio arm vs the tamoxifen or an aromatase inhibitor arm of monarchE were neutropenia (19.6% vs 1%), leukopenia (11% vs <1%), diarrhea (8% vs 0.2%), and lymphopenia (5% vs <1%).

Lab abnormalities (all grades; Grade 3 or 4) for monarchE in ≥10% for Verzenio plus tamoxifen or an aromatase inhibitor with a difference between arms of ≥2% were increased serum creatinine (99% vs 91%; .5% vs <.1%), decreased white blood cells (89% vs 28%; 19.1% vs 1.1%), decreased neutrophil count (84% vs 23%; 18.7% vs 1.9%), anemia (68% vs 17%; 1% vs .1%), decreased lymphocyte count (59% vs 24%; 13.2 % vs 2.5%), decreased platelet count (37% vs 10%; .9% vs .2%), increased ALT (37% vs 24%; 2.6% vs 1.2%), increased AST (31% vs 18%; 1.6% vs .9%), and hypokalemia (11% vs 3.8%; 1.3% vs 0.2%).

The most common adverse reactions (all grades, ≥10%) observed in MONARCH 3 for Verzenio plus anastrozole or letrozole vs anastrozole or letrozole, with a difference between arms of ≥2%, were diarrhea (81% vs 30%), fatigue (40% vs 32%), neutropenia (41% vs 2%), infections (39% vs 29%), nausea (39% vs 20%), abdominal pain (29% vs 12%), vomiting (28% vs 12%), anemia (28% vs 5%), alopecia (27% vs 11%), decreased appetite (24% vs 9%), leukopenia (21% vs 2%), creatinine increased (19% vs 4%), constipation (16% vs 12%), ALT increased (16% vs 7%), AST increased (15% vs 7%), rash (14% vs 5%), pruritus (13% vs 9%), cough (13% vs 9%), dyspnea (12% vs 6%), dizziness (11% vs 9%), weight decreased (10% vs 3.1%), influenza-like illness (10% vs 8%), and thrombocytopenia (10% vs 2%).

The most frequently reported ≥5% Grade 3 or 4 adverse reactions that occurred in the Verzenio arm vs the placebo arm of MONARCH 3 were neutropenia (22% vs 1%), diarrhea (9% vs 1.2%), leukopenia (7% vs <1%)), increased ALT (6% vs 2%), and anemia (6% vs 1%).

Lab abnormalities (all grades; Grade 3 or 4) for MONARCH 3 in ≥10% for Verzenio plus anastrozole or letrozole with a difference between arms of ≥2% were increased serum creatinine (98% vs 84%; 2.2% vs 0%), decreased white blood cells (82% vs 27%; 13% vs 0.6%), anemia (82% vs 28%; 1.6% vs 0%), decreased neutrophil count (80% vs 21%; 21.9% vs 2.6%), decreased lymphocyte count (53% vs 26%; 7.6% vs 1.9%), decreased platelet count (36% vs 12%; 1.9% vs 0.6%), increased ALT (48% vs 25%; 6.6% vs 1.9%), and increased AST (37% vs 23%; 3.8% vs 0.6%).

The most common adverse reactions (all grades, ≥10%) observed in MONARCH 2 for Verzenio plus fulvestrant vs fulvestrant, with a difference between arms of ≥2%, were diarrhea (86% vs 25%), neutropenia (46% vs 4%), fatigue (46% vs 32%), nausea (45% vs 23%), infections (43% vs 25%), abdominal pain (35% vs 16%), anemia (29% vs 4%), leukopenia (28% vs 2%), decreased appetite (27% vs 12%), vomiting (26% vs 10%), headache (20% vs 15%), dysgeusia (18% vs 2.7%), thrombocytopenia (16% vs 3%), alopecia (16% vs 1.8%), stomatitis (15% vs 10%), ALT increased (13% vs 5%), pruritus (13% vs 6%), cough (13% vs 11%), dizziness (12% vs 6%), AST increased (12% vs 7%), peripheral edema (12% vs 7%), creatinine increased (12% vs <1%), rash (11% vs 4.5%), pyrexia (11% vs 6%), and weight decreased (10% vs 2.2%).

The most frequently reported ≥5% Grade 3 or 4 adverse reactions that occurred in the Verzenio arm vs the placebo arm of MONARCH 2 were neutropenia (25% vs 1%), diarrhea (13% vs 0.4%), leukopenia (9% vs 0%), anemia (7% vs 1%), and infections (5.7% vs 3.5%).

Lab abnormalities (all grades; Grade 3 or 4) for MONARCH 2 in ≥10% for Verzenio plus fulvestrant with a difference between arms of ≥2% were increased serum creatinine (98% vs 74%; 1.2% vs 0%), decreased white blood cells (90% vs 33%; 23.7% vs .9%), decreased neutrophil count (87% vs 30%; 32.5% vs 4.2%), anemia (84% vs 34%; 2.6% vs .5%), decreased lymphocyte count (63% vs 32%; 12.2% vs 1.8%), decreased platelet count (53% vs 15%; 2.1% vs 0%), increased ALT (41% vs 32%; 4.6% vs 1.4%), and increased AST (37% vs 25%; 3.9% vs 4.2%).

The  most common adverse reactions (all grades, ≥10%) observed in MONARCH 1 with Verzenio were diarrhea (90%), fatigue (65%), nausea (64%), decreased appetite (45%), abdominal pain (39%), neutropenia (37%), vomiting (35%), infections (31%), anemia (25%), thrombocytopenia (20%), headache (20%), cough (19%), constipation (17%), leukopenia (17%), arthralgia (15%), dry mouth (14%), weight decreased (14%), stomatitis (14%), creatinine increased (13%), alopecia (12%), dysgeusia (12%), pyrexia (11%), dizziness (11%), and dehydration (10%).

The most frequently reported ≥5% Grade 3 or 4 adverse reactions from MONARCH 1 with Verzenio were diarrhea (20%), neutropenia (24%), fatigue (13%), and leukopenia (5%).

Lab abnormalities (all grades; Grade 3 or 4) for MONARCH 1 with Verzenio were increased serum creatinine (99%; .8%), decreased white blood cells (91%; 28%), decreased neutrophil count (88%; 26.6%), anemia (69%; 0%), decreased lymphocyte count (42%; 13.8%), decreased platelet count (41%; 2.3%), increased ALT (31%; 3.1%), and increased AST (30%; 3.8%).

Strong and moderate CYP3A inhibitors increased the exposure of abemaciclib plus its active metabolites to a clinically meaningful extent and may lead to increased toxicity. Avoid concomitant use of ketoconazole. Ketoconazole is predicted to increase the AUC of abemaciclib by up to 16-fold. In patients with recommended starting doses of 200 mg twice daily or 150 mg twice daily, reduce the Verzenio dose to 100 mg twice daily with concomitant use of strong CYP3A inhibitors other than ketoconazole. In patients who have had a dose reduction to 100 mg twice daily due to adverse reactions, further reduce the Verzenio dose to 50 mg twice daily with concomitant use of strong CYP3A inhibitors. If a patient taking Verzenio discontinues a strong CYP3A inhibitor, increase the Verzenio dose (after 3 to 5 half-lives of the inhibitor) to the dose that was used before starting the inhibitor. With concomitant use of moderate CYP3A inhibitors, monitor for adverse reactions and consider reducing the Verzenio dose in 50 mg decrements. Patients should avoid grapefruit products.

Avoid concomitant use of strong or moderate CYP3A inducers and consider alternative agents. Coadministration of strong or moderate CYP3A inducers decreased the plasma concentrations of abemaciclib plus its active metabolites and may lead to reduced activity.

With severe hepatic impairment (Child-Pugh C), reduce the Verzenio dosing frequency to once daily. The pharmacokinetics of Verzenio in patients with severe renal impairment (CLcr <30 mL/min), end stage renal disease, or in patients on dialysis is unknown. No dosage adjustments are necessary in patients with mild or moderate hepatic (Child-Pugh A or B) and/or renal impairment (CLcr ≥30-89 mL/min).

Please see full Prescribing Information and Patient Information for Verzenio.

AL HCP ISI 12OCT2021

About Lilly 
Lilly is a medicine company turning science into healing to make life better for people around the world. We've been pioneering life-changing discoveries for nearly 150 years, and today our medicines help tens of millions of people across the globe. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world's most significant health challenges: redefining diabetes care; treating obesity and curtailing its most devastating long-term effects; advancing the fight against Alzheimer's disease; providing solutions to some of the most debilitating immune system disorders; and transforming the most difficult-to-treat cancers into manageable diseases. With each step toward a healthier world, we're motivated by one thing: making life better for millions more people. That includes delivering innovative clinical trials that reflect the diversity of our world and working to ensure our medicines are accessible and affordable. To learn more, visit Lilly.com and Lilly.com/news, or follow us on Facebook, Instagram, and LinkedIn. P-LLY

© Lilly USA, LLC 2025. ALL RIGHTS RESERVED.

MSK Disclosure: Dr. Jhaveri has financial interests related to Eli Lilly and Company

Trademarks and Trade Names 
All trademarks or trade names referred to in this press release are the property of the company, or, to the extent trademarks or trade names belonging to other companies are references in this press release, the property of their respective owners. Solely for convenience, the trademarks and trade names in this press release are referred to without the ^® and ™ symbols, but such references should not be construed as any indicator that the company or, to the extent applicable, their respective owners will not assert, to the fullest extent under applicable law, the company's or their rights thereto. We do not intend the use or display of other companies' trademarks and trade names to imply a relationship with, or endorsement or sponsorship of us by, any other companies.

Cautionary Statement Regarding Forward-Looking Statements
This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about Verzenio (abemaciclib) as a potential treatment for people with certain types of early breast cancer and Inluriyo (imlunestrant) as a treatment for people with certain types of breast cancer. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of drug research, development, and commercialization. Among other things, there is no guarantee that planned or ongoing studies will be completed as planned, that future study results will be consistent with study results to date, that any of these therapies will prove to be a safe and effective treatment or receive regulatory approval, or that Lilly will execute its strategy as expected. For further discussion of these and other risks and uncertainties that could cause actual results to differ from Lilly's expectations, see Lilly's Form 10-K and Form 10-Q filings with the United States Securities and Exchange Commission. Except as required by law, Lilly undertakes no duty to update forward-looking statements to reflect events after the date of this release.

References
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3. Metastatic Breast Cancer Network. 13 Facts about Metastatic Breast Cancer. http://www.mbcn.org/13-facts-about-metastatic-breast-cancer/. Accessed July 9, 2024. 
4. American Cancer Society. Breast Cancer Facts & Figures 2022-2024. Atlanta: American Cancer Society, Inc. 2022. https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/breast-cancer-facts-and-figures/2022-2024-breast-cancer-fact-figures-acs.pdf. Accessed July 9, 2024. 
5. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229-263.
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